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Histological Grade (histological + grade)
Kinds of Histological Grade Selected AbstractsIntraoperative evaluation of sentinel lymph nodes in breast carcinoma by imprint cytology, frozen section and rapid immunohistochemistryDIAGNOSTIC CYTOPATHOLOGY, Issue 12 2009Sharma Upender M.D. Abstract Sentinel lymph nodes (SLN) isolated in 40 patients of breast carcinoma (stage T1/T2) were evaluated intraoperatively by imprint cytology and frozen section. Rapid immunohistochemistry (IHC) was done in cases where both imprint smears and frozen sections were negative for any metastatic tumor deposits. The results of these different techniques were compared with postoperative paraffin sections taken as "Gold Standard." Nottingham modification of Bloom Richardson scoring system was used for grading the tumors. Further, the correlation of the SLN status with tumor size, grade, and lymphovascular invasion was studied. The sensitivity, specificity, and overall accuracy of imprint cytology were 91.7, 100, and 95% respectively, and those of the frozen section were 95.8, 100, and 97.5% respectively. Examination of multiple serial sections improved the sensitivity and overall accuracy of frozen section. Results of intraoperative rapid IHC were equivalent to final paraffin sections. Histological grade and lymphovascular invasion were in direct correlation with SLN metastasis (P < 0.05). The risk of lymphovascular invasion increased from 22.2% in grade I tumors to 85.7% in grade III tumors. SLN biopsy is a reliable method to evaluate the status of the axillary lymph nodes. Imprint cytology can be used reliably where the facility of frozen section is not available. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Risk factors for lymph node metastasis in clinically node-negative penile cancer patientsINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2009Aravind Ramkumar Objectives: To analyze the effects of pathological T stage, grade, extent of surgery for primary tumor, and age group on the risk of developing lymph node metastasis in clinically node-negative penile cancer patients. Methods: We performed a retrospective analysis of 200 clinically node-negative penile cancer patients who were kept under surveillance, after treatment of the primary tumor in our institution. The primary outcome parameter was cytologically or histologically proven lymph node metastasis. Logistic regression analysis was used to compute odds ratios in univariate and multivariate settings. Results: Lymph node metastasis occurred in 31 patients at a median time of three months. Histological grade 3 and grade 2 tumors had a statistically significant increased odds ratio for lymph node metastasis, (7.1[P < 0.001] and 2.7 [P = 0.04], respectively), compared with grade 1 tumors. Although increasing pT stage was associated with increasing odds ratios, the differences were not statistically significant. Nor did the extent of surgery of the primary tumor or the age group significantly influence the risk of developing lymph node metastasis. Conclusions: Histological grade is the most significant parameter influencing the risk of lymph node metastasis in clinically node-negative penile cancer patients on surveillance. Patients with grade 3 and grade 2 tumors may benefit from elective inguinal lymphadenectomy. [source] Combined histology and molecular biology for diagnosis of early stage gastric MALT lymphomaJOURNAL OF DIGESTIVE DISEASES, Issue 1 2006Zhi Hui YI OBJECTIVE: To establish a sequential diagnostic procedure of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and provide evidence for selected optimal cases to be treated in the early stage. METHODS: Thirty-one cases of gastric lymphoid hyperplasia (GLH) were selected and multiple investigations including histology, protein level, DNA and chromosome levels, combined with clinical follow-up were performed. Histological grade was according to Isaacson's criteria of GLH; CD20, UCHL-1 (CD45RO), anti-kappa (,), anti-lambda (,) and Ki-67 were used for immunohistochemical staining; semi-nested polymerase chain reaction (PCR) was used to detect IgH gene rearrangement and reverse-transcription PCR (RT-PCR) was used to detect API2-MALT1 fusion of the chromosome translocation t(11;18)(q21;q21). Twenty-nine cases underwent eradication therapy for Helicobacter pylori. Changes in histological grade, endoscopic appearance, expression of Ki-67 and IgH gene rearrangement were compared after eradication treatment. RESULTS: Of the 31 cases of GLH with predominant chronic gastritis and gastric ulcer most were histological grade 2 and 3. Only one case had , light chain restriction and 10 cases had monoclonal IgH gene rearrangement. Expression of Ki-67 and monoclonal IgH gene rearrangement were significantly increased with increased lymphoid hyperplasia (P < 0.05). Two cases had API2-MALT1 fusion. Helicobacter pylori was eradicated in 25 cases and another course of treatment had to be given in 4 cases. All cases were followed up for 1.5,37 months. Of the 27 successful eradication cases, 18 showed complete regression both histologically and endoscopically, 4 had partial regression and 7 were unchanged. CONCLUSIONS: A sequential diagnostic procedure based on histology, expression of Ki-67 combined with clonality of IgH rearrangement and API2-MALT1 fusion helps to diagnosis of early stage gastric MALT lymphoma and choose the best treatment strategy. [source] EFFECT OF RESECTION AND OUTCOME IN PATIENTS WITH RETROPERITONEAL SARCOMAANZ JOURNAL OF SURGERY, Issue 6 2006Antonio Chiappa Background: A consecutive series of 47 patients with retroperitoneal sarcoma (RPS) were resected and prospectively followed. Method: Between July 1994 and March 2005, 47 patients (24 men, 23 women; mean age, 56 years; range, 17,82 years) were evaluated. Results: A total of 23 patients had primary RPS and 24 patients had recurrent RPS. A total of 30 out of 47 patients (64%) underwent removal of contiguous intra-abdominal organs. The peroperative mortality was nil and significant preoperative complications occurred in eight cases only (17%). High tumour grade and incomplete resection were significant variables for a worse survival in all 47 patients, both in the univariate and multivariate analyses (P = 0.008 and P = 0.016, respectively). Among 28 radically resected patients, only histological grade affected overall survival (90% 5-year survival for low-grade tumour vs 26% 5-year survival for high-grade tumour; P = 0.006) with a similar effect noted for disease-free survival. Conclusions: Histological grade was the only factor that affected overall and disease-free survival for RPS tumours. An