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Precancerous Lesions (precancerou + lesion)
Kinds of Precancerous Lesions Selected AbstractsExpression profiling in multistage hepatocarcinogenesis: Identification of HSP70 as a molecular marker of early hepatocellular carcinomaHEPATOLOGY, Issue 1 2003Makoto Chuma Hepatocellular carcinoma (HCC) associated with chronic liver disease evolves from precancerous lesions and early HCC to a progressed form. Nodule-in-nodule,type HCC (progressed HCC within early HCC) represents the transition from early to progressed HCC and, therefore, is useful in molecular genetic analysis of HCC progression during multistage carcinogenesis. We compared expression profiles among 7 early components and 7 progressed components of nodule-in-nodule,type HCCs and their corresponding noncancerous liver tissues with oligonucleotide array. Of the approximately 12,600 genes that were analyzed, a set of 95 genes provided a molecular signature that distinguished between early HCC components and their noncancerous liver tissues, and a set of 92 genes distinguished between progressed and early HCC components. Of these genes, the most abundantly up-regulated gene in early HCC components (P < .001) was heat-shock protein 70 (HSP70). Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed this finding. Further immunohistochemical examination of HSP70 revealed its significant overexpression in early HCC compared with precancerous lesions (P < .001) and in progressed HCC compared with early HCC (P < .001). In conclusion, molecular signatures were clearly different in noncancerous liver tissue as compared with the early and progressed components of nodule-in-nodule,type HCC. Moreover, HSP70 could be a sensitive marker for the differential diagnosis of early HCC from precancerous lesion or noncancerous liver, a difficult distinction for pathologists due to very well differentiated histology with little atypia in early HCC. [source] Low-grade dysplasia component in early invasive squamous cell carcinoma of the esophagusJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2010Yuichi Shimizu Abstract Background and Aims:, It has not been determined whether low-grade squamous dysplasia (LGD) of the esophagus is a precancerous lesion or not. If LGD progresses to squamous cell carcinoma, early carcinoma lesions that have such a natural history might contain a remaining LGD component. Methods:, The lesions in the 68 patients with early invasive squamous cell carcinoma who underwent endoscopic mucosal resection were examined for the presence of an LGD component. If LGD components were observed, the degrees of architectural and cytological abnormalities of LGD components and those of tumor invasive fronts in the same lesions were studied. The degrees of abnormalities of 28 small LGD lesions were also studied. Results:, Histological examination of resected specimens confirmed LGD components in 43% of the squamous cell carcinoma lesions. The lesions of lamina propria mucosae (m2) cancer contained a significantly broader area of LGD component than did the lesions of muscularis mucosae (m3) and submucosal layer (sm) cancer (P = 0.037). Mean score for the degrees of cytological abnormalities of LGD component was similar to that of tumor invasive front (P = 0.457) and significantly higher than that of small LGD lesions (P < 0.001). Conclusion:, Our results indicate the possibility that the lesion was formed by a combination of small lesions that arose as a multicentric occurrence of squamous cell carcinoma and dysplasia. Our results also suggest that an LGD component would transform to carcinoma along with tumor progression. However, the concept of ,basal cell layer type carcinoma in situ' may be suitable for squamous cell lesions with a high degree of cytological abnormalities confined to the lower half of the epithelium. [source] Genetic polymorphism of cytochrome P4501A1 and susceptibility to oral squamous cell carcinoma and oral precancer lesions associated with smoking/betel useJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2002Shou-Yen Kao Abstract Background:,, The importance of the CYP1A1 polymorphisms at exon 7 (Ile/Val) and 3,-untranslated region (3,-UTR) has been controversial in oral squamous cell carcinoma (OSCC) or head and neck SCC (HNSCC) denoting the value of exploring the correlation between these polymorphisms and risk of betel/smoking associated OSCC. It is also important to evaluate the association between CYP1A1 polymorphisms and susceptibility of oral precancerous lesion (OPL) to confirm the findings in OSCC cases. Methods:,, We examined polymorphic prevalence of CYP1A1 at exon 7 (Ile/Val) and 3,-UTR in 106 cases with OSCC, 60 cases with OPL, and 146 controls. DNA isolated from surgical specimens and whole blood was used for PCR-based genotyping. Results:,, The prevalence of the CYP1A1 A/G genotype (Ile/Val) and G/G genotype (Val/Val) in exon 7 of cases with OSCC (79.2 and 7.6%) and OPL (68.3 and 10%) were significantly higher than in controls (53.4 and 1.4%) (P < 0.0001). The novelty of the present study is that we identified the onset age of OSCC in CYP1A1 A/G genotype to be significantly younger than that in A/A genotype (P < 0.01). No significant difference was seen between cases and controls regarding the polymorphisms at 3,-UTR. Conclusion:,, The findings indicate that the individuals with the CYP1A1 exon 7 