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Histologic Grade (histologic + grade)

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Medical Sciences	96%

Selected Abstracts

Histologic grade, stage, and survival in breast carcinoma,,

CANCER, Issue 5 2003
Caucasian women, Comparison of African American
Abstract BACKGROUND African American women have lower breast carcinoma survival rates than do Caucasian women. African American women often present with advanced-stage disease and more aggressive tumors as shown by histologic and laboratory-based prognostic factors. Aggressive tumor behavior may be responsible, at least in part, for the advanced stage and reduced survival rates. METHODS The authors investigated the correlation between survival and histologic grade, stage of disease, and tumor size for both African American and Caucasian women who were younger than age 50 years and age 50 years and older. The authors also investigated the distribution of grade within each stage group and the distribution of grade by tumor size. African American and Caucasian women were matched by stage, tumor size, and histologic grade. Survival was represented by 6-year breast carcinoma,specific survival rates. RESULTS Compared with Caucasian women, African American women, regardless of age, had proportionally more Grade III tumors and fewer Grade I and II tumors for all stages combined and for each individual stage group. Similarly, matched for tumor size, African American women had more Grade III tumors and fewer Grade I and II tumors compared with Caucasian women, except for tumors smaller than 1.0 cm. For nearly all combinations of stage and grade regardless of age, the 6-year breast carcinoma,specific survival rate was lower for African American women than for Caucasian women, although it did not always reach statistical significance. CONCLUSIONS Compared with Caucasian women, African American women, regardless of age, presented with proportionally more aggressive tumors for each stage of disease and for each tumor size above 1.0 cm as revealed by the histologic grade. Higher histologic grade may be a significant contributing factor to survival disadvantage for African American women. Cancer 2003;98:908,17. Published 2003 by the American Cancer Society. DOI 10.1002/cncr.11558 [source]

How much does Gleason grade of follow-up biopsy differ from that of initial biopsy in untreated, Gleason score 4,7, clinically localized prostate cancer?

THE PROSTATE, Issue 15 2007
R. Choo
Abstract OBJECTIVE To compare histologic grades between an initial biopsy and a follow-up biopsy in untreated, Gleason score (GS) 4,7, clinically localized prostate cancer. METHODS AND MATERIALS In a prospective single-arm cohort study, clinically localized, GS 4,7, prostate cancer was managed with active surveillance alone, provided that a pre-defined definition of disease progression was not met. One hundred five (63%) of a total of 168 eligible patients underwent a follow-up prostate biopsy during surveillance. Median time to a follow-up biopsy was 22 months (range: 7,81). Histologic grades between these two biopsies were compared to evaluate the extent of histologic grade change. RESULTS On the follow-up biopsy, GS was unchanged in 33 patients (31%), upgraded in 37 (35%), and downgraded in 34 (32%). Eleven (10%) had upgrading by 2 Gleason points or more. Eight (8%) had upgrading to GS 8 (none to GS 9 or 10); of these, six were among those with upgrading by 2 Gleason points or more. Twenty-seven (26%) had no malignancy on the follow-up biopsy. Negative follow-up biopsy was more prevalent in patients with a small volume of malignancy in the initial biopsy and a low baseline PSA. CONCLUSIONS No consistent change in histologic grade was observed on the follow-up biopsy at a median of 22 months in untreated, GS 4,7, clinically localized prostate cancer. Upgrading to GS ,8 or by 2 Gleason points or more was relatively uncommon. Prostate 67: 1614,1620, 2007. © 2007 Wiley-Liss, Inc. [source]

Subgrouping and grading of soft-tissue sarcomas by fine-needle aspiration cytology: A histopathologic correlation study

DIAGNOSTIC CYTOPATHOLOGY, Issue 5 2001
Hal E. Palmer M.D.
Abstract To evaluate the accuracy and reproducibility of subgrouping and grading soft-tissue sarcomas by fine-needle aspiration biopsy (FNAB), a blind review was conducted of 84 FNAB specimens from 77 malignant and 7 benign soft-tissue lesions. Cytomorphologic subgroups included 31 spindle-cell, 24 pleomorphic, 11 myxoid, 7 epithelioid/polygonal, 3 small round cell, and 8 nondiagnostic cases. Malignancies included one lymphoma and 41 primary, 15 recurrent, and 20 metastatic soft-tissue sarcomas. Adequacy was defined as a majority of slides with at least 5 clusters of 10 unobscured cells. Five originally false-negative cases were considered nondiagnostic on review. Sarcoma was recognized in 59 of 64 adequate cases (92%) with available histology; however, the specific histopathologic subtype was identified in only 9 cases (14%). Benign myxoid and spindle-cell lesions were difficult to separate from low-grade sarcomas in 4 cases, and a B-cell lymphoma with sclerosis mimicked a low-grade myxoid sarcoma. The assigned cytologic grade accurately reflected the histologic grade in 90% of sarcomas when segregated into high and low grades. Pleomorphic, small round cell, and epithelioid/polygonal subgroups corresponded to high-grade sarcomas in all cases with only minor noncorrelations. Major grading noncorrelations occurred in 50% of myxoid and 9% of spindle-cell sarcomas. Therefore, attention should be given to specimen adequacy, and caution should be exercised when attempting to grade myxoid and spindle-cell sarcomas by FNAB. Diagn. Cytopathol. 24:307,316, 2001. © 2001 Wiley-Liss, Inc. [source]

Screening for local and regional cancer recurrence in patients curatively treated for laryngeal cancer: Definition of a high-risk group and estimation of the lead time