aggressive surgical approach in both primary and recurrent RPS is associated with long-term survival. [source] The acquisition time of infection: a determinant of the severity of hepatitis C virus-related liver disease in renal transplant patientsCLINICAL TRANSPLANTATION, Issue 5 2009H. Töz Abstract:, Background:, The aim of this study was to compare the clinical and histopathological course of HCV infection acquired before and during or after renal transplantation. Methods:, According to HCV status, 197 RT patients were divided into three groups. At the time of RT, anti-HCV antibody was positive in 47 patients (pre-RT HCV group). In 27 patients, in whom anti-HCV negative at the time of RT, anti-HCV and/or HCV RNA was found to be positive following an ALT elevation episode after RT (post-RT HCV group). Both anti-HCV and HCV RNA were negative at all times in remaining 123 patients (control group). Results:, Liver biopsy was performed in 31 of 47 patients in pre-RT and 24 of 27 in post-RT HCV group after RT. Duration of follow-up was similar in all groups with a mean of 7.1 ± 4.0 yr. Ascites and encephalopathy were seen in only post-RT HCV group (22%). Histological grade (6.5 ± 2.7 vs. 4.1 ± 1.4) and stage (2.0 ± 1.5 vs. 0.8 ± 0.8) was significantly severe in post-RT HCV group (p < 0.01). Three patients died due to liver failure in post-RT HCV group. Conclusions:, HCV infection acquired during or after RT shows a severe and rapidly progressive clinicopathological course, which is significantly different from pre-transplant anti-HCV positive patients. [source] Predictive value of renal histological changes for postoperative renal function improvement in children with congenital ureteropelvic junction stenosisINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2002Ahmet Erbagci Abstract Background: The aim of this study was to evaluate the relationship between renal function, as measured by diuretic radionuclide renography, and the outcome of pyeloplasty. A study was designed to evaluate renal parenchymal biopsy specimens derived from children undergoing corrective surgery for ureteropelvic junction (UPJ) stenosis, and compare these to preoperative and postoperative renal function status. Methods: Thirty-five children with congenital unilateral UPJ stenosis were evaluated. In addition to all conventional diagnostic procedures for UPJ stenosis, differential renal functional (DRF) activity was assessed in each of these children by obtaining 99mTc diethylenetriaminepentaacetic acid renogram curves. All children underwent dismembered pyeloplasty, and follow-up renogram evaluation was conducted 6 and 12 months after surgical repair. Biopsy specimens from renal cortical regions obtained during the surgical correction of UPJ stenosis were evaluated, and changes in renal histology were graded from I to V according to their severity. Spearman's correlation test was used to compare the histological evaluation results and the basal, 6- and 12-month follow-up DRF findings. A Wilcoxon paired test was used to evaluate statistical differences between values. Results: The findings showed a positive correlation between the severity of histological changes and DRF activity. All kidneys (22) with a DRF activity value of < 40% preoperatively demonstrated at least grade III changes when biopsy specimens were examined. Of children with a DRF activity value > 40% (13), only three showed severe histological changes. Histological grades were correlated between basal (r = ,0.4; P = 0.019), 6-month (r = 0.54; P = 0.002) and 12-month (r = 0.54; P = 0.02) findings. In the Wilcoxon paired test, there was a statistically significant difference between basal and 6-month values (P < 0.05), and also between basal and 12-month values (P < 0.01). There was no statistically significant difference between 6- and 12-month values (P > 0.20). Conclusion: Comparative evaluation of postoperative renal function with DRF activity and renal parenchymal histological alterations revealed a close correlation in terms of renal function improvement potential following reconstructive surgery in children with UPJ stenosis. [source] Validation of Diagnostic Tests for Helicobacter pylori with Regard to Grade of Atrophic Gastritis and/or Intestinal MetaplasiaHELICOBACTER, Issue 6 2009Cheol Min Shin Abstract Background and Aims:, To evaluate the validity of the biopsy-based tests (histology, culture, and urease test) and serology in detecting current Helicobacter pylori infection against a background of atrophic gastritis (AG) or intestinal metaplasia (IM). Methods:,Helicobacter pylori infection was diagnosed in 651 subjects, using the predefined gold standard for H. pylori tests. The sensitivity, specificity, and positive and negative predictive values of culture, CLOtest, histology (Giemsa stain), and serology were calculated with regard to the histological grade of AG and IM. The level of serum pepsinogen (PG) I and II was also measured as a marker for the presence of AG. Results:, In the study population (n = 651), sensitivity and specificity, respectively, were as follows: culture, 56.2 and 100%; histology, 93.0 and 94.0%; CLOtest, 80.4 and 96.7%; serology, 96.0 and 67.5%. If the analysis is limited to those without AG or IM (n = 158) or to those younger than 40 years (n = 69), all tests, except for culture, had a sensitivity and specificity >90%. The sensitivity of CLOtest and the specificity of serology markedly decreased with progression of AG and IM, and serology was less specific in the presence of AG, as determined by a PG I/II ratio ,4.1 (specificity, 83.7% vs 40.7% in PG I/II >4.1 and ,4.1, respectively). Conclusions:, Any one of biopsy-based tests or serology was found to be excellent for identifying current H. pylori infection among individuals without AG or IM and/or younger patients (<40 years). However, a combination of at least two tests is necessary in the clinical setting of AG or IM. [source] Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosisHISTOPATHOLOGY, Issue 6 2010Maria S Tretiakova Tretiakova M S, Shabani-Rad M T, Guggisberg K, Hart J, Anders R A & Gao Z-h (2010) Histopathology,56, 683,693 Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosis Aims:, To compare the expression of genes involved in p53, Wnt/,-catenin, and retinoblastoma (Rb) 1 pathways between cirrhosis-associated hepatocellular carcinoma (HCC-C) and hepatocellular carcinoma arising in non-cirrhotic liver (HCC-NC). Methods and results:, The gene expression profile was analysed using oligo-DNA arrays, and then validated at protein level in a tissue microarray using immunohistochemistry. Compared with their background non-neoplastic liver tissue, HCC-C