containing G allele were at increased risk for OSCC and OPL. [source] Dysplastic nodules frequently develop into hepatocellular carcinoma in patients with chronic viral hepatitis and cirrhosisCANCER, Issue 3 2006Masahiro Kobayashi M.D. Abstract BACKGROUND Advances in imaging technology have enhanced the detection of small nodular lesions during the course of chronic liver disease. METHODS Between 1995 and 2002, the authors examined 154 consecutive patients with small hepatic nodules without hepatocellular carcinoma (HCC) over a median duration of 2.8 years. The median size of these nodules was 14 mm (range, 7,40 mm). The initial histopathologic diagnosis included high-grade dysplastic nodule (HGDN) (n = 13), low-grade dysplastic nodule (LGDN) (n = 42), and regenerative nodule (RN) (n = 99). RESULTS A total of 29 (18.8%) nodules developed into HCC during the observation period. Cumulative HCC development rates at the first, third, and fifth year were 46.2%, 61.5%, and 80.8% for HGDN; 2.6%, 30.2%, and 36.6% for LGDN; and 3.3%, 9.7%, and 12.4% for RN, respectively. The rate of HCC development was significantly higher in the HGDN group than for other types (P < 0.001). Multivariate analysis disclosed that histopathologic diagnosis (P < 0.001) and findings on computed tomographic arterial portography (CT-AP) (P = 0.004) were significantly associated with future HCC development. The hazard ratios of HGDN and LGDN were 16.8 (95% confidence interval [CI], 6.19,45.6) and 2.96 (95% CI, 1.20,7.31), respectively. A decrease in portal blood flow also showed a significantly high hazard ratio of 3.04 (95% CI, 1.42,6.50). Approximate annual development rate to HCC was 20% in patients with HGDN and 10% in LGDN. CONCLUSION HGDN should be considered a precancerous lesion when it appears during follow-up of chronic viral hepatitis or cirrhosis. Reduced portal blood flow in the nodule on computed tomography-AP is also an important predictor for development of hepatocellular carcinoma. Cancer 2006. © 2005 American Cancer Society. [source] Use of topical immunomodulators in organ transplant recipientsDERMATOLOGIC THERAPY, Issue 1 2005Bradley T. Kovach ABSTRACT:, Solid organ transplant recipients are a growing population at increased risk for the development of cutaneous premalignant and malignant lesions, resulting in significant morbidity and mortality. Topical immunomodulators, in particular imiquimod, have shown efficacy in the management of multiple malignant, precancerous, and viral conditions. The ability to locally induce an immune response, presumably against tumor and viral antigens, and induce apoptosis makes topical immunomodulators a promising therapeutic option in organ transplant recipients. Although limited, data have begun to accumulate on the use of imiquimod in transplant patients for the management of superficial, nodular, and infiltrative basal cell carcinomas; in situ and invasive squamous cell carcinomas; condyloma acuminata; and common warts. As more experience is gathered, the role of imiquimod and other topical immunomodulators in the care of OTRs will be clarified. The authors reviewed the existing data on the use of topical imiquimod in OTRs with mention of its presumed mechanisms of action and other immunomodulators with potential efficacy against cancerous and precancerous lesions. [source] Helicobacter Pylori and Precancerous Gastric LesionsDIGESTIVE ENDOSCOPY, Issue 3 2000Pham Quang Cu Background: To determine the relationship between Helicobacter pylori (H. pylori) infection and the precancerous gastric lesions: atrophic gastritis (AG) and intestinal metaplasia (IM) and dysplasia. Methods: A total of 347 dyspeptic patients, including 141 H. pylori -positive patients and 206 H. pylori -negative patients, were studied alongside age- and sex-matched controls. The patients underwent gastroscopy and endoscopic biopsy for detection of H. pylori, and histological examinations. Helicobacter pylori was detected by a urease test (CLO; Delta West; Bentley, Australia), by histology (H&E stain, Giemsa) and by serology (BioSig; BioMeditech, NJ, USA). Atrophic gastritis, IM and dysplasia were detected by histological examination (Giemsa, H&E stain). Results: There is a higher rate of atrophic gastritis in H. pylori -positive than in H. pylori -negative patients (46 vs 13.5%, odds ratio (OR) = 5.4; P < 0.01). Gastritis in H. pylori -positive patients also has a higher rate of activity than in H. pylori -negative patients. The rate of IM is higher in H. pylori -positive patients than in H. pylori -negative patients (35 vs 11%; OR = 4.3; P < 0.01). Metaplasia is more often diffuse in H. pylori -positive than in H. pylori -negative patients. Dysplasia is more common in H. pylori -positive than in H. pylori -negative patients (12 and 3.8%; OR = 3.3; P < 0.01). Conclusions: This study supports the suggestion of a relationship between H. pylori infection and precancerous gastric lesions. Wherever H. pylori is present, the precancerous lesions are more common and more severe. [source] Clinical value of optical coherence tomography in laryngologyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2008Marcel Kraft MD Abstract Background. Optical coherence tomography (OCT) is a new, noninvasive imaging technology for the evaluation of superficial lesions. The objective of this study is to evaluate microlaryngoscopy in combination with OCT compared with