Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

No reliable pathologic criteria have been identified that predict clinical behavior in adrenal and extra-adrenal pheochromocytomas (PHEOs). Reliable prognostic markers for the prediction of clinical outcome are needed to assign optimal treatment for potentially malignant tumors. In this report, we evaluated several molecular markers (topoisomerase II alpha, E-cadherin, HER-2/neu, and retinoblastoma (RB) gene protein) that have not been previously studied in PHEOs. Paraffin-embedded, formalin-fixed tissue blocks from 50 cases of PHEO (30 benign and 20 malignant, 31 adrenal and 19 extra-adrenal) were obtained from University of Utah Health Sciences Center, Salt Lake City, and the Medical College of Wisconsin, Milwaukee. Gross (tumor size, weight, local extension, cyst formation, hemorrhage, necrosis), microscopic (pleomorphism, hyaline globules, intranuclear inclusion, mitotic count, capsular and vascular invasion, ganglionic/neuronal differentiation), and immunohistochemical features (topoisomerase II alpha, p53, MIB-1, E-cadherin, RB, and HER-2/neu) were studied. With the exception of vascular invasion (P = 0.025), there were no unequivocal gross or microscopic characteristics that distinguished benign from malignant lesions (P approximately = 0.11-0.71). Topoisomerase III and MIB-1 indices in malignant lesions were significantly higher than those observed in benign lesions (P = 0.012 and 0.019). Differences in p53 expression were not statistically significant (P = 0.082). Loss in RB protein product expression was significantly more common in malignant lesions (P = 0.001), E-cadherin loss and HER-2/-neu overexpression were not observed in any of the benign or malignant lesions. We studied the immunohistochemical expression of topoisomerase II alpha, MIB-1, p53, RB gene protein product, E-cadherin, and HER-2/neu in a series of adrenal and extra-adrenal PHEOs. Overexpression of topoisomerase II alpha and MIB-1 and loss of RB protein product were more common in malignant lesions, whereas p53, E-cadherin, and HER-2/neu do not seem to have diagnostic utility in the prediction of biologic behavior in these neoplasms.
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PMID:Prognostic value of immunohistochemical expression of topoisomerase alpha II, MIB-1, p53, E-cadherin, retinoblastoma gene protein product, and HER-2/neu in adrenal and extra-adrenal pheochromocytomas. 1112 18

Recurrent respiratory papillomatosis (RRP) has a juvenile aggressive form and an adult more indolent form. Most cases of RRP are cytologically benign; however, some undergo malignant transformation. At present, there are no known markers that help identify patients at risk for aggressive disease. We investigated by immunohistochemistry expressions of topoisomerase alpha II, MIB-1, p53, p21, E-cadherin, retinoblastoma (RB) gene protein product, HER-2/neu, and steroid hormone receptors in a case of juvenile respiratory papillomatosis with malignant transformation to determine whether these markers are associated with malignant transformation. Histologic examination of the pulmonary lobectomy specimen revealed well-differentiated squamous carcinoma and invasive papillomatosis. Increased staining was found in areas of invasive papillomatosis for topoisomerase alpha II, p53, and MIB-1, with highest labeling indices in areas of squamous carcinoma. Staining intensity for RB gene protein product showed gradual decline from benign papilloma (3+) and invasive papillomatosis (2+) to squamous carcinoma (0-1+). Expression of p21 was similar in benign papilloma and invasive papillomatosis but showed reduction in squamous carcinoma. Expressions of E-cadherin, HER-2/neu, and steroid hormone receptors did not appear to correlate with biologic behavior. Increased topoisomerase alpha II and p53 expression along with reduced RB gene protein product and p21 expression may serve as markers of transformation to invasive papillomatosis and squamous carcinoma.
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PMID:Topoisomerase alpha II, retinoblastoma gene product, and p53: potential relationships with aggressive behavior and malignant transformation in recurrent respiratory papillomatosis. 1127 21