showed a significantly higher rate of p53, ,-catenin (protein only) and cyclin D1 expression, whereas HCC-NC showed a significantly higher rate of p21Waf1/cip1 and p27Kip1 expression. HCC-C had a significantly higher rate of p53 expression and a significantly lower rate of p21waf1/cip1 expression than HCC-NC. There was no statistically significant association between the expression of genetic markers and tumour histological grade, underlying aetiology, or lymphovascular invasion. Aberrant ,-catenin expression was more commonly seen in single tumours in comparison with multiple tumours. Increased p16INK4 and p21waf1/cip1 expression was more commonly observed in large-sized tumours (>50 mm) than small-sized tumours. Conclusions:, Alteration of the p53 pathway plays a more important role in the pathogenesis of HCC-C, whereas alterations in cell cycle regulators p21waf1/cip1 and p27Kip1 play a more important role in the pathogenesis of HCC-NC. [source] Correlation of hypoxic signalling to histological grade and outcome in cartilage tumoursHISTOPATHOLOGY, Issue 5 2010Stephane Boeuf Boeuf S, Bovée J V M G, Lehner B, Hogendoorn P C W & Richter W (2010) Histopathology56, 641,651 Correlation of hypoxic signalling to histological grade and outcome in cartilage tumours Aims:, The molecular mechanisms underlying the progression of central chondrosarcoma are so far poorly understood. The aim of this study was to identify genes involved in the progression of these tumours by comparison of gene expression and correlation of expression profiles to histological grade and clinical outcome. Methods and results:, Array-based gene expression profiling of 19 chondrosarcoma samples was performed. Beside differences in the expression of cartilage matrix molecules, high-grade chondrosarcoma showed enhanced expression of the matrix metalloproteinase MMP-2 and of the hypoxia-inducible molecule galectin 1. Immunohistochemical analysis of galectin 1 and of further hypoxia-associated proteins was performed on 68 central and peripheral tumour samples. Hypoxia-inducible factor 1, (HIF-1,) activation was significantly elevated in high-grade central chondrosarcoma. A negative correlation of carbonic anhydrase IX expression to metastasis-free survival was independent of histological grade. Conclusions:, The expression patterns identified in this study point towards a substantial role for angiogenic and hypoxic signalling in chondrosarcoma progression. The constitutive activation of the transcription factor HIF-1, in high-grade chondrosarcoma could play a central role in the regulation of cell metabolism and vascularization in these tumours and may, for this reason, represent a potential target for chondrosarcoma therapy. [source] Down-regulation of ATBF1 is a major inactivating mechanism in hepatocellular carcinomaHISTOPATHOLOGY, Issue 5 2008C J Kim Aims:, ,-Fetoprotein (AFP) is frequently detected in hepatocellular carcinomas (HCCs) and AT motif binding factor 1 (ATBF1) down-regulates AFP gene expression in hepatic cells. The ATBF1 gene also inhibits cell growth and differentiation, and altered gene expression is associated with malignant transformation. The aim was to investigate the potential role of the ATBF1 gene in HCCs. Methods and results:, Somatic mutations, allelic loss and hypermethylation of the ATBF1 gene were analysed in 76 sporadic HCCs. The level of ATBF-1 mRNA expression was analysed using quantitative real-time reverse transcriptase-polymerase chain reaction. Genetic studies of the ATBF1 gene revealed absence of somatic mutation in the hotspot region and 15 (25%) of 60 informative cases showed allelic loss at the ATBF1 locus. Hypermethylation in the intron 1 region of the ATBF1 gene was detected in only one case. Interestingly, ATBF1 mRNA expression in HCCs was significantly reduced in 55 (72.4%) samples compared with the corresponding surrounding liver tissues. Reduced expression was not statistically associated with clinicopathological parameters including stage, histological grade, infective virus type, and serum ,-fetoprotein level. Conclusions:, The ATBF1 gene may contribute to the development of HCCs via transcriptional down-regulation of mRNA expression, but not by genetic or epigenetic alterations. [source] Triple negative tumours: a critical reviewHISTOPATHOLOGY, Issue 1 2008J S Reis-Filho Breast cancer is a heterogeneous disease that encompasses several distinct entities with remarkably different biological characteristics and clinical behaviour. Currently, breast cancer patients are managed according to algorithms based on a constellation of clinical and histopathological parameters in conjunction with assessment of hormone receptor (oestrogen and progesterone receptor) status and HER2 overexpression/gene amplification. Although effective tailored therapies have been developed for patients with hormone receptor-positive or HER2+ disease, chemotherapy is the only modality of systemic therapy for patients with breast cancers lacking the expression of these markers (triple-negative cancers). Recent microarray expression profiling analyses have demonstrated that breast cancers can be systematically characterized into biologically and clinically meaningful groups. These studies have led to the re-discovery of basal-like breast cancers, which preferentially show a triple-negative phenotype. Both triple-negative and basal-like cancers preferentially affect young and African-American women, are of high histological grade and have more aggressive clinical behaviour. Furthermore, a significant overlap between the biological and clinical characteristics of sporadic triple-negative and basal-like cancers and breast carcinomas arising in BRCA1 mutation carriers has been repeatedly demonstrated. In this review, we critically address the characteristics of basal-like and triple-negative cancers, their similarities and differences, their response to chemotherapy as well as strategies for the development of novel therapeutic targets for these aggressive types of breast cancer. In addition, the possible mechanisms are discussed leading to BRCA1 pathway dysfunction in sporadic triple-negative and basal-like cancers and animal models for these tumour types. [source] HMG-CoA reductase expression in breast cancer is associated with a less aggressive phenotype and influenced by anthropometric factorsINTERNATIONAL JOURNAL OF CANCER, Issue 5 2008Signe Borgquist Abstract Although several studies have reported on the anti-tumoural properties exerted by 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR) inhibitors (statins), the in vivo expression of HMG-CoAR in human cancer has been considerably less investigated. In our study, we