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2007
Savitri C. Ritoe MD
Abstract Background. All patients treated for laryngeal cancer are offered the same follow-up schedule to detect asymptomatic locoregional recurrences. In this study, we evaluated the prognostic profile of patients for cancer recurrence and estimated the lead time. Methods. A cohort study was performed between 1990 and 1995. Cox proportional hazards model was used to analyze the prognostic factors. The effect of altering the follow-up for asymptomatic recurrence detection was determined after estimating the lead time. Results. The variables cT classification, smoking, and histologic grade proved to be prognostic factors. The risk of locoregional failure was 15% in the low-risk group versus 29% in the high-risk group. The estimated lead time was 2 to 4 weeks. Conclusion. Risk profiles for locoregional relapse were defined. Intensifying the follow-up schedule is not advisable because the lead time is very short. An excessively high number of routine visits would have to be performed to increase the detection rate for asymptomatic recurrences. © 2006 Wiley Periodicals, Inc. Head Neck, 2007 [source]

Risk factors for late cervical lymph node metastases in patients with stage I or II carcinoma of the tongue

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2002
Hideo Kurokawa DDS
Abstract Background Many histopathologic parameters in squamous cell carcinoma of the tongue have been identified as predictive factors for cervical lymph metastasis. However, predictive factors for occult cervical lymph node metastases and the criterion for elective therapy remain inconclusive. This study analyzed the clinicopathologic factors associated with late cervical lymph node metastases in patients with carcinoma of the tongue. Methods The clinicopathologic features of 50 consecutive patients seen between January 1985,December 1996 with previously untreated stage I or II squamous cell carcinoma of the tongue were reviewed. All patients were treated with partial glossectomy without elective neck dissection. Their mean age was 54.5 y (range, 23,90 y) and the male,female ratio was 1.2:1 (27 men and 23 women); 30 cases were stage I, and 20 cases were stage II. Clinicopathologic factors were analyzed to determine factors predicting late cervical lymph node metastasis. Results The overall cervical lymph node metastasis rate was 14.0% (7 of 50). Clinicopathologic factors significantly associated with the development of cervical lymph node metastasis were tumor size (,30 mm), tumor depth (,4 mm), differentiation, mode of invasion, microvascular invasion, and histologic grade of malignancy. In a multivariate logistic regression analysis, moderately differentiated squamous cell carcinoma of the tongue with tumor depth ,4 mm had predictive value for late cervical lymph node metastasis and diminished overall survival (odds ratio, 10.0; p = .02; hazards ratio, 7.0; p = .039). Conclusions The findings of this study demonstrate tumor depth ,4 mm moderately differentiated squamous cell carcinoma of the tongue have a substantially higher rate of late cervical metastases. In the basis of these data, it is our recommendation that this be used in the decision to electively treat the neck. © 2002 Wiley Periodicals, Inc. Head Neck 24: 731,736, 2002 [source]

Magnetic Resonance Imaging of Focal Splenic and Hepatic Lesions in the Dog

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2004
Craig A. Clifford
Focal hepatic and splenic lesions in the dog are common, and approximately half of such lesions are malignant. Both incidentally discovered lesions and lesions in patients with known malignancies represent diagnostic dilemmas. Ultrasound often fails to characterize such lesions adequately. This uncertainty may result in unnecessary splenectomies and liver biopsies for benign lesions or noncurative surgery for advanced-stage malignancies. In humans, ultrasound largely has been supplanted by computed tomography and magnetic resonance imaging (MRI) for the characterization of focal hepatic and splenic lesions. The inherently high soft tissue contrast of MRI allows the differentiation of benign from malignant hepatic and splenic lesions in the human patients. In this prospective study, 35 focal lesions of either the spleen (n = 8) or the liver (n = 27) were characterized by MRI in 23 dogs. Lesions were presumptively classified as malignant or benign on the basis of MRI findings. Imaging results then were correlated with histopathologic (29) or cytologic (6) evaluation of the lesions. The overall accuracy in differentiating malignant from benign lesions was 94% (33 of 35 lesions). The overall sensitivity and specificity were 100% (95% CI, 78,100%) and 90% (95% CI, 68,99%), respectively. MRI classified malignant hepatic lesions as hepatocellular carcinoma (HCC) in all confirmed cases and correctly predicted the histologic grade of 5 HCC lesions. These results suggest that MRI is a useful modality for abdominal imaging in veterinary patients, and MRI accurately differentiated benign from malignant focal hepatic and splenic lesions in this sample of patients. [source]

Liver transplantation in association with hepatocellular carcinoma: An update of the international tumor registry

LIVER TRANSPLANTATION, Issue 9 2002
Ernesto P. Molmenti
Hepatocellular carcinoma is an epithelial tumor derived from hepatocytes that accounts for more than 80% of all primary hepatic tumors. The severity of the underlying disease is almost always the key factor in deciding whether to consider liver resection or transplantation as its treatment. Data in our registry corresponding to almost 800 patients from transplant centers throughout the world showed that patient survival after liver transplantation was significantly affected by histologic grade, tumor size >5 cm, and the presence of positive nodes. Recurrence-free survival showed a correlation with tumor size >5 cm, positive nodes, bilobar spread, and vascular invasion. At the present time, 59% of patients in our registry are alive, 84% of whom are free of tumor. Of those who died, half did so without evidence of tumor. [source]

Occult Metastases in Axillary Lymph Nodes as a Predictor of Survival in Node-Negative Breast Carcinoma with Long-term Follow-up