Our objective was to investigate the prognostic significance of cell turnover (apoptosis and proliferation) in breast cancer patients. Apoptosis was microscopically quantitated on histological sections from 791 breast cancer patients with long-term follow-up (median, 16.3 years). Apoptotic counts were also compared with proliferation data (mitotic counts and MIB-1 labeling); apoptosis data derived from terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay; and pathobiological variables, including p53, erbB-2, and estrogen receptor (ER). High apoptotic counts were associated with increased cellular proliferation, ER negativity, immunopositivity of erbB-2 and p53 (P < 0.0001), and shortened disease-specific survival (DSS; P = 0.0009) and disease-free survival (DFS; P = 0.0006). Other factors associated with shortened DFS and DSS by univariate analysis were high tumor grade, nodal metastases, and large tumor size (P < 0.0001 for each). Multivariate analysis of data for all of the patients demonstrated that tumor size, nodal status, ER, histological grade, and erbB-2 showed independent prognostic value. In node-negative patients, tumor size and mitotic rate per 1000 cells independently predicted DFS (P = 0.0055). Tumor grade was the only independent predictor of DSS. For node-positive patients, tumor size, nodal status, ER, and erbB-2 were independent prognostic factors. The number of mitoses per 1000 was independently associated with DFS (P = 0.043) but not with DSS. Apoptosis data did not provide independent prognostic value in any, node-positive or node-negative, breast cancer patients.
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PMID:Measures of cell turnover (proliferation and apoptosis) and their association with survival in breast cancer. 1141 May 11

Pathologic factors of predictive value for carcinoma ex pleomorphic adenoma (CXPA), an aggressive salivary gland malignancy, are poorly defined. Because residual mixed tumor may be relatively inconspicuous and various carcinoma subtypes are encountered, misdiagnosis is common. To describe the pathologic features and identify potential prognostic factors, we retrospectively examined 73 cases of CXPA of the major salivary glands treated at Mayo Clinic. Paraffin section immunostaining for keratins (AE1/AE3, CK7, CK20), epithelial membrane antigen, carcinoembryonic antigen, vimentin, actin, S-100 protein, glial fibrillary acidic protein, and p53 and c-erbB-2 oncoproteins was performed in 69 cases. DNA content and proliferation indices were determined by digital image analysis of Feulgen- and MIB-I-stained sections, retrospectively. Survival was calculated by the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The carcinoma component was predominant in 82% of tumors. Adenocarcinoma not otherwise specified (31 cases) and salivary duct carcinoma (24 cases) were the most frequent histologic subtypes. Sixty-two tumors were high grade (Broders 3 or 4). Residual mixed tumor was extensively hyalinized in 54 cases. Pathologic features significantly associated with overall survival included pathologic stage (P =.009), tumor size (P =.012), grade (P =.005), proportion of carcinoma (P =.004), extent of invasion (P =.002), and proliferation index of carcinoma (P =.03). Of 4 patients with intracapsular (noninvasive) carcinoma, none had an adverse outcome. The immunohistochemical profile of CXPA included positive staining reactions in the malignant component for AE1/AE3 in 97% of cases, CK7 in 94%, epithelial membrane antigen in 86%, carcinoembryonic antigen in 75%, vimentin in 52%, and S-100 protein in 29%. Expression of p53 and c-erbB-2 oncoproteins was detected in 41% and 30% of the carcinomas, respectively, but neither was associated with decreased survival. High-grade salivary adenocarcinoma that is difficult to classify should raise the suspicion of possible CXPA. Intracapsular carcinoma has a benign clinical course. Significant prognostic factors in CXPA include tumor stage, grade, proportion of carcinoma, extent of invasion, and proliferation index.
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PMID:Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. 1143 14