examined the immunohistochemical expression of HMG-CoAR in 511 incident breast cancers within the Malmö Diet and Cancer Study in order to explore its relationship to established clinicopathological and tumour biological parameters. Furthermore, the potential influence of estrogen exposure on HMG-CoAR expression was assessed by performing Cox's proportional hazards analyses of the relationship between the use of hormone replacement therapy (HRT), obesity (waist circumference) and tumour-cell specific HMG-CoAR expression. We found that HMG-CoAR was present in various fractions and intensities in the cytoplasm, sometimes with a membranous pattern, but not in the tumour cell nuclei. The expression of HMG-CoAR was associated with a smaller tumour size (p = 0.02), low histological grade (p = 0.001), low Ki67 index (p = 0.004), ER,+ (p = 0.02), ER,+ (p = 0.005), and high p27 expression (p = <0.001). The incidence of tumours with a high HMG-CoAR-expression was increased among HRT-users, although this was not statistically significant in a heterogeneity analysis. Obesity was significantly associated with a high HMG-CoAR expression assessed both as a high (>50%) fraction of positive cells (relative risk: 2.06; 95% confidence interval: 1.20,3.51), and a strong staining intensity (2.33: 1.08,5.02). In summary, we demonstrate that HMG-CoAR is differentially expressed in breast cancer and that a high expression is associated with prognostically favourable tumour parameters. Moreover, estrogen related life-style and anthropometric factors might indeed regulate HMG-CoAR expression. © 2008 Wiley-Liss, Inc. [source] Regional DNA hypermethylation and DNA methyltransferase (DNMT) 1 protein overexpression in both renal tumors and corresponding nontumorous renal tissuesINTERNATIONAL JOURNAL OF CANCER, Issue 2 2006Eri Arai Abstract To evaluate the significance of altered DNA methylation during renal tumorigenesis, tumorous tissues (T) and corresponding nontumorous renal tissues (N) from 94 patients with renal tumors, and normal renal tissues (C) from 16 patients without renal tumors were investigated. DNA methylation status on CpG islands of the p16, human MutL homologue 1 (hMLH1), von-Hippel Lindau (VHL) and thrombospondin-1 (THBS-1) genes and the methylated in tumor (MINT) -1, -2, -12, -25 and -31 clones and DNA methyltransferase (DNMT) 1 expression were examined by bisulfite modification and immunohistochemistry, respectively. The average number of methylated CpG islands was significantly higher in N than in C, and was even higher in T. The average number of methylated CpG islands in N was significantly correlated with a higher histological grade of corresponding conventional renal cell carcinomas (RCCs). The average number of methylated CpG islands in RCCs was significantly correlated with macroscopic configuration with extranodular or multinodular growth, higher histological grade, infiltrating growth pattern and vascular involvement. The recurrence-free survival rate of patients with RCCs showing accumulation of DNA methylation was significantly lower than that of patients not showing this feature. The incidence of nuclear immunoreactivity for DNMT1 tended to be higher in proximal tubules from N than in those from C, and was significantly higher in RCCs. From the viewpoint of altered DNA methylation, N is at the precancerous stage, and N showing accumulation of DNA methylation may generate more malignant RCCs. Regional DNA hypermethylation may be associated with renal tumorigenesis from a precancerous condition to malignant progression and become a predictor of patient prognosis. © 2006 Wiley-Liss, Inc. [source] Impact of thrombocytosis and C-reactive protein elevation on the prognosis for patients with renal cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2006KEIICHI ITO Aim: C-reactive protein (CRP) elevation is reportedly a prognostic factor in patients with renal cell carcinoma (RCC). Thrombocytosis has recently been reported also to be a prognostic factor in RCC and, like CRP, to be related to inflammatory cytokines such as interleukin-6. The aim of this study was to evaluate the importance of both thrombocytosis and CRP elevation in tumor recurrence and prognosis for patients with RCC. Methods: The clinical records of 178 patients who underwent radical nephrectomy were reviewed. Thrombocytosis was defined as a platelet count ,350 000/mm3, and CRP elevation was defined as a CRP level ,1.0 mg/dL. Disease-free survival and cause-specific survival rates were calculated. Independent predictors for recurrence and prognosis were determined. Results: Patients with thrombocytosis and patients with elevated CRP levels had significantly higher pathological T stage, clinical stage, tumor size, histological grade, and percentage of microvascular invasion than did patients without THC and patients with CRP levels <1.0 mg/dL, respectively. There was a significant correlation between platelet counts and CRP levels. Multivariate analysis showed that distant metastasis, tumor size, grade 3 components, and CRP elevation were independent predictors for prognosis but thrombocytosis was not. In N0M0 RCC patients, tumor size, microvascular invasion, and CRP elevation were independent predictors for recurrence. CRP elevation and tumor size were independent predictors for prognosis. Conclusions: Platelet count and CRP level are strongly correlated in patients with RCC, but only CRP elevation is an independent predictor for recurrence and prognosis. [source] Serum calcitonin gene-related peptide levels in untreated prostate cancer patientsINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2006KAZUMI SUZUKI Background:, The role of calcitonin gene-related peptide (CGRP) in prostate cancer has not been fully understood. Moreover, the serum CGRP level in prostate cancer patients has never been reported. We measured the serum CGRP levels in untreated prostate cancer patients to elucidate its clinical significance. Materials and methods:, We used 36 serum samples from prostate cancer patients. All patients had never received any treatment. Serum CGRP was measured by immunoradiometric assay, and we analysed the association between serum CGRP level and clinicopathological factors. Results:, Serum CGRP levels in the patients with higher clinical stages and histological grade were significantly higher than in those with lower stages and grade, respectively. But the levels did not correlate with the patient's age, liver or renal functions, serum prostate-specific antigen levels. Conclusion:, Serum CGRP levels were significantly elevated in the patients with high grade or high stage untreated prostate cancer patients. Measurement of