THE BREAST JOURNAL, Issue 3 2004
Wenche Reed MD
Abstract: Increased detection rate in the lymph nodes is seen with serial sectioning or immunohistochemistry (IHC), but the importance of occult metastases is not resolved. IHC is still not recommended in routine examination of lymph nodes. Axillary lymph nodes from 385 node-negative breast cancer patients with a median follow-up of 25 years were examined with IHC for cytokeratins, applied on routine sections. The association between classic histopathologic prognostic factors and the presence of occult metastases was evaluated. Metastases were found in 45 of 385 cases (12%), 21 metastases (47%) measured ,0.2 mm, 8 (18%) were larger than 2 mm; 14 metastases were located in the subcapsular sinus, 22 in the parenchyma of the lymph node; and 51% (23/45) of the metastases were recognized on hematoxylin-eosin staining on "second look." The detection of metastases was significantly associated with the number of sectioned lymph nodes (6% metastases for one to five lymph nodes examined versus 17% for more than five lymph nodes) and with histologic subtype (metastases in 11% of the ductal versus 33% of the lobular carcinomas). No significant association was found between occult metastases and age, tumor size, histologic grade, estrogen or progesterone receptor status, p53, or c- erbB-2. Metastases larger than 2 mm predicted a poorer recurrence-free survival rate for the whole series. A subcapsular location of the metastases was a strong predictor of overall survival. Whether or not the metastases could be identified on hematoxylin-eosin sections did not have any prognostic significance. In the multivariate analysis, histologic grade, tumor size of the primary tumor, progesterone receptor status, and the presence of occult metastasis in the lymph nodes had a prognostic impact on survival with a 25-year follow-up. [source]

How much does Gleason grade of follow-up biopsy differ from that of initial biopsy in untreated, Gleason score 4,7, clinically localized prostate cancer?

Expression of ezrin, Bcl-2, and Ki-67 in chondrosarcomas

APMIS, Issue 10 2010
MIRVA SÖDERSTRÖM
Söderström M, Palokangas T, Vahlberg T, Böhling T, Aro H, Carpen O. Expression of ezrin, Bcl-2, and Ki-67 in chondrosarcomas. APMIS 2010; 118: 769,76. The aim of the present study was to investigate whether the expression of ezrin, a membrane-cytoskeleton linker and regulator of cellular signaling, is associated with clinical features of chondrosarcoma. For this purpose, we studied the expression of ezrin in 54 chondrosarcomas by immunohistochemistry and correlated the expression with other tumor characteristics, markers of proliferation, apoptosis and with clinical parameters. The intensity of ezrin staining increased with the histologic grade, and a significant positive association existed between the tumor grade and ezrin expression (p = 0.0475). In addition, there was a positive correlation between the expression of ezrin and Bcl-2, an anti-apoptotic protein (r = 0.83, p < 0.0001), as well as between ezrin expression and increased proliferation as measured by Ki-67 index (r = 0.70, p < 0.0001). The positive correlation of ezrin expression with Bcl-2 and Ki-67 as well as with tumor grade suggests that an aggressive behavior of chondrosarcoma may be related to activation of ezrin and that ezrin inhibitors could provide a much needed adjuvant therapy in chondrosarcomas. In conclusion, our results indicate that high ezrin expression correlates with aggressive features of chondrosarcomas. Further analyses on the pathways downstream of ezrin are warranted. [source]

Anti-angiogenic factor endostatin in osteosarcoma

APMIS, Issue 10 2009
HYUN-SOO KIM
Neoplastic neovascularization is regulated not only by stimulators, but also by inhibitors of angiogenesis and might be the result of a net balance between the positive and negative regulators. Endostatin (ES) is a potent inhibitor of angiogenesis. The expression of ES has not been investigated in patients with osteosarcomas (OSAs). The aim of this study was to determine whether there is a correlation between the expression of ES and clinicopathologic parameters and/or outcomes in patients with OSAs. We made tissue microarrays from 46 cases of OSA and analyzed the expression of ES using immunohistochemistry. Staining was assessed in a semi-quantitative manner by scoring the proportion of positive tumor cells over the total number of tumor cells. A sample was defined as ES-positive when 10% or more of the tumor cells were stained positively throughout the tumor core. ES was localized to the cytoplasm of the tumor cells. 32.6% (15/46) of the patients were ES-positive. The expression of ES was positively correlated with tumor size (p = 0.011), histologic grade (p = 0.034), stage (p = 0.025), and distant metastasis (p = 0.036). Our results suggest that the expression of ES is increased in OSA, and ES may be used as a prognostic marker in patients with OSAs. [source]

Overexpression of cyclooxygenase-2 in urothelial carcinoma in conjunction with tumor-associated-macrophage infiltration, hypoxia-inducible factor-1, expression, and tumor angiogenesis

APMIS, Issue 3 2009
WAN-TZU CHEN
This study examines whether the expression of cyclooxgenase-2 (COX-2) in urothelial carcinoma (UC) is associated with macrophage infiltration, hypoxia-inducible factor-1, (HIF-1,) expression and angiogenesis. We investigated the expression of COX-2 associated with HIF-1, and performed double immunohistochemical analysis of 216 UCs for COX-2 expression and the correlation with tumor-associated-macrophage (TAM) density and microvessel density (MVD) in situ. A high expression of COX-2 was positively correlated with tumor invasiveness, histologic grade and HIF-1, expression in UC (p<0.0001, p=0.003, p<0.0001, respectively). Quantification of double staining of COX-2/CD34 and COX-2/CD68 showed that a higher MVD and TAM density was found in COX-2 high-expression than in COX-2 low-expression tumor fields (p<0.0001). Adjacent to the principal of COX-2 expression areas, MVD value and TAM density were significantly increased in HIF-1, high-expression specimens compared with HIF-1, low-expression ones (p<0.0001). Interestingly, our data revealed that high COX-2 expression (p=0.002), high HIF-1, expression (p<0.0001) and TAM density (p<0.0001) were all associated with high MVD value. Our results suggest that COX-2 may produce a cooperative effect in promoting tumor progression and may be involved in the process of angiogenesis through increasing TAM infiltration or HIF-1, regulation by hypoxia. [source]