We report here a case of a patient affected by endometrial cancer and treated primarily with leuprolide, the surgical approach being unfeasible due to her compromised conditions. The therapy was continued for more than 6 years, and no progression of the disease was observed. During this period, some histological and immunohistochemical evaluations of the tumour (morphology, grading, proliferation and apoptotic index, E-cadherin expression) were performed. Furthermore, the expression of m-RNA for luteinizing-hormone releasing hormone (LHRH) receptors was determined. The results showed a discrepancy between some biological parameters of the tumour and its clinical characteristics. In fact, despite features suggestive of a progression of the cancer (such as the increase of both tumour grading and proliferating capacity (MIB-1), and a fall in the reparative process (appearance of mutated p53, reduced expression of both bcl-2 and c-erb-2) being detected, neither local invasion nor metastatic lesions were clinically observed. This discrepancy might be due to the maintenance of high levels of E-cadhezin. Moreover, since this tumour was shown to express mRNA for LHRH receptors, new evidence is provided about the favourable impact of LHRH analogue treatment in patients affected by endometrial cancer.
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PMID:Longstanding survival without cancer progression in a patient affected by endometrial carcinoma treated primarily with leuprolide. 1148 60

Prediction of biologic behavior in adrenocortical neoplasms is difficult because of the lack of availability of reliable clinical, biochemical, and pathologic prognostic markers. Reliable objective markers predictive of clinical outcome in adrenocortical neoplasms are needed to assign optimal treatment of potentially malignant tumors. In the current article, the authors evaluated a set of molecular markers (topoisomerase II alpha (Topo II alpha), MIB-1, p53, human epithelial cadherin (E-cadherin), retinoblastoma gene protein product, and HER-2/neu) and correlated their expression with histologic diagnosis and clinical outcome. Paraffin-embedded, formalin-fixed tissue blocks from 30 cases of adrenocortical neoplasms (15 benign and 15 malignant) were obtained from the surgical pathology archives at the University of Utah Health Sciences Center (Salt Lake City, UT) and the Medical College of Wisconsin (Milwaukee, WI). Age, gender, recurrence, tumor size and weight, hemorrhage, necrosis, pleomorphism, mitotic count, capsular and lymphovascular invasion, hyaline globules, intranuclear inclusions, and immunohistochemical expression of Topo II alpha, p53, MIB-1, E-cadherin, retinoblastoma gene protein product, and HER-2/neu were studied. Clinical data were obtained from the clinical charts, or communication with the treating physician, or both. Adrenocortical neoplasms with hemorrhage, necrosis, large size (>5 cm), weight more than 100 g, nuclear pleomorphism, lymphovascular invasion, and brisk mitotic rate (more than 5 per 30 high-power fields) were more likely to behave in a malignant fashion (P approximately 0.001-0.009). The difference in proliferation indices in benign and malignant neoplasms was statistically significant (P < 0.001). The difference in p53 staining in benign and malignant neoplasms also was statistically significant (P < 0.001). Higher p53 labeling index (>20%) was present in 73% (11/15) of malignant lesions but was found in only 1 of 15 (6.6%) benign lesions. The difference in retinoblastoma staining between benign and malignant neoplasms was statistically significant (P = 0.004). There was no significant difference in staining pattern of E-cadherin expression between benign and malignant lesions. HER-2/neu overexpression was not observed in any of the benign or malignant adrenocortical neoplasms.
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PMID:Value of topoisomerase II alpha, MIB-1, p53, E-cadherin, retinoblastoma gene protein product, and HER-2/neu immunohistochemical expression for the prediction of biologic behavior in adrenocortical neoplasms. 1155 48

Programmed cell death (apoptosis) may play a role in tumor development and progression. The importance of apoptosis dysregulations in ductal carcinoma in situ (DCIS) and its relationships with p53 mutations and expression of bcl-2 has received little attention in the literature. In a series of 58 DCIS patients, we evaluated the number of apoptotic cells by the TUNEL technique in subgroups of DCIS and correlated it with immunohistochemical expression of hormone receptors, c-erbB-2, p53, bcl-2, and Ki-67 (MIB-1) and DNA content measured by image cytometry. High apoptotic index (greater than 3%) was related to high tumor grade, negative hormone receptors, c-erbB-2 overexpression, aneuploidy and lack of bcl-2 immunohistochemical stain. Apoptosis was not related to p53 or proliferative index. The findings are similar to those found in infiltrating breast cancer.
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PMID:Apoptosis in ductal carcinoma in situ of the breast. 1167 2