microlaryngoscopy alone (ie, without OCT) in supplying a specific diagnosis, predicting invasive tumor growth and epithelial dysplasia in the larynx. Methods. This was a prospective study including 217 laryngeal lesions in a total of 193 patients undergoing surgery. Intraoperative suspicion diagnosis gained by microlaryngoscopy with and without OCT was compared with conventional histopathology after excisional biopsy. Results. Microlaryngoscopy with OCT supplied a specific diagnosis in 89% of cases, but in only 80% of cases with microlaryngoscopy alone. In particular, our results in malignant and benign pathologies were correct in 93% each, and the exact grade of dysplasia could be predicted in 71% of precancerous lesions. Microlaryngoscopy with OCT presented a higher sensitivity than microlaryngoscopy alone in predicting invasive tumor growth (93% vs 87%) and epithelial dysplasia (78% vs 66%), but the specificity and accuracy were comparable in both methods. Conclusions. OCT is a simple, rapid, and reliable aid in the diagnostic investigation and intraoperative monitoring of laryngeal disease. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source] Inducible nitric oxide synthase expression in laryngeal neoplasia: Correlation with angiogenesisHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2002Alessandro Franchi MD Abstract Background The nitric oxide (NO) pathway plays a relevant role in angiogenesis and tumor progression in squamous cell carcinoma (SCC) of the head and neck. The aim of this study was to assess whether the NO pathway may be correlated with angiogenesis in the transition from laryngeal dysplasia to invasive carcinoma. Methods We investigated the expression of the inducible NO synthase (iNOS) in 26 laryngeal precancerous lesions and 35 squamous cell carcinomas with respect to microvessel density. In addition, we determined iNOS activity and cGMP levels in specimens from SCCs. Results There was a significant increase of iNOS levels detected immunohistochemically passing from hyperplastic/mild dysplastic to moderate/severe dysplastic lesions to SCC (p = .04). Accordingly, Northern and Western analyses demonstrated higher iNOS mRNA and protein levels in SCCs than dysplastic mucosa. iNOS expression was significantly correlated with microvessel counts both in the group of preneoplastic lesions (p = .02) and in the group of SCCs (p = .01). In addition, iNOS activity was correlated with iNOS immunohistochemical expression (p = .1) and was significantly associated with increased vascularization (p = .03) in SCCs. Similarly, iNOS expression was significantly correlated with cGMP levels in SCC (p = .02) and increased tumor vascularization correlated with higher cGMP levels (rs = .4; p = .01). Conclusions Our data indicate that the NO pathway may play a relevant role in the angiogenesis associated with the progression from laryngeal dysplasia to laryngeal SCC. © 2002 John Wiley & Sons, Inc. Head Neck 24: 16,23, 2002. [source] Expression profiling in multistage hepatocarcinogenesis: Identification of HSP70 as a molecular marker of early hepatocellular carcinomaHEPATOLOGY, Issue 1 2003Makoto Chuma Hepatocellular carcinoma (HCC) associated with chronic liver disease evolves from precancerous lesions and early HCC to a progressed form. Nodule-in-nodule,type HCC (progressed HCC within early HCC) represents the transition from early to progressed HCC and, therefore, is useful in molecular genetic analysis of HCC progression during multistage carcinogenesis. We compared expression profiles among 7 early components and 7 progressed components of nodule-in-nodule,type HCCs and their corresponding noncancerous liver tissues with oligonucleotide array. Of the approximately 12,600 genes that were analyzed, a set of 95 genes provided a molecular signature that distinguished between early HCC components and their noncancerous liver tissues, and a set of 92 genes distinguished between progressed and early HCC components. Of these genes, the most abundantly up-regulated gene in early HCC components (P < .001) was heat-shock protein 70 (HSP70). Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed this finding. Further immunohistochemical examination of HSP70 revealed its significant overexpression in early HCC compared with precancerous lesions (P < .001) and in progressed HCC compared with early HCC (P < .001). In conclusion, molecular signatures were clearly different in noncancerous liver tissue as compared with the early and progressed components of nodule-in-nodule,type HCC. Moreover, HSP70 could be a sensitive marker for the differential diagnosis of early HCC from precancerous lesion or noncancerous liver, a difficult distinction for pathologists due to very well differentiated histology with little atypia in early HCC. [source] Enhanced expression of MMP-7 and MMP-13 in inflammatory bowel disease: A precancerous potential?INFLAMMATORY BOWEL DISEASES, Issue 11 2006Dr. Timo Rath PhD Abstract Matrix metalloproteinases (MMPs) are responsible for the turnover and degradation of extracellular matrix. They play a crucial role in the growth and migration of colorectal carcinoma cells. Colorectal carcinomas are characterized by enhanced expression of MMP-2, MMP-9, MMP-7, and MMP-13. The aim of this study was to determine the expression levels of MMP-2, MMP-9, MMP-7, MMP-13, and MMP-14 and their specific inhibitor TIMP-1 in inflammatory bowel