Frequency of the basal-like phenotype in African breast cancer,

APMIS, Issue 12 2007
HAWA NALWOGA
Basal-like breast carcinoma has been recognized as a subtype with specific prognostic implications. However, there is a lack of reports about this category of breast tumors in African women. The aim of this study was to explore the basal-like phenotype in breast cancer patients in an African population, and a registry-based series was included from the well-defined Kyadondo County in Uganda (1.7 millions). We studied a total of 65 archival paraffin blocks of invasive breast cancer using antibodies against cytokeratin 5/6 and P-cadherin, and these markers were expressed in 34% of all cases and in 52% of ER (estrogen receptor)-negative tumors. All basal-like tumors were ER negative (p<0.0005) and PR (progesterone receptor) negative (p=0.002). Basal-like breast carcinomas were of a higher histologic grade (p=0.001), had high mitotic counts (p=0.002), and marked nuclear pleomorphism (p=0.002). P-cadherin-positive tumors had a high Ki-67 proliferative rate (p=0.039). In conclusion, the basal-like phenotype is frequent in this African series of breast cancer and is strongly associated with poor prognostic factors. Our findings might be significant in relation to clinical management of these patients, including novel targeted therapy. [source]

Significance of CD 105 expression for tumour angiogenesis and prognosis in endometrial carcinomas

APMIS, Issue 11 2003
HELGA B. SALVESEN
Angiogenesis is a key process in tumour growth and metastasis, and Factor-VIII microvascular density has been found to influence prognosis among endometrial carcinoma patients. The CD105/endoglin antibody has been reported to preferentially bind to activated endothelial cells in tissues participating in angiogenesis, and we therefore wanted to compare the prognostic significance of CD105/endoglin to that of Factor-VIII. In a population-based endometrial carcinoma study with long (median 11.5 years) and complete patient follow-up, mean intratumour microvascular density (MVD) assessed using CD105/endoglin was investigated and compared with previous data for MVD assessed using Factor-VIII. MVD by CD105/endoglin was significantly correlated with MVD by Factor-VIII (p=0.001). However, tumours within the two groups defined by the upper and lower quartiles for CD105/endoglin-MVD were both significantly more often metastatic (FIGO-stage III/IV; p=0.03), with high tumour cell proliferation by Ki67 (p=0.007) and with reduced survival (p=0.036) as compared with the intermediate groups. In Cox regression analysis, CD105/endoglin-MVD showed independent prognostic influence when analysed together with patient age, FIGO stage, histologic subtype, histologic grade and Factor-VIII-MVD, while the latter lost its prognostic impact when CD105/endoglin was included. In the subgroup with high MVD, there was a tendency towards improved response to radiation therapy. In conclusion, CD105/endoglin-MVD is significantly associated with FIGO stage, tumour proliferation and prognosis in endometrial carcinoma, indicating that this is a better angiogenic marker in these tumours. [source]

Molecular pathogenesis and prognostic factors in endometrial carcinoma

APMIS, Issue 10 2002
HELGA B. SALVESEN
Endometrial carcinoma is today among the most common gynecologic malignancies in industrialized countries. In order to improve the treatment and follow-up of these patients, various prognostic factors have been extensively studied. Patient age, stage of disease, histologic type and histologic grade have been shown to influence survival significantly, and the prognostic impact of these traditional clinicopathologic variables is well established. In addition, parity, hormone receptor concentration in the tumor, DNA ploidy and morphometric nuclear grade have all been found to influence prognosis. Information about DNA ploidy has especially been used in the clinical situation to determine individualized treatment. The prognostic significance of markers for tumor cell proliferation, cell cycle regulation (p53, p21 and p16) and angiogenesis is discussed as well as the molecular basis of endometrial carcinoma. In conclusion, several prognostic markers have been identified. It is likely that the information derived from these tumor biomarkers will reduce the need for extensive surgical staging and adjuvant treatment in endometrial carcinoma. [source]

Model-based prediction of defective DNA mismatch repair using clinicopathological variables in sporadic colon cancer patients

CANCER, Issue 7 2010
Frank Sinicrope MD
Abstract BACKGROUND: Colon cancers with defective DNA mismatch repair (MMR) have a favorable prognosis and may lack benefit from 5-fluorouracil,based adjuvant chemotherapy. The authors developed models to predict MMR deficiency in sporadic colon cancer patients using routine clinical and pathological data. METHODS: TNM stage II and III colon carcinomas (n = 982) from 6 5-fluorouracil,based adjuvant therapy trials were analyzed for microsatellite instability and/or MMR protein expression. Tumor-infiltrating lymphocytes (TILs) were quantified (n = 326). Logistic regression and a recursive partitioning and amalgamation analysis were used to identify predictive factors for MMR status. RESULTS: Defective MMR was detected in 147 (15%) cancers. Tumor site and histologic grade were the most important predictors of MMR status. Distal tumors had a low likelihood of defective MMR (3%; 13 of 468); proximal tumors had a greater likelihood (26%; 130 of 506). By using tumor site, grade, and sex, the logistic regression model showed excellent discrimination (c statistic = 0.81). Proximal site, female sex, and poor differentiation showed a positive predictive value (PPV) of 51% for defective MMR. In a patient subset (n = 326), a model including proximal site, TILs (>2/high-power field), and female sex showed even better discrimination (c statistic = 0.86), with a PPV of 81%. CONCLUSIONS: Defective MMR is rare in distal, sporadic colon cancers, which should generally not undergo MMR testing. Proximal site, poor differentiation, and female sex detect 51% of tumors with defective MMR; substituting TILs for grade increases the PPV to 81%. These data can increase the efficiency of MMR testing to assist in clinical decisions. Cancer 2010. © 2010 American Cancer Society. [source]