the serum CGRP may be a useful predictor of staging or grading of prostate cancer in the untreated prostate cancer patients. [source] The prognostic value of p53, Ki-67 and matrix metalloproteinases MMP-2 and MMP-9 in transitional cell carcinoma of the renal pelvis and ureterINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2005SHUICHI KAMIJIMA Aim: To investigate the prognostic and predictive relevance of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 in patients with transitional cell carcinoma (TCC) of the upper urinary tract. Methods: The expression of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 was examined by immunohistochemistry in 69 patients with TCC of the upper urinary tract. Correlation of p53, Ki-67, MMP-2 and MMP-9 over-expression with conventional pathological parameters and patient survival was examined. Results: p53 over-expression was signi,cantly correlated with histological grade (P < 0.05), but not with pathological stage, vascular invasion, lymphatic invasion or lymph node metastasis. Ki-67 over-expression was signi,cantly correlated with stage, grade, lymphatic invasion and vascular invasion (P < 0.05). In survival analyses, Ki-67 over-expression was a signi,cant prognostic factor in the univariate analysis (P < 0.05), but it did not have a signi,cant impact on survival in the multivariate analysis. Ki-67 labeling index was a signi,cant prognostic factor in patients with a low p53 labeling index, but not in patients with a high p53 labeling index. Conclusion: Ki-67 over-expression is of prognostic value in TCC of the upper urinary tract, while p53, MMP-2 and MMP-9 are of limited value. [source] Combined histology and molecular biology for diagnosis of early stage gastric MALT lymphomaJOURNAL OF DIGESTIVE DISEASES, Issue 1 2006Zhi Hui YI OBJECTIVE: To establish a sequential diagnostic procedure of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and provide evidence for selected optimal cases to be treated in the early stage. METHODS: Thirty-one cases of gastric lymphoid hyperplasia (GLH) were selected and multiple investigations including histology, protein level, DNA and chromosome levels, combined with clinical follow-up were performed. Histological grade was according to Isaacson's criteria of GLH; CD20, UCHL-1 (CD45RO), anti-kappa (,), anti-lambda (,) and Ki-67 were used for immunohistochemical staining; semi-nested polymerase chain reaction (PCR) was used to detect IgH gene rearrangement and reverse-transcription PCR (RT-PCR) was used to detect API2-MALT1 fusion of the chromosome translocation t(11;18)(q21;q21). Twenty-nine cases underwent eradication therapy for Helicobacter pylori. Changes in histological grade, endoscopic appearance, expression of Ki-67 and IgH gene rearrangement were compared after eradication treatment. RESULTS: Of the 31 cases of GLH with predominant chronic gastritis and gastric ulcer most were histological grade 2 and 3. Only one case had , light chain restriction and 10 cases had monoclonal IgH gene rearrangement. Expression of Ki-67 and monoclonal IgH gene rearrangement were significantly increased with increased lymphoid hyperplasia (P < 0.05). Two cases had API2-MALT1 fusion. Helicobacter pylori was eradicated in 25 cases and another course of treatment had to be given in 4 cases. All cases were followed up for 1.5,37 months. Of the 27 successful eradication cases, 18 showed complete regression both histologically and endoscopically, 4 had partial regression and 7 were unchanged. CONCLUSIONS: A sequential diagnostic procedure based on histology, expression of Ki-67 combined with clonality of IgH rearrangement and API2-MALT1 fusion helps to diagnosis of early stage gastric MALT lymphoma and choose the best treatment strategy. [source] Common single nucleotide polymorphism of hypoxia-inducible factor-1, and its impact on the clinicopathological features of esophageal squamous cell carcinomaJOURNAL OF DIGESTIVE DISEASES, Issue 4 2005Ting Sheng LING OBJECTIVE: Angiogenesis is one of the most important molecular events in solid tumor development and growth, in which hypoxia-inducible factor (HIF)-1, is a key regulator and plays an important role. Studies have shown that a single nucleotide polymorphism (C1772T) in the HIF-1, gene exerts a large effect on the phenotype of human head and neck squamous cell carcinoma and renal cell carcinoma. But the impact of the C1772T polymorphism on the clinicopathological features of human esophageal squamous cell carcinoma (ESCC) remains unknown, and thus it is the main focus of our study. METHODS: The C1772T genotype of 95 ESCC patients and 104 healthy controls were studied by using the polymerase chain reaction and restriction fragment length polymorphism. Mutations were confirmed by direct DNA sequencing. The impact of C1772T on tumor size, invasive depth, lymph node metastasis, distant metastasis, histological grade and TNM stage was also studied. RESULTS: The genotype frequency observed in the patients and controls was 11.58% versus 10.58%, respectively, for genotype C/T (P > 0.05). Genotype T/T was not found in our study. Larger tumors and a higher rate of lymph node metastasis was found for the C/T group. CONCLUSIONS: Although there is no significant difference of genotype distribution between ESCC patients and healthy controls, genotype C/T is associated with larger tumor and higher rate of lymph node metastasis. [source] Long-term outcome of chronic hepatitis B based on histological grade and stageJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2007Byung Kyu Park Abstract Background and Aim:, This study evaluated the long-term outcome and prognostic factors of chronic hepatitis B, based on histological grade and stage. Methods:, A total of 188 patients with chronic hepatitis B were followed for a mean 119.8 months. Ultrasonography and clinical assessment were performed regularly. In addition, liver biopsy specimens were re-evaluated based on histological grade and stage. Results:, During follow-up, cirrhosis developed in 62 patients, decompensation in 20 patients, and hepatocellular carcinoma (HCC) in 21 patients. The serum alanine aminotransferase (ALT) level at the time of liver biopsy was significantly correlated with the grades of lobular and porto-periportal activity. The development of cirrhosis correlated well with the grade of porto-periportal activity and stage of fibrosis. The probabilities of developing cirrhosis, decompensation and HCC were significantly higher in patients whose ALT levels were persistently elevated without flares or flared-up without normalization than in patients whose ALT levels flared-up then normalized or were normally sustained. By multivariate