diseases and precancerous lesions of the colon, i.e., Crohn's disease and ulcerative colitis, and in adenomatous polyps (APs) for comparison. Biopsy samples of pathological and healthy tissue were obtained from 40 patients with inflammatory bowel disease (ulcerative colitis, n = 17; Crohn's disease, n = 23) and from 19 patients with APs. mRNA was measured by quantitative real-time polymerase chain reaction to study MMP and TIMP-1 gene expression in both pathological and normal mucosal specimens. For MMP-2, MMP-9, and TIMP-1, protein expression also was quantified with sandwich enzyme-linked immunosorbent assay. In biopsy specimens of Crohn's disease and ulcerative colitis, significantly increased levels of MMP-2, MMP-7, and MMP-13 mRNA were found. MMP-2 and MMP-9 showed enhanced secretion on the protein level. AP revealed an increased transcription of MMP-7 and MMP-13 genes. MMP-14 mRNA was decreased in APs. MMPs, especially MMP-7 and MMP-13, which are expressed primarily on the tumor cell surface, are elevated in inflammatory bowel disease, which may have more chance to evolve into malignancy than normal tissue. In APs, increased expression of MMP-7 and MMP-13 may serve as an early indicator for colorectal carcinogenesis. [source] Host,bacterial interaction in the development of gastric precancerous lesions in a high risk population for gastric cancer in Venezuela,INTERNATIONAL JOURNAL OF CANCER, Issue 7 2006Ikuko Kato Abstract Helicobacter pylori (HP) infection affects over 50% of the world's population. The prevalence is over 90% in populations at high risk for gastric cancer, but clinical outcomes of the infection are highly variable and thus host genetic factors have been suggested to play a role in its outcomes in addition to bacterial factors. In this study, we examined the effects of common functional genetic polymorphisms of several proinflammatory cytokines known to be overexpressed in HP-infected gastric mucosa on the risk of various stages of gastric premalignant lesions. The odds ratios (ORs) and 95% confidence intervals (CI) for atrophic gastritis, intestinal metaplasia and dysplasia were estimated by multinominal logistic regression analysis among 2,033 Venezuelan subjects. There was a significant effect of IL8 -251A allele on the prevalence of dysplasia (p = 0.021). The OR associated with the A-allele was 1.34 (95% CI: 0.82,2.18) for heterozygotes and 2.00 (95% CI: 1.13,3.56) for homozygotes, compared with the TT genotype. Furthermore, there was a statistically significant interaction between the number of A-alleles and HP cag A genotype (p = 0.009), suggesting that the A-allele increased the risk of dysplasia only when cag A was present. The OR for the AA compared with TT genotype was 3.22 (95% CI: 1.60,6.52) in this group. There were no associations with other proinflammatory cytokines studied, i.e., IL1,, IL6, monocyte chemoattractant protein 1 (MCP1) and TNF,, or with other stages of premalignant lesions. The present study provides important evidence suggesting host,bacterial interactions in the development of gastric precancerous lesions. © 2006 Wiley-Liss, Inc. [source] Stromelysin-3 expression is an early event in human oral tumorigenesisINTERNATIONAL JOURNAL OF CANCER, Issue 2 2003Shilpi Soni Abstract Stromelysin-3 (ST3/MMP11) is associated with human tumour progression. To determine the clinical significance of ST3 in oral tumorigenesis, its expression was analysed in different stages of tobacco-associated oral cancer. Immunohistochemical analysis of ST3 expression in 79 oral precancerous lesions, 177 SCCs and 35 histologically normal oral tissues was carried out and corroborated by immunoblotting and RT-PCR. ST3/MMP11 protein expression was observed in 45/79 (57%) precancerous lesions [28/48 (58%) with hyperplasia and 17/31 (55%) with dysplasia] and in 123/177 (70%) oral SCCs. In precancerous lesions, ST3 expression was higher compared to normal oral tissues (p = 0.000) and associated with MVD (p = 0.05), a marker for angiogenesis. ST3 was also expressed in cells cultured from precancerous and cancerous lesions that had undergone epithelial-to-mesenchymal transition. In oral cancer patients, ST3 positivity was associated with lymph node involvement (p = 0.025) and increased intratumoral MVD (p = 0.009). Ninety-eight oral SCC patients were followed up for a period of 94 months (median 22.5 months). Kaplan-Meier survival analysis showed that ST3 expression was not a significant prognostic indicator. ST3 expression in oral hyperplastic and dysplastic lesions suggests its association with progression of phenotypic alterations acquired early during the malignant transformation pathway of oral epithelium and implicates it not only in angiogenesis and invasion but also in tumorigenesis. Thus, ST3 may serve as a potential target for developing molecular therapeutics for early intervention in oral tumorigenesis. © 2003 Wiley-Liss, Inc. [source] Treatment of Helicobacter pylori and prevention of gastric cancerJOURNAL OF DIGESTIVE DISEASES, Issue 1 2008Ting Kin CHEUNG Gastric cancer is the second commonest fatal malignancy in the world with a high incidence in China. Helicobacter pylori infection is an important factor in the pathogenesis of gastric cancer. Epidemiological studies have shown a strong causal relationship between H. pylori infection and gastric cancer. Animal studies also show that eradication of H. pylori