The role of postoperative radiotherapy for the treatment of gangliogliomas

CANCER, Issue 2 2010
Dirk Rades MD
Abstract BACKGROUND: Because of their rarity, no prospective studies have been performed regarding gangliogliomas. The optimal treatment regimen is unclear. In this study, the authors compared 4 therapies for local control (LC) and overall survival (OS) in patients with ganglioglioma. METHODS: In 402 patients with ganglioglioma, outcomes were compared for patients who underwent gross total resection alone (GTR) (n = 188), GTR plus radiotherapy (GTR + RT) (n = 21), subtotal resection alone (STR) (n = 113), and STR plus RT (STR + RT (n = 80). Age, sex, tumor site, and histologic grade also were investigated. Subgroup analyses were performed for both low-grade and high-grade tumors. RESULTS: The 10-year LC rates were 89% after GTR, 90% after GTR + RT, 52% after STR, and 65% after STR + RT (P < .001); and the 10-year OS rates were 95%, 95%, 62%, and 74%, respectively (P < .001). After STR, irradiation significantly improved LC (P = .004) but not OS (P = .22). After GTR, irradiation did not significantly improve LC (P = .23) or OS (P = .29). On multivariate analyses, LC and OS were associated with therapy and pathologic grade, and OS also was associated with tumor site. In low-grade tumors, STR + RT resulted in better LC (P = .016) but not better OS (P = .18); and, after GTR, LC (P = .28) and OS (P = 1.0) were not improved with postoperative radiotherapy. In high-grade tumors, STR + RT resulted in better LC (P = .016) but not better OS (P = .41); after GTR, LC (P = .56) and OS (P = .61) were not improved with irradiation. CONCLUSIONS: According to this review, GTR should be performed whenever safely possible and does not require postoperative irradiation. If only STR is achieved, then RT improves LC of both low-grade and high-grade tumors and, thus, should be considered seriously. Cancer 2010. © 2010 American Cancer Society. [source]

Treatment and survival outcomes based on histologic grading in patients with head and neck mucoepidermoid carcinoma

CANCER, Issue 8 2008
Melonie A. Nance MD
Abstract BACKGROUND. Histopathologic grade of mucoepidermoid carcinoma (MEC) is an established predictor of prognosis and affects treatment protocol. Tumor behavior is more aggressive in high-grade than in low-grade MEC, leading to a more intensive treatment protocol. Outcomes for patients with intermediate-grade MEC are less clear; therefore, the optimal treatment protocol for this group is not well defined. The treatment protocol and survival outcomes of patients treated for MEC of the head and neck was investigated. METHODS. A retrospective clinical review and prospective review of histopathologic grading were undertaken using the most recently established grading system of 50 patients with MEC of the head and neck from 1983 through 2004. RESULTS. As histologic grade increased from low to intermediate to high, overall survival (P < .0001) and disease-free survival (P < .001) were significantly decreased. Overall and disease-free survival were significantly better for patients with intermediate-grade MEC than those with high-grade disease. Overall and disease-free survival were similar for patients with low-grade and intermediate-grade MEC. There was a low rate of disease recurrence in patients with intermediate-grade MEC, but this did not lead to death from disease. Although no patients with low-grade or intermediate-grade MEC died of disease, 52% of patients with high-grade MEC died of disease. Multivariate analysis revealed that histologic grade, age, and surgical margin status significantly predicted prognosis. CONCLUSIONS. These findings suggest that, under the current histopathologic classification system, the behavior of intermediate-grade MEC is comparable to that of low-grade MEC and different from high-grade MEC, allowing for the establishment of an evidence-based treatment protocol. Cancer 2008. © 2008 American Cancer Society. [source]

Prognostic significance of Wilms tumor gene (WT1) mRNA expression in soft tissue sarcoma

CANCER, Issue 10 2006
Tsukasa Sotobori M.D.
Abstract BACKGROUND There have been several recent reports that Wilms tumor gene (WT1) mRNA is overexpressed in many types of neoplasms, and those results suggested that WT1 has oncogenic properties. The objective of the current study was to evaluate the prognostic significance of WT1 mRNA expression in patients with soft tissue sarcoma. METHODS Levels of WT1 mRNA expression were examined by quantitative, real-time reverse transcriptase-polymerase chain reaction analysis in frozen tissue samples from 52 patients with soft tissue sarcoma. Various clinicopathologic factors were analyzed along with the disease-specific survival rate for correlations with WT1 mRNA expression levels. RESULTS The levels of WT1 mRNA expression in a variety of soft tissue sarcomas were significantly greater compared with the levels in normal soft tissue samples (P = .0212). No significant correlation was observed between the level of WT1 mRNA expression and clinicopathologic factors, including gender, age, primary tumor site, tumor depth, tumor size, histologic grade, and distant metastasis at initial presentation. The disease-specific survival rate for patients with high WT1 mRNA expression levels was found significantly poorer compared with the rate for patients with low WT1 mRNA expression levels (P = .0182). Moreover, multivariate analysis indicated that a high WT1 mRNA expression level was an independent, adverse prognostic factor for disease-specific survival (hazards ratio, 2.6; P = .0488). CONCLUSIONS WT1 mRNA expression level can serve as a potent prognostic indicator in soft tissue sarcoma patients. Cancer 2006. © 2006 American Cancer Society. [source]

Prognostic factors in the nonsurgical treatment of esophageal carcinoma with radiotherapy or radiochemotherapy