analysis, age and biochemical profile during follow-up were independent prognostic factors for chronic hepatitis B. Conclusions:, The results demonstrate that histological grade and stage, and biochemical profile during follow-up in patients with chronic hepatitis B are important prognostic factors. Therefore, effective control of hepatitis activity might improve the long-term outcome of chronic hepatitis B patients. [source] Aspartate aminotransferase : alanine aminotransferase ratio in chronic hepatitis C infection: Is it a useful predictor of cirrhosis?JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2000Gordon J-H Park Abstract Background: The clinical usefulness of the ratio of serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) has been explored in several liver disorders. It has been suggested that in patients with chronic hepatitis C virus (HCV) infection an AST : ALT , 1 has 100% specificity and positive predictive value in distinguishing cirrhotic from non-cirrhotic patients. Such statistical certainty attached to a simple biochemical test merits further evaluation. The present study, therefore, assessed the AST : ALT in patients with chronic HCV infection to determine the validity of the ratio in predicting cirrhosis and to correlate the ratio with the histological grade of necroinflammatory activity and fibrosis. Methods: A retrospective analysis of 153 patients with chronic HCV infection was conducted. Serum biochemistry had been obtained within a mean of 4 weeks of liver biopsy. The histology was scored in terms of activity and fibrosis as described by Scheuer and correlated with AST : ALT. Results: In 30 patients with cirrhosis, the mean AST : ALT (0.99 ± 0.06) was higher than in 123 patients without cirrhosis (0.60 ± 0.02; P < 0.001). A ratio , 1 had 95.9% specificity and 73.7% positive predictive value in distinguishing cirrhotic from non-cirrhotic patients, with a 46.7% sensitivity and 88.1% negative predictive value. The ratio also parallelled the Scheuer score with respect to fibrosis but not with respect to inflammation. Conclusion: Although relatively insensitive, an AST : ALT , 1 is highly specific but not diagnostic for the presence of cirrhosis in patients with chronic HCV infection. The ratio reflects the grade of fibrosis in these patients. [source] Prognostic factors in endometrial carcinomaJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2008Peter Uhar Abstract Endometrial carcinoma is the most common malignancy of the female genital tract in industrialized countries, and occurs predominantly after the menopause. Although most endometrial carcinomas are detected at low stage, there is still a significant mortality from the disease. In postmenopausal women, prolonged life expectancy, changes in reproductive behavior and prevalence of overweight and obesity, as well as hormone replacement therapy use, may partially account for the observed increases of incidence rates in some countries. In order to improve treatment and follow-up of endometrial carcinoma patients, the importance of various prognostic factors has been extensively studied. The identification of high-risk groups would make it possible to avoid unnecessary adjuvant treatment among patients with a good prognosis. Over the past few decades, several studies have demonstrated the prognostic importance of different parameters including lymph node status, histological type of carcinoma (serous carcinoma and clear cell carcinomas are poor prognostic types), histological grade, stage of disease, depth of myometrial invasion, lymphovascular space involvement and cervical involvement. Other factors currently being investigated are estrogen and progesterone receptor status, p53 status, flow cytometric analysis for ploidy and S-phase fraction, and oncogenes such as HER-2/neu (c-erbB-2). [source] Serum carbohydrate antigen elevations in endometrial adenocarcinomas: Characterization of DU-PAN-2 expression as a tumor markerJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2004Masanori Yasuda Abstract Aim:, To characterize serum elevations of carbohydrate antigens; DU-PAN-2, CA19-9, sialyl Lewisx and CA125 in endometrial adenocarcinomas (EMACs), particularly focusing on the clarification of DU-PAN-2 expression profiles. Methods:, Sixty-four resected EMACs of endometrioid type were used. The preoperative serum values of four markers were measured and comparatively analyzed regarding the relationship between histological grade and clinicopathological stage. Results:, The overall ratios of positive cases were 26.2% for DU-PAN-2, 25.0% for CA19-9, 13.6% for sialyl Lewisx, and 35.5% for CA125. DU-PAN-2 decreased as the grading went up (G1: 410.3 ± 243.8 to G3: 246.7 ± 90.0 U/mL), however, the reverse was true with CA19-9 (G1: 123.9 ± 147.4 to G3: 320.0 ± 180.0 U/mL). Sialyl Lewisx showed a strong tendency towards high elevation in G1 (346.3 ± 102.6 U/mL), compared to G3 (<2.5 U/mL). CA125 increased markedly as the grading went up (G1: 43.5 ± 6.3 to G3: 578.0 ± 10.0 U/mL). During staging-up from I + II to III + IV, the positive ratios inclined in all four markers as follows: DU-PAN-2, 18.4,53.3%; CA19-9, 20.4,40.0%; sialyl Lewisx, 11.4,22.2%; CA125, 31.8,44.4%. Serum elevations and positive ratios were correlated for DU-PAN-2, CA19-9 and CA125, while the reverse relationship was found for sialyl Lewisx. Conclusion:, It is suggested that DU-PAN-2 tends to be produced more in well-differentiated components of EMACs than in poorly differentiated ones. Since approximately half the cases with EMAC were serologically positive for DU-PAN-2 in stage III + IV, the marker is believed to be of much use for monitoring the cases with an extrauterine extent. [source] Prognostic significance of tumor shape and stromal chronic inflammatory infiltration in squamous cell carcinomas of the oral tongueJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2010Ioulia Chatzistamou J Oral Pathol Med (2010) 39: 667,671 Background:, Squamous cell carcinoma (SCC) of the oral tongue is well known to be an aggressive disease with early metastatic spread in early stage tumors. It is also established that locoregional recurrences are the main causes of treatment failure. Thus, the identification of histopathological factors possessing a predictive value remains important for the management of the disease. The aim of the present study was to define histopathological parameters of the tumor and to compare with the follow-up and status in primary SCCs of the mobile tongue. Methods:, Histopathological parameters such as mitotic index, the presence of vascular emboli or perineural invasion, the thickness of the tumor, the histological grade, the