infection, especially at the early stage, is effective in preventing H. pylori -related gastric carcinogenesis. H. pylori eradication leads to regression and prevents the progression of gastric precancerous lesions, but only in a minority of cases. H. pylori eradication appears to be the most promising approach in gastric cancer prevention. The current available data in human studies showed that H. pylori eradication can reduce the risk of developing gastric cancer and this strategy is more useful in patients without atrophic gastritis or intestinal metaplasia. A longer follow-up and additional studies are needed for better understanding this issue. [source] Factors affecting the serum gastrin 17 level: an evidence-based analysis of 3906 serum samples among ChineseJOURNAL OF DIGESTIVE DISEASES, Issue 2 2007Zhong ZHANG OBJECTIVE: To investigate the influence of gender, age, site of lesion, disease type and Helicobacter pylori (H. pylori) infection on the human serum gastrin-17 level and to study the diagnostic value of serum gastrin-17 in gastric precancerous lesions and gastric cancer. METHODS: Serum gastrin-17 and serum H. pylori IgG antibody were detected by the ELISA method. The different gastric disease groups were confirmed by endoscopy and histopathology. RESULTS: Among the 3906 serum samples according to the gender, age, site of lesion and the data of different gastric disease groups, the serum gastrin-17 level was markedly higher in people ,60 years old than that in younger age groups. The serum gastrin-17 level increased progressively in the following order: healthy control group, nonatrophic gastritis group, gastric ulcer group, and the serum gastrin-17 level was higher in the atrophic gastritis with dysplasia group than that without it, the lowest level being in the gastric cancer group. Among the 2946 serum samples matched with the site of the lesion, the serum gastrin-17 level was higher in those with antral diseases than in those with gastric corpus diseases. Among the 3805 serum samples matched with the H. pylori infection data, the serum gastrin-17 level was higher in the H. pylori -positive group than in the H. pylori -negative group. CONCLUSIONS: In people over 60 years of age, the serum gastrin-17 level tends to increase. In subjects with precancerous gastric lesions, it may increase significantly with the progression of gastric disease, and ultimately decrease in gastric cancer. Serum gastrin-17 is a good biomarker to differentiate benign from malignant gastric diseases. The site of the gastric lesions is an important factor affecting the serum gastrin-17 level, whereas H. pylori infection is usually associated with its increment. [source] Etiology and prevention of gastric cancer: a population study in a high risk area of ChinaJOURNAL OF DIGESTIVE DISEASES, Issue 4 2005Wei Cheng YOU A series of studies has been carried out in Linqu County, Shandong Province, China, a high-risk area for gastric cancer, to investigate the risk factors associated with gastric cancer, precancerous lesions and the prevention of gastric cancer. Our studies showed that sour pancakes (a popular local food), salted foods, cigarette smoking, and family history of gastric cancer were risk factors, whereas fresh vegetables, and intake of vitamin C and calcium were inversely associated with the risk of gastric cancer. The prevalence of chronic atrophic gastritis was approximately 20% in an adult population in Linqu County, intestinal metaplasia was approximately 50%, and dysplasia was approximately 20%. A follow-up study showed that the relative risk of developing gastric cancer increased with the severity of gastric lesions, and was associated with dietary factors, cigarette smoking and H. pylori infection in this population. The findings strongly support the idea that gastric cancer is primarily determined by environmental factors and develops in a multistep progression of precancerous lesions. [source] Deregulation of E-cadherin,catenin complex in precancerous lesions of gastric adenocarcinomaJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2003ANNIE ON-ON CHAN Abstract Background and Aim: Decrease in expression of the E-cadherin,catenin complex is an important element in gastric carcinogenesis. However, the expression of the complex in gastric precancerous lesions has not been well studied. The present study aimed to examine the serial change in expression of E-cadherin,catenin complex in the precancerous lesions of gastric cancer patients. Methods: Gastrectomy specimens of 40 patients with gastric cancer were retrieved. Areas with chronic gastritis, atrophic gastritis, intestinal metaplasia and adenocarcinoma were identified and immunostained for ,-catenin, ,-catenin and E-cadherin. The results were scored semiquantitatively by two independent pathologists using a validated scoring system. Results: A significant decrease in score was observed in 5% (1/22) of ,-catenin, 0% (0/22) of ,-catenin and 9% (2/22) of E-cadherin in chronic atrophic gastritis patients, and in 28% (5/18) of ,-catenin, 67% (10/15) of ,-catenin and 57% (8/14) of E-cadherin in intestinal metaplasia patients. The scoring of ,-catenin, ,-catenin and E-cadherin correlated with each other. Forty-three percent of patients had concordant changes of scores along the gastritis,adenocarcinoma sequence. There was no association between Helicobacter pylori status and E-cadherin,catenin complex expression. Conclusion: Deregulation of the E-cadherin,catenin complex was observed in the majority of precancerous lesions in patients with gastric adenocarcinoma, which has potential diagnostic and therapeutic implications. © 2003 Blackwell Publishing Asia Pty Ltd [source] Differential expression of E-cadherin in metastatic lesionscomparing to primary oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 10 2006K.