CANCER, Issue 8 2005
The importance of pretreatment hemoglobin levels
Abstract BACKGROUND The current study was performed to evaluate prognostic factors for overall survival (OS), distant metastasis (DM), and local failure (LF) in patients with Stage II/III esophageal carcinoma. METHODS The following potential prognostic factors were retrospectively investigated in 124 patients treated with radiotherapy (RT) alone or with radiochemotherapy: age, gender, performance status, tumor location, tumor length, histology, histologic grade, T classification, N classification, International Union Against Cancer stage, chemotherapy, RT dose, and pre-RT hemoglobin level. RESULTS Using univariate analysis (Kaplan,Meier method), pre-RT hemoglobin level, RT dose, tumor length, chemotherapy, and performance status were significantly associated with OS. Hemoglobin levels of 12.1,14.0 g/dL were associated with the best OS, followed by , 14.1 g/dL and , 12.0 g/dL. DM was significantly influenced by tumor length, RT dose, N classification, and performance status. LF was significantly influenced by pre-RT hemoglobin level, RT dose, and tumor length. Using multivariate analysis (Cox proportional hazard model), pre-RT hemoglobin maintained significance for OS (P < 0.001) and LF (P < 0.001), RT dose for OS (P = 0.001), DM (P = 0.031), and LF (P < 0.001), tumor length for OS (P = 0.003), DM (P = 0.017), and LF (P = 0.033), and chemotherapy for OS (P = 0.027). N classification was of borderline significance for DM (P = 0.054). Performance status lost significance for OS (P = 0.73) and LF (P = 0.22). CONCLUSIONS The strongest predictors for outcome in Stage II/III esophageal carcinoma were RT dose, tumor length, pre-RT hemoglobin level, and chemotherapy. The pre-RT hemoglobin level was an independent prognostic factor significantly associated with OS and LF. A hemoglobin level of 12.1,14 g/dL resulted in a better prognosis than hemoglobin levels , 14 g/dL and , 12 g/dL. Cancer 2005. © 2005 American Cancer Society. [source]

Complex of urokinase-type plasminogen activator with its type 1 inhibitor predicts poor outcome in 576 patients with lymph node,negative breast carcinoma

CANCER, Issue 3 2004
Peggy Manders M.Sc.
Abstract BACKGROUND The ability of a solid tumor to grow and metastasize has a significant dependence on protease systems, such as the plasminogen activation system. The plasminogen activation system includes the urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1), among other molecules. Both uPA and PAI-1 are established prognostic factors for patients with breast carcinoma. In the current study, the authors investigated whether the complex of uPA with PAI-1 is also associated with the natural course of this malignancy. METHODS Cytosolic levels of uPA, PAI-1, and the uPA:PAI-1 complex were measured in tumor tissue from 576 patients with lymph node,negative invasive breast carcinoma using quantitative enzyme-linked immunosorbent assays. Patients did not receive adjuvant systemic therapy, and the median follow-up duration was 61 months (range, 2,187 months) after primary diagnosis. Correlations with well known clinicopathologic factors were assessed, and univariate and multivariate survival analyses were performed. RESULTS uPA:PAI-1 complex levels were positively associated with adverse histologic grade and inversely correlated with estrogen and progesterone receptor status. On univariate analysis, increased levels of the uPA:PAI-1 complex were found to be associated with reduced recurrence-free survival (RFS) and overall survival (OS) rates. On multivariate analysis, uPA:PAI-1 complex levels were found to be an independent predictor of OS (P = 0.039), but not RFS (P = 0.240). When uPA and PAI-1 levels were not included in the multivariate analysis, uPA:PAI-1 complex levels became a significant predictor of both RFS and OS (P = 0.029 and P = 0.007, respectively). CONCLUSIONS The results of the current study demonstrate that uPA:PAI-1 complex levels have prognostic value on univariate analysis. In addition, increased uPA:PAI-1 complex levels were significantly associated with poor OS on multivariate analysis. Increased uPA:PAI-1 complex levels were also significantly associated with reduced RFS rates after the exclusion of uPA and PAI-1 levels from the multivariate analysis model. Cancer 2004. © 2004 American Cancer Society. [source]

Cyclooxygenase-2 in oligodendroglial neoplasms

CANCER, Issue 7 2003
Elias A. Castilla M.D.
Abstract BACKGROUND Although increased expression of cyclooxygenase-2 (COX-2) has been described in association with a variety of neoplasms, including tumors of astrocytic derivation, limited data are available on COX-2 expression in oligodendrogliomas. METHODS The current study retrospectively reviewed 53 oligodendrogliomas and 7 oligodendroglioma-predominant oligoastrocytomas (mixed gliomas) for COX-2 expression and MIB-1 proliferative index (by immunohistochemistry) and for chromosome 1p status (by fluorescence in situ hybridization). RESULTS Patients included 35 males and 25 females, with a mean age of 41 years (range, 12,73 years) at the time of surgery. Forty-four tumor specimens were classified as World Health Organization (WHO) Grade II neoplasms and 16 as WHO Grade III tumors. MIB-1 labeling indices (marker of cell proliferation) ranged from 0 to 22.3 (mean 4.5). Twenty-eight tumor specimens demonstrated allelic loss on chromosome 1p. Positive staining was observed in 17 tumor specimens with COX-2 antibody. COX-2,positive tumor specimens were also evaluated with CD68 (macrophage/microglial cell marker) by coimmunolabeling to confirm that the observed COX-2 immunostaining was not due to immunoreactive macrophages or microglial cells. COX-2 expression, lack of allelic loss at chromosome 1p, and high proliferation indices were associated with decreased survival (P = 0.002, P = 0.009, and P = 0.015, respectively). No correlation with outcome was found with patient gender, age at diagnosis, or histologic grade. CONCLUSIONS Chromosome 1p, COX-2 immunoreactivity, and MIB-1 labeling indices correlated with outcome and were associated with decreased survival. There was not a one-to-one correspondence between COX-2 immunoreactivity and lack of allelic loss at chromosome 1p. Tumors with expression of COX-2 by immunohistochemistry may, in theory, benefit from treatment with therapeutic agents that inhibit COX-2. Cancer 2003;98:1465,72. © 2003 American Cancer Society. DOI 10.1002/cncr.11632 [source]