We investigated the expression of oncogenes p53, c-erbB-2, and bcl-2 and cell proliferative activity in 62 newly diagnosed superficial pTa papillary bladder tumors. Based on the 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) and 1999 WHO classifications, 19 were urothelial neoplasias of low malignant potential (LMP) and 43 low-grade (grade 1) papillary carcinomas. All the patients underwent transurethral resection and were followed up to 97 months; 42 had recurrences. Initial biopsies were tested for p53, c-erbB-2, and bcl-2 proteins using DO7, CB11, and bcl-2 124 monoclonal antibodies. Cell proliferation was assessed by MIB-1 mAb and mitotic count. LMP had significantly lower MIB-1 (p = 0.002) and p53 immunopositivity (p = 0.03), mitotic count (p = 0.006), and recurrence rates (p = 0.04) than did grade 1 cases, whereas no difference was observed for c-erbB-2 and bcl-2 expression. The median disease-free survival for LMP was 76 months but only 15 months for grade 1 cases (p = 0.002). Although the cohort is small, the results indicate that the distinction between LMP and low-grade (grade 1) papillary urothelial neoplasias, as proposed by the 1998 WHO/ISUP and 1999 WHO classifications, reflects different biologic activity and clinical behavior; however, a long-term follow-up is advisable also for patients with LMP.
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PMID:Biologic differences between noninvasive papillary urothelial neoplasms of low malignant potential and low-grade (grade 1) papillary carcinomas of the bladder. 1171 43

We have identified two novel polymorphisms in the prostate-specific antigen (PSA) gene promoter regions, the A-AA allele and G-A allele. Furthermore, we have found that A-AA occurred frequently in tumors with higher PSA expressions. We hypothesize that allelic differences may be associated with different phenotypes of breast cancer. To test this hypothesis, we assayed the PSA genotype for 101 breast cancer cases. We also performed immunostaining analysis for estrogen receptor, p53, MIB-1 and c-erbB-2 on all the tumors. At the time of diagnosis, the A-AA allele occurred more frequently in the tumors characterized by small tumor size, good to moderate differentiation, p53-negativity and low tumor proliferation activity. Our results suggest that the presence of the A-AA allele at the PSA promoter region is associated with less aggressive forms of breast cancer and could be looked on as a favorable prognostic factor.
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PMID:Correlation of prostate-specific antigen promoter polymorphisms with clinicopathological characteristics in breast cancer. 1216 76

The expression of p53, c-erbB-2, bcl-2 and c-myc proteins was compared to the quantity of the nucleolar organiser regions (AgNORs) and MIB-1 antigen to elucidate the relationship between oncogene expression and rapidity of cell proliferation and tumor growth fraction. Sections from 50 male breast carcinomas (MBC) and 62 superficial papillary bladder neoplasias were stained with the standardised AgNOR method and monoclonal antibodies MIB-1, DO7, CB11, bcl-2 124 and 9E11. p53 immunopositivity was associated with high AgNOR quantity and MIB-1 scores both in MBC and bladder neoplasm. c-erbB-2 expression was associated with high AgNOR quantity in bladder neoplasm. bcl-2 expression was associated with low AgNOR quantity in MBC. c-myc expression was associated with high AgNOR quantity in MBC. MBC patients with low AgNOR quantity, and p53, c-erbB-2 and c-myc immunonegativity had the longest overall survival. Patients with bladder neoplasia with low AgNOR quantity, negative p53 and positive c-erbB-2 immunostaining had the longest disease-free survival time. Our results indicate that p53 overexpression reflects both the rapidity of cell proliferation, as assessed by AgNOR quantity, and tumor growth fraction, as assessed by MIB-1 scores, while c-erbB-2, c-myc and bcl-2 expression mainly reflects the rapidity of cell proliferation. The combination of AgNOR quantity and oncogene expression may stratify patients into different risk groups.
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PMID:Relationship between AgNORs, MIB-1 and oncogene expression in male breast carcinoma and papillary superficial bladder neoplasm. 1288 2


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