-F. Hung Background:, The main cause of treatment failure in resectable oral squamous cell carcinoma (OSCC) is metastasis. E-cadherin (E-cad) plays a principal role in cell adhesion and motility, and is associated with OSCC progression. The aim of this study was to investigate the clinical significance of E-cad expression in OSCC with lymph node metastasis which had radical neck dissection done. Method:, Immunohistochemistry was used to detect E-cad expression in normal oral mucosa (NOM) (n = 10), oral precancerous lesions (OPLs) (n = 20), primary OSCC (n = 45), and their paired metastatic lesions (n = 45). E-cad immunoreactivity correlated with the clinicopathologic features. Results:, E-cadherin immunoreactivity was progressively reduced in the NOM followed by OPLs and primary OSCC (58%). It decreased significantly in the advanced stages of OSCC. However, the increase in E-cad immunoreactivity was observed in the majority (60%) of metastatic lesions in relation to primary OSCC. Patients with such increased or positive immunoreactivity of E-cad in metastatic lesions exhibited worse prognosis. Conclusion:, The findings suggested a dynamic change in E-cad immunoreactivity during tumorigenesis and metastasis of OSCC. In a multivariate analysis, E-cad immunoreactivity in metastasis lesions (odds ratio 3.74, 95% CI 1.15,14.67; P = 0.040) implied the potential role of mortality predictors for OSCC cases with nodal involvement. [source] Increased survivin expression in high-grade oral squamous cell carcinoma: a study in Indian tobacco chewersJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 10 2006C. Jane Background:, Oral cancer is one of the five leading sites of cancer in the Indian population. In the present study we analyzed the expression of apoptosis regulating genes, viz. survivin, Bcl-2, Bax and p53 in precancerous and cancerous lesions of the buccal mucosa of Indian tobacco chewers. Method:, Paraffin-embedded tissue samples from 38 patients with primary oral squamous cell carcinoma (OSCC) and 17 patients with leukoplakia were used. The expression of survivin, Bcl-2, Bax, and p53 was evaluated using immunohistochemical staining method. Results:, Thirty-six percent OSCC were found to be positive for nuclear p53 staining while none of the precancerous lesions showed p53 positivity. Survivin, Bcl-2 and Bax expression was found to increase with increased grade of malignancy. Increase in survivin expression was statistically most significant (P < 0.001). Conclusion:, Increased expression of anti-apoptotic survivin in high-grade tumors suggests that survivin is likely to contribute significantly to apoptosis resistance in response to therapy. [source] Comparison of BrdU and cyclin A as markers of the S-phase in oral precancerous lesionsJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 9 2000Richard J. Oliver Abstract: A study comparing bromodeoxyuridine (BrdU) and cyclin A as markers of cells in the S-phase in oral precancerous lesions was performed. These were also compared with the growth fraction (GF) as assessed by Ki-67. Biopsies of 15 lesions were obtained, presenting clinically as leukoplakia or erythroplakia of the lateral tongue or floor of mouth. Half of each biopsy was incubated in BrdU and routinely fixed and processed. Sequential sections from each block were cut and stained immunohistochemically with antibodies against the following proteins: BrdU, Ki-67 and cyclin A. Stained sections were quantified and the labelling indices (LI) expressed per 100 of the total nucleated cell population (%) and per millimetre basement length (/mm). The mean LI% for BrdU was 11.24% (SD 2.83), for cyclin A it was 12.76% (SD 3.88) and the GF% was 29.25% (SD 11.88). The mean LI/mm for BrdU was 40.93/mm (SD 11.88), for cyclin A it was 47.59/mm (SD 18.28) and the GF/mm was 110.72/mm (SD 49.30). The BrdU and cyclin A indices were significantly correlated with each other. In the more dysplastic cases, the cyclin A LI was quantitatively much larger than that for BrdU, suggesting that the protein was being overexpressed. It was concluded that as a tool to study the kinetic aspects of the cell cycle in dysplastic lesions cyclin A was limited by the fact that it is overexpressed. In minimally dysplastic lesions and normal epithelia, however, cyclin A may be a viable alternative to BrdU for the study of the S-phase. [source] INK4a-ARF mutations in skin carcinomas from UV irradiated hairless miceMOLECULAR CARCINOGENESIS, Issue 4 2004N. Soufir Abstract To characterize further the role of the INK4a-ARF locus in the multistep process of skin carcinogenesis, we performed a mutational analysis of this locus in skin lesions from hairless mice either irradiated with UVB alone or with a solar simulator delivering UVA,+,B. INK4a-ARF mutations were present in five of 57 squamous cell carcinomas (9%), but no mutation was detected in precancerous lesions. All mutations were C:G,>,T:A transitions located at dipyrimidic sites, the hallmark of UVB