Histologic grade, stage, and survival in breast carcinoma,,

Myoid differentiation and prognosis in adult pleomorphic sarcomas of the extremity

CANCER, Issue 4 2003
An analysis of 92 cases
Abstract BACKGROUND The results of a recent study demonstrated an association between myoid differentiation and an adverse prognosis in adult patients with pleomorphic sarcoma, as determined by 5-year metastasis-free survival rates. METHODS To confirm the importance of muscle differentiation on prognosis in a well controlled clinical context, 92 samples from patients with pleomorphic sarcoma of the extremity from a single institution were immunostained with 4 monoclonal antibodies believed to be correlated with myoid differentiation: ,-smooth muscle actin, muscle-specific actin, desmin, and myoglobin. RESULTS Forty-two cases were positive for at least 1 muscle marker and 50 cases were uniformly negative. Between the two groups, there was no significant difference in tumor size, tumor extent, or patient age found; however, histologic grade was significantly higher (P = 0.038) in the myoid tumors. The 5-year survival differed significantly between patients with myoid tumors (35%) and those without myoid tumors (65%) (P = 0.0054). Myoid differentiation remained an adverse prognostic indicator after adjusting for clinically significant factors (i.e., histologic grade, tumor size, tumor extent, and patient age) (P = 0.01) (hazard ratio, 2.39; 95% confidence interval, 1.24,4.63). Furthermore, there was an inverse relation found between the number of myoid markers present and survival (P = 0.004). CONCLUSIONS Myoid differentiation was found to be an independent indicator of adverse prognosis in adult patients with pleomorphic spindle cell sarcoma of the extremity. Cancer 2003;98:805,13. © 2003 American Cancer Society. DOI 10.1002/cncr.11617 [source]

Low expression of p27Kip1 is associated with tumor size and poor prognosis in patients with renal cell carcinoma,

CANCER, Issue 4 2002
Toshiro Migita M.D.
Abstract BACKGROUND Proliferative activity in tumors depends on regulation of the cell cycle. p27Kip1 (p27) plays a pivotal role as a negative regulator of the cell cycle. A decrease in p27 expression has been reported in many kinds of tumors, but little is known regarding p27 in patients with renal cell carcinoma (RCC). METHODS Expression of p27 and the related cyclins (cyclin A, cyclin E, and cyclin D1) was examined immunohistochemically in 67 patients with of clear cell RCC. The Ki-67 labeling index (MIB-1 LI) and clinicopathologic parameters related to a poor prognosis also were analyzed. To determine their prognostic significance, univariate and multivariate survival analyses were performed. RESULTS In tumors, there was considerable immunoreactivity for cyclin A, cyclin D1, and MIB-1, and the mean values for each were 1.08%, 16.1%, and 1.5%, respectively. Cyclin E expression was rare. The expression of p27 was correlated strongly with the expression of cyclin A (correlation coefficient, 0.432; P < 0.0004) and cyclin D1 (correlation coefficient, 0.476; P < 0.0004). Also, an inverse correlation was present between p27 expression and tumor size (P = 0.0377). In univariate analysis, the unfavorable prognostic factors were high TNM stage (P < 0.0001), large tumor size (P = 0.0016), high histologic grade (P = 0.0104), and low p27 expression (P < 0.0001). In multivariate analysis, high TNM stage (P = 0.0035) and low p27 expression (P = 0.0235) were independent prognostic factors for disease specific survival in patients with RCC. CONCLUSIONS The results of this study suggest that low p27 expression may be a significant and independent, unfavorable prognostic factor in patients with renal cell carcinoma. Cancer 2002;94:973,9. © 2002 American Cancer Society. DOI 10.1002/cncr.10338 [source]

Early experience with two-dose daclizumab in the prevention of acute rejection in cardiac transplantation

CLINICAL TRANSPLANTATION, Issue 5 2004
Dominique Joyal
Abstract:, Background:, Daclizumab is a human monoclonal antibody that binds to the interleukin-2 receptor. It has been used as induction therapy in heart transplantation with repeated administrations over several weeks. At our institution, we use a two-dose regimen of daclizumab based on its extended half-life. We sought to determine the incidence of acute rejection with 2-dose daclizumab in cardiac transplantation. Methods:, Eighteen consecutive heart transplants performed at a single center were analyzed retrospectively. Patients received daclizumab (2 mg/kg) within 8 h of cardiac transplantation and a second dose (1 mg/kg) 2 wk thereafter. Maintenance immunosupression included mycophenolate mofetil, prednisone and either cyclosporine or tacrolimus, based on side-effect profile. The endpoint was the incidence of acute rejection as defined by a histologic grade >2 according to the classification of the International Society of Heart and Lung Transplantation. Results:, Four patients had acute rejections (all were 3A) during the first 3 months post-transplantation. All four patients had rejection at the first biopsy and only two had rejection thereafter. None of the rejections were hemodynamically significant and no patients were hospitalized. All except one rejection was seen in the context of low 2-h cyclosporine levels. The two-dose regimen was easier to administer on an outpatient basis and resulted in lower cost. Conclusions:, This preliminary report suggests that induction therapy with a two-dose regimen of daclizumab appears to be safe and well tolerated in patients undergoing cardiac transplantation. [source]

Immunohistologic study on the expressions of ,-fetoprotein and protein induced by vitamin K absence or antagonist II in surgically resected small hepatocellular carcinoma