tumor shape as well as chronic stromal inflammatory infiltration were assessed in 52 patients with SCC of the mobile tongue and compared with the follow-up and status in patients treated initially by surgery. Results:, Tumor shape was significantly associated with the presence of perineural invasion. Well-defined shaped tumors displayed almost half the incidence of perineural invasion when compared with ill-defined shaped tumors. In addition, the high density of the chronic inflammatory infiltration of the stroma exhibited significant correlation with the survival of the patients. Finally, the intense chronic inflammatory infiltration of the stroma was associated with well-defined shaped tumors. Conclusion:, Tumor shape and stromal chronic inflammatory infiltration should be considered in the planning of the management of patients with SCC of the mobile tongue. [source] Comparative study of HPV prevalence in Japanese and North-east Chinese oral carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 7 2003Xiaofei Tang Abstract Background:, Human papillomavirus (HPV) plays a role in the development of oral carcinoma. However, the reported prevalence of HPV in oral carcinoma has varied widely. Methods:, The prevalence of HPV 16, 18 and 33 was investigated in Japanese and North-east Chinese oral squamous cell carcinomas (OSCCs) with polymerase chain reaction (PCR). The expression of p53 protein was examined immunohistochemically. Results:, HPV 16 and 18 were detected in 7 (23.3%) and 10 (33.3%) of 30 Japanese and 11 (36.7%) and 5 (16.7%) of 30 Chinese samples, respectively. HPV 16 and 18 coinfection was detected in 3/30 Japanese and 2/30 Chinese samples. HPV 33 was not detected. There was no significant correlation between HPV 16 and 18 and the sites, gender, age and histological grade. The prevalence of both HPV 16 and 18 was similar and higher in the Japanese and North-east Chinese samples (46.7% each). HPV 16 or/and 18 infection or/and p53 overexpression were in 22 (73.3%) of 30 Japanese samples and 24 (80.0%) of 30 North-east Chinese samples, respectively. Conclusions:, HPV 16/18 infection or/and p53 overexpression may play an important role in developing some OSCCs. and the presence of HPV sequences and mutant p53 are not necessarily mutually exclusive. [source] The correlation between alteration of p16 gene and clinical status in oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2001Chung-Hung Tsai Abstract: The purpose of the study was to evaluate the presence of alteration of the tumor suppressor gene p16 and to correlate these changes with the clinical status of the patients in oral squamous cell carcinoma. Forty-eight oral squamous cell carcinomas were included in the analyses. Deletion analysis was performed by the polymerase chain reaction (PCR). Mutation analysis was restricted to exon 1 and exon 2 of the p16 gene, previously shown to have a high incidence of mutations. The sequences containing exon 1 and exon 2 were amplified by PCR and screened with a single-strand conformation polymorphism (SSCP) technique. Samples showing band shifts in SSCP were sequenced by PCR direct sequencing. Western blots were used to detect the protein expression of the p16 gene, and the results were evaluated with regard to their biological relevance in correlation with clinicopathological factors. Seven (14.6%) deletions were found; 5 (10.4%) mutations were discovered and located in different codons; 26 (54%) specimens had no p16 protein expression; in 11 specimens with p16 deletion or mutation, p16 protein could not be detected. One mutation was non-sense. The p16 gene alterations showed no relationship with location and clinical stage of cancer; however, a close relationship between p16 alterations and cancer metastasis to neck lymph node was found. The alteration rate gradually elevated from well to poorly differentiated grades. We perceive two results. First, the alterations of the p16 gene are common in oral squamous cell carcinoma. Second, the alterations of the p16 gene may attribute to the metastatic behavior or histological grade of cancer cells. [source] Multidetector row computed tomography for diagnosing intraductal extension of breast carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 1 2005Takeo Fujita Abstract Objectives Several reports supported the association of higher ipsilateral breast tumor recurrence rates with positive or intermediate margins compared with negative pathologic margins. Precise evaluation of intraductal component and adequate surgical margin are important factors affecting the tumor recurrence after breast conserving surgery. Numerous studies have reported the utility of magnetic resonance imaging for diagnosing developing intraductal extension of breast cancer, but few have investigated multidetector-row computed tomography (MD-CT). The present study evaluated the clinical utility of MD-CT for detecting intraductal extension of breast carcinoma, and analyzed clinical parameters affecting the detection of intraductal extension under MD-CT. Methods Subjects comprised 44 patients grouped into three categories according to degree of intraductal extension of the main tumor under MD-CT (Intraductal spread grade 1,3: IDS 1,3). Tumors were also categorized histopathologically (p-IDS 0,3), and CT-pathological correlations were examined retrospectively. Clinical parameters were evaluated to determine the affect on detection of intraductal components. Results MD-CT detected 44 breast lesions (100%). Sensitivity for detection of intraductal component was 81.2%, specificity was 67.8%, and accuracy was 72.7%. Regarding extent of intraductal components, significant correlations were found between histopathological and MD-CT findings. A strong correlation was found in postmenopausal women between T2 tumor and high histological grade. Conclusions MD-CT findings of intraductal extension from breast carcinoma correlate with histological degree of intraductal extension, and MD-CT may be useful for preoperative assessment of breast-conserving surgery, particularly for postmenopausal women with histological high nuclear grade and T2 tumor. J. Surg. Oncol. 