mutagenesis. Three mutations affected only the p19ARF reading frame, whereas two mutations affected only the p16INK4a transcript. This study demonstrates for the first time UV-induced mutations of INK4a-ARF that occur in a small percentage in late stages skin tumors. © 2004 Wiley-Liss, Inc. [source] Renal carcinogenesis induced by ferric nitrilotriacetate in mice, and protection from it by Brazilian propolis and Artepillin CPATHOLOGY INTERNATIONAL, Issue 9 2000Tetsuo Kimoto The protective effect of Brazilian propolis and its extract Artepillin C against ferric nitrilotriacetate (Fe-NTA)-induced renal lipid peroxidation and carcinogenesis was studied in male ddY mice. Fe-NTA-induced renal lipid peroxidation leads to a high incidence of renal cell carcinoma (RCC) in mice. Administration of propolis by gastric intubation 2 h before or Artepillin C at either the same time, 2 h, or 5 h before the intraperitoneal injection of Fe-NTA (7 mg Fe/kg) effectively inhibited renal lipid peroxidation. This was evaluated from the measurement of renal thiobarbituric acid-reactive substances (TBARS) or histochemical findings of 4-hydroxy-2-nonenal (4-HNE)-modified proteins and 8-hydroxy-2, -deoxyguanosine (8-OHdG). Repeated injection of Fe-NTA (10 mg Fe/kg per day, twice a week for a total of 16 times in 8 weeks) caused subacute nephrotoxicity as revealed by necrosis and pleomorphic large nuclear cells in the renal proximal tubules, and gave rise to RCC 12 months later. A protective effect from carcinogenicity was observed in mice given propolis or Artepillin C. Furthermore, the mice given Fe-NTA only developed multiple cysts composed of precancerous lesions with multilayered and proliferating large atypical cells. Mice treated with propolis and Artepillin C also had cysts, but these were dilated and composed of flat cells. These results suggest that propolis and Artepillin C prevent oxidative renal damage and the carcinogenesis induced by Fe-NTA in mice. [source] Treatment of Laryngeal Carcinomas by Laser Endoscopic Microsurgery ,THE LARYNGOSCOPE, Issue 6 2000Pierre R. Moreau MD Abstract Objectives To determine if laser endoscopic microsurgery is a reliable and appropriate approach in the treatment of laryngeal cancers. Study Design Retrospective study of 160 patients treated from 1988 to 1996 at Liège. Analysis of indication, technique, and oncologic results. Methods Glottic tumors were treated with either type I, type II, or type III cordectomy, with or without conservation of an inferior muscular band, and extended if necessary to all or part of the contralateral cord. For supraglottic cancers, an excision limited to a part of the vestibule, a trans-preepiglottic resection, or a radical supraglottic resection was carried out. Results Our corrected actuarial survival at 5 years was 97% for the 98 infiltrative glottic tumors and 100% for the 18 infiltrative supraglottic and 27 in situ carcinomas. No local recurrences were noted, in either the group of 118 infiltrating cancers (in whom two precancerous lesions were treated with a further laser excision), or in the 27 in situ carcinomas. Local control was thus 100%. One patient died of his cancer, with lung metastases after neck recurrence. Conclusions Like Steiner and Rudert, this series demonstrates the oncologic validity of this surgical approach to the treatment of unadvanced glottic tumors. Unlike these authors' study, however, strict case selection, as in cases with significant involvement of the anterior commissure, has allowed us to avoid local recurrences and consequently to avoid salvage total laryngectomies. Our experience with supraglottic cancers is too small to confirm the oncologic validity of this type of surgery but seems promising. [source] Autofluorescence spectroscopy for the diagnosis of cervical intraepithelial neoplasiaBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 8 2002Helmut Weingandt Objective To assess the feasibility of autofluorescence spectroscopy in the diagnosis of cervical intraepithelial neoplasia (CIN) using broadband light excitation. Design Feasibility study. Setting Colposcopy clinic of an university hospital. Population Sixty-eight patients at risk for CIN. Methods After excitation with a broadband light between 375 and 440 nm, spectral distribution of native tissue fluorescence (autofluorescence) was acquired from 685 cervical sites for the localisation and differentiation of CIN, and compared with colposcopically directed biopsy and human papillomavirus (HPV) DNA testing. Main outcome measure Detection of CIN. Results The evaluation of spectral measurements revealed significantly lower autofluorescence values for CIN 3 lesions compared with normal tissue (P < 0.001), and compared with CIN 1 or CIN 2 (P < 0.002). High grade CIN lesions (CIN 2/3) presented with a significant reduced autofluorescence compared with CIN 1 (P < 0.002). Patients with a positive HPV DNA testing showed a significantly lower autofluorescence than patients tested negative for HPV DNA (P < 0.05). Severe inflammation such as chronic cervicitis may lead to false positive results. Conclusions Autofluorescence spectroscopy represents an interesting approach for the detection of cervical neoplasia. Using an excitation wavelength band between 375 and 440 nm, significant differences between normal and precancerous lesions of the cervix can be seen. [source] Inactivation of the CDKN2A and the p53 