HEPATOLOGY, Issue 6 2001
Miwako Fujioka
Sixty-eight cases of single hepatocellular carcinoma (HCC) with less than 3 cm of diameter were immunohistochemically examined for the expressions of ,-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II). In cancerous tissues, the expression rate was significantly higher for PIVKA-II (34 cases [50%]) than AFP (21 cases [31%]) (P < .05), suggesting a higher specificity of PIVKA-II to small HCC. Sixteen of the 68 cases (24%) were positive to both AFP and PIVKA-II, and in 8 of the 16 cases, AFP and PIVKA-II expressing areas within a nodule were clearly divided by a fibrous septum. According to histologic grades, PIVKA-II expression was confirmed in 2 of the 15 well-differentiated HCCs, and in the well-differentiated component of 6 of the 12 "nodule-in-nodule",type well-differentiated HCCs. AFP expression was not found in well-differentiated HCCs, but found in 16 of the 40 moderately differentiated HCCs (40%) and in the moderately differentiated component of 3 of the 12 "nodule-in-nodule",type well-differentiated HCCs. The positive rate in the tissues was correlated to the serum levels for both AFP and PIVKA-II. In addition, frequency of tissue,PIVKA-II expression was higher than tissue-AFP expression in the cases whose serum protein level was within the normal range. This indicates that AFP and PIVKA-II have different patterns of tissue expression and of secretion to the blood. In comparison with tissue-AFP,negative cases, tissue-AFP,positive HCCs had a larger tumor size, higher frequencies of portal vein invasion and intrahepatic metastasis, a high Ki-67 labeling index, and a lower rate of recurrence-free survival. Thus, tissue-AFP,positive HCCs are suggested to be biologically more malignant than those HCCs that are AFP-negative and PIVKA-II,positive. [source]

An in vivo model of degenerative disc disease

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2003
Jason P. Norcross
Although the precise etiology of low back pain is disputed, degeneration of the intervertebral disc is believed to play an important role. Many animal models have been described which reproduce the changes found in degenerative disc disease, but none allow for efficient, large-scale testing of purported therapeutic agents. The purpose of this study was to develop a simple animal model resembling degenerative disc disease using the intervertebral discs found in the tails of rats. The proximal two intervertebral discs in the tails of 20 rats were injected with either chondroitinase ABC or control (phosphate buffered saline, PBS). The tails were harvested at 2 weeks, and measurements were made of intervertebral disc height (measured radiographically and histologically), biomechanics (stiffness, hysteresis, and residual deformation), and histologic appearance. Treatment with chondroitinase ABC resulted in a significant loss in intervertebral disc height (radiographic intervertebral disc height, p < 0.001; histologic intervertebral disc height, p < 0.001) and significant increases in all biomechanical parameters (stiffness, p < 0.001; hysteresis, p < 0.006; residual deformation, p < 0.004) compared to PBS controls. Intervertebral discs treated with chondroitinase ABC had significantly lower histologic grades for each grading category (nucleus pulposus (NP), annulus fibrosus, and proteoglycan staining) compared to controls. The results of injury with chondroitinase ABC were similar to the findings in degenerative disc disease: reduced intervertebral disc height, diminished proteoglycan content, loss of NP cells, and increased stiffness of the disc. Thus, the model appears to be a reasonable tool for the preliminary in vivo evaluation of proposed treatments for degenerative disc disease. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]

Methylation-Associated Silencing of Death-Associated Protein Kinase Gene in Laryngeal Squamous Cell Cancer,

THE LARYNGOSCOPE, Issue 8 2005
Wei-Jia Kong MD
Abstract Objectives/Hypothesis: Death-associated protein kinase (DAPK) is a Ca2+/calmodulin-regulated Ser/Thr kinase that functions as a positive mediator of programmed cell death. It has been found that DAPK gene is frequently inactivated by its promoter hypermethylation in some cancers and tumor cell lines. However, it is not clear whether promoter hypermethylation of DAPK gene exists in laryngeal squamous cell cancer (LSCC). The aim of this study was to investigate the promoter methylation status of the DAPK gene in LSCC and the effect of 5-Aza-2'-deoxycytidine (5-Aza-CdR), a demethylating agent, on Hep-2 cells, a human laryngeal cancer cell line, and on xenografts of Hep-2. Methods: Methylation-specific polymerase chain reaction (PCR) and reverse-transcription PCR techniques were used to determine the promoter methylation status and mRNA expression of DAPK gene in LSCC. Furthermore, Hep-2 cells in vitro and in vivo were treated by 5-Aza-CdR to explore the effect of demethylating agents on DAPK mRNA expression and tumor growth. Results: Hypermethylation of DAPK gene promoter was found in 39 (67.2%) of 58 LSCC samples. There was no significant difference in the promoter hypermethylation rate among the samples of different histologic grades or samples from patients with different T stages. However, there was significant difference in methylation status of DAPK gene between the samples from patients in N0 stages and those from patients in N1 stages. No promoter hypermethylation of DAPK gene was found in any of the five normal laryngeal tissue samples. DAPK mRNA expression was not detected in tumor specimens with promoter hypermethylation. On the contrary, DAPK mRNA expression was observed in the unmethylated tumor specimens, specimens from tissues adjacent to the tumor, and normal laryngeal tissues samples. Promoter hypermethylation of DAPK gene was found, and no DAPK mRNA expression was detected in Hep-2 cells. DAPK mRNA expression in Hep-2 cells and xenografts could be restored by treating cells and xenografts with 5-Aza-CdR. The tumors' xenografts, induced by way of Hep-2 cell injection in nude mice treated with 5-Aza-CdR, were obviously smaller than those in nude mice treated with phosphate-buffered saline. Conclusions: Abnormal loss of DAPK expression could be associated with aberrant promoter region methylation in the LSCC. 5-Aza-CdR may slow the growth of Hep-2 cells in vitro and in vivo by reactivating tumor suppressor gene DAPK silenced by de novo methylation. [source]

How much does Gleason grade of follow-up biopsy differ from that of initial biopsy in untreated, Gleason score 4,7, clinically localized prostate cancer?