2005;91:10,16. © 2005 Wiley-Liss, Inc. [source] Assessment of hepatic steatosis: comparison of quantitative and semiquantitative methods in 108 liver biopsiesLIVER INTERNATIONAL, Issue 4 2009Bruno Turlin Abstract Background: There is growing interest in the role of hepatic steatosis in liver injury. The current standard for steatosis assessment is histological grading, although there is variability in the scoring systems used. Aims: The aim of this study was to compare steatosis assessment by image analysis and histological grading. Methods: Three methods were used to measure steatosis: histological grading (from 0 to 4); estimation of the percentage of hepatocytes (to nearest 5%) with steatosis; and computer-assisted image analysis. Image analysis was performed on multiple fields for each biopsy with image pro plus 4.5, with steatotic droplets identified on the basis of shape, colour and size. Computer-selected objects were reviewed to ensure that these were steatotic droplets. The predictive accuracy of the three techniques was assessed using measures of obesity and insulin resistance (homeostasis model assessment) as the outcome variables. Results: There was a strong correlation between the results of image analysis and histological grade (rs=0.89, P<0.01), and estimated per cent steatosis (rs=0.93, P<0.01). The variability in the area of steatosis calculated by image analysis in different fields of a biopsy correlated with the total steatosis area (rs=0.93, P<0.01). Conclusions: Image analysis did not offer any additional predictive value when the association between degree of obesity or insulin resistance was correlated with the different methods of assessing steatosis. Image analysis allows measurement of area of steatosis in liver biopsy material and generates a continuous variable that facilitates statistical analysis. These aspects may prove beneficial in research settings. [source] Prognostic implications of ezrin expression in human hepatocellular carcinomaMOLECULAR CARCINOGENESIS, Issue 9 2010Yun Kyung Kang Abstract Ezrin is known to regulate cellular survival, adhesion, migration, and invasion and has been identified as one of the key components of tumor progression and metastasis. The authors investigated ezrin expression in human hepatocellular carcinoma (HCC) and sought to determine its relation with clinicopathologic parameters, patients' outcome, and interacting molecular markers. Ezrin expression was assessed by immunohistochemical staining in 100 surgically resected HCCs using the tissue microarray method. A total of 28 HCCs showed high ezrin immunoreactivity, mainly in cytoplasm. Ezrin expression exhibited a positive correlation with c-Met expression (P,=,0.001), but showed no correlation with the expression of CD44s or E-cadherin. HCCs expressing high level of ezrin were significantly associated with advanced TNM stage, poor Edmondson's histological grade, macroscopic portal vein invasion, tumor recurrence, and extrahepatic recurrence (P,<,0.05). Univariate analysis showed that HCCs with high ezrin immunoreactivity were strongly associated with unfavorable overall and disease-free survivals than HCCs with low or negative for ezrin immunoreactivity (P,=,0.0001 and 0.0011, respectively). Furthermore, multivariate analysis demonstrated that a high level of ezrin expression was independently associated with poor overall survival (hazard ratio, 1.905; P,=,0.011). The results suggest that ezrin expression could be a potential predictive marker of progression, metastasis, and prognosis in HCC. © 2010 Wiley-Liss, Inc. [source] Identification of MRI and 1H MRSI parameters that may predict survival for patients with malignant gliomasNMR IN BIOMEDICINE, Issue 1 2004Xiaojuan Li Abstract Although MR imaging (MRI) and MR spectroscopic imaging (MRSI) have been applied in the diagnosis and treatment planning for brain tumors, their prognostic significance has not yet been determined. The goal of this study was to identify pre-treatment MRI and MRSI parameters for patients with malignant glioma that may be useful in predicting survival. Two populations of patients with newly-diagnosed malignant glioma were examined with MRI and three-dimensional proton (1H) MRSI. Thirty-nine patients (22 grade 3 and 17 glioblastoma multiforme, GBM) were studied prior to surgery, and 33 GBM patients were studied after surgery but prior to treatment with radiation and chemotherapy. Signal intensities of choline (Cho), creatine (Cr), N -acetyl aspartate (NAA), and lactate/lipid (LL) were estimated from the spectra. Recursive partitioning methods were applied to parameters that included age, histological grade, MRI and MRSI variables to generate survival trees. Patients were grouped into high and low risk categories and the corresponding Kaplan,Meier curves were plotted for comparison between groups. The parameters that were selected by recursive partitioning as being predictive of poor outcome were older age, larger contrast enhancement, higher Cho-to-Cr, higher Cho-to-NAA, higher LL and lower Cr-to-NAA abnormalities. The survival functions were significantly different between the sub-groups of patients obtained from the survival tree for both pre-surgery and post-surgery data. The results of this study suggest that pre-treatment MRI and three-dimensional 1H-MRSI provide information that predicts outcome for patients with malignant gliomas and have drawn attention to variables that should be examined prospectively in future studies using these techniques. Copyright © 2004 John Wiley & Sons, Ltd. [source] Ki-67 expression in non-tumour epithelium adjacent to oral cancer as risk marker for multiple oral tumoursORAL DISEASES, Issue 1 2010MA González-Moles Objective:, The aim of this study was to determine whether the differential assessment of epithelial proliferation is useful to diagnose premalignant fields and assess the risk of multiple tumours. Material and methods:, We analysed 83 oral carcinomas with associated non-tumour epithelium classified as distant or close according to its distance (> or <1 cm) from the invasion point, and as squamous hyperplasia, mild, moderate, severe dysplasia or carcinoma in situ. Twenty-five healthy oral mucosa samples were used as controls. An immunohistochemical technique was applied using Mib-1. Ki-67 in premalignant epithelium was assessed in basal layer, parabasal layer, medium and upper third. Results:, Parabasal expression was significantly higher or showed a tendency to be higher in close and distant epithelia with any histological grade than in the controls. Parabasal Ki-67 significantly differed between distant epithelia associated with multiple vs single tumours (P < 0.001) and between distant epithelia associated with multiple tumours vs controls (P < 0.001). This difference was not observed between distant epithelia associated with single tumours and controls (P = 0.175). The cut-off point that differentiated epithelia associated with multiple tumours was >50% of Ki-67 + parabasal cells in distant epithelia, which yielded 0.88 sensitivity and 0.79 specificity. Conclusions:, The concept of a precancerous field may be linked to an increase in the proliferative activity of parabasal cells. [source] |