tumour suppressor genes in external genital carcinomas and their precursorsBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2007N. Soufir Summary Background, p53 has been extensively studied in external genital carcinoma (EGC), and is frequently inactivated, but little is known about the role of the CDKN2A tumour suppressor gene in the oncogenesis of EGC. Objectives, To investigate the role of CDKN2A and p53 in the pathogenesis of EGCs and their precursor lesions vulval intraepithelial neoplasia (VIN3), penile intraepithelial neoplasia and lichen sclerosus (LS). Methods, By means of CDKN2A and p53 mutation screening (single-strand conformational polymorphism analysis and sequencing), methylation analysis of alternative CDKN2A promoters (methylation-specific polymerase chain reaction) and p53 immununochemistry, we analysed eight invasive EGCs (five from vulva and three from penis) and 25 precancerous lesions (two undifferentiated VIN3 and 23 vulval/penile lesions of LS) from 33 patients. Results, p53 mutations (mainly transversions) and CDKN2A mutations (including one hot spot) were present in 75% and 50% of invasive tumours, respectively, but were absent in all precancerous lesions. Remarkably, all CDKN2A -mutated tumours also harboured a p53 mutation. CDKN2A or p53 mutations were observed more frequently in LS-derived EGCs than in human papillomavirus-derived EGCs (P = 0·053). A positive anti-p53 staining, but without p53 mutations, was also detected in 30% of LS lesions, suggesting a p53 stabilization in response to inflammation and carcinogenic insult. Methylation of p16INK4a and p14ARF promoters was not a frequent mechanism of CDKN2A inactivation. Conclusions, Our study shows a high prevalence of co-inactivating mutations of p53 and/or CDKN2A genes in EGC, that seem to occur preferentially in LS-derived tumours and late in oncogenesis. [source] Community-based multiple screening model,,§¶CANCER, Issue 8 2004387 participants Taiwan community-based integrated screening group, Design, analysis of 4, implementation Abstract BACKGROUND Multiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow-up. METHODS An integrated model of community-based multiple screening was designed and conducted between 1999 and 2001 in Keelung, Taiwan. The authors used a Papanicolaou (Pap) smear screening program as a base to integrate other screening regimens encompassing four other neoplastic diseases and three nonneoplastic chronic diseases. Screening methods, the interscreening interval, and the follow-up for each screening regimen were designed based on evidence-based literature and current national screening policy. RESULTS A total of 42,387 subjects participated in the screening activities. A 25% increase in the attendance rate for Pap smear screening was demonstrated after the introduction of multiple disease screening programs. At the first screen, this program yielded a total of 677 asymptomatic neoplasms (16.0 per 1000), including a large proportion of precancerous lesions and small presymptomatic tumors without lymph node involvement. The association between the occurrence of neoplasm and the presence of comorbid nonneoplastic chronic disease was found to be statistically significant (odds ratio, 1.64; 95% confidence interval, 1.38,1.94 [P < 0.05]). The authors also identified 5314 subjects with metabolic syndrome who were at a greater risk for colorectal and oral neoplasias. CONCLUSIONS The results of the current study demonstrate that an outreach and community-based multiple screening program not only enhances attendance rates but also has a high yield of early cases of various diseases simultaneously, and provides a natural opportunity to elucidate the correlation between neoplastic disease and nonneoplastic chronic disease. Cancer 2004. © 2004 American Cancer Society. [source] Hexosaminidase-altered Aberrant Crypts, Carrying Decreased Hexosaminidase , and , Subunit mRNAs, in Colon of 1,2-Dimethylhydrazine-treated RatsCANCER SCIENCE, Issue 2 2001Tetsuya Tsukamoto Aberrant crypt foci (ACF), consisting of morphologically irregular crypts, are thought to be precancerous lesions for colon cancers. For their molecular analysis, it is necessary to avoid contamination with adjacent normal crypts and stromal cells. Decreased hexosaminidase activity in ACF, which has been histochemically demonstrated, was used in the present study to classify isolated crypts in combination with morphological changes. The length, rim diameter, and width (average±SD, ,m) of hexosaminidase-positive (Hex+) crypts were 238.6±40.4, 89.5±22.9, and 57.6±14.0, respectively. For hexosaminidase-negative (Hex-) crypts, the values were 314.4±77.8, 140.3±45.7, and 97.3±34.7, the width being 1.69 tunes greater (P<0.0001). Crypts wider than 115 ,m (approximately 2 tunes the average size of Hex+ crypts) were all from ACF, judging from hexosaminidase staining. To analyze transcription levels of Hex , and , subunits (Hexa and Hexb, respectively), real-tune relative quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed using the LightCycler system. In aberrant crypts, both Hexa and Hexb were significantly down-regulated to 0.266 (P<0.002) and 0.131 (P<0.001) units, respectively, compared with those in morphologically normal crypts, with , -actin as the internal standard. This decrease could be a molecular marker for precancerous enzyme-altered ACF. [source] | |||||||||||||||||||||||||