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)

The class I tyrosine kinase growth-factor receptors include epidermal growth factor receptor (EGFR), ErbB2 (c-erbB-2, HER-2/neu), ErbB3 and ErbB4. To elucidate their role in the regulation of homeostasis and carcinogenesis, we examined the expression of the receptors in normal urothelium and in urothelial carcinoma by immunohistochemistry. EGFR was expressed in the basal cells of normal urothelium, while ErbB2, ErbB3 and ErbB4 were present mainly in the superficial layer. A distinct reciprocal distribution was observed between the EGFR and the remaining members of the subclass (P = 0.0001). Both BCL-2 protein and Ki-67 antigen (MIB-1) showed a strong positive association with EGFR (P = 0.002) and an inverse correlation with ErbB2, ErbB3 or ErbB4 (P = 0.0004, 0.0000, and 0.001, respectively). With regard to carcinoma, there was no important relationship between receptor overexpression and tumour grading (P > 0.1), while only EGFR overexpression was correlated with muscular invasion (P = 0.02). Coexpression of EGFR-ErbB3 and ErbB3-ErbB4 was more often detected in high-grade tumours and correlated with the extent of tumour invasion. Our data indicate that class I receptors are differentially expressed in normal urothelium in vivo, but an orchestrated expression pattern does not exist during tumorigenesis.
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PMID:Expression patterns of erbB receptor family in normal urothelium and transitional cell carcinoma. An immunohistochemical study. 923 Sep 11

Angiogenesis is essential for tumour growth and metastasis. In spite of its relevant biological significance, recent studies have produced conflicting results regarding the capacity of microvessel quantifications in breast carcinomas to predict patients' outcome and the existence of metastasis. In order to provide further information in this issue, we evaluated tumour angiogenesis in a series of 45 primary breast carcinomas (mean age: 55.3 +/- 14.2) and examined their association with established or potentially useful prognostic parameters. Microvessels were highlighted by immunohistochemical staining for factor VIII-related antigen and counted in the three most vascularized areas in a 200 x field (0.74 mm2) by four observers simultaneously. Results were analysed for the average vessel count of each case. The mean intratumoural microvessel count was 57.7 +/- 24.4 (range: 24.3 to 127.7). We found a statistically significant association between angiogenesis and age. The microvessels count in patients younger than 50 years was 67.8 +/- 26.4, from 51 to 70 years, 52.0 +/- 22.8 and over 71 years, 46.1 +/- 14.2 (p = 0.03). Node positive patients had slightly higher microvessel counts (60.3 +/- 25.3) than node negative ones (54.4 +/- 23.5); this difference was not significant (p = 0.42), even when we considered each age group per se. No association was found between angiogenesis and tumour size, histologic grade, estrogen receptor, MIB-1 index, ploidy and expression of p53 and c-erbB-2. Our results suggest that invasive breast carcinoma-induced angiogenesis is age-dependent.
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PMID:Angiogenesis in breast cancer is related to age but not to other prognostic parameters. 925 52

The aim of the study was to correlate the DNA Index (DI) and S-phase fraction (SPF) values determined by multiparametric flow cytometry in breast cancer (mainly T1 and T2 stages) with several clinico-pathologic variables and other biological parameters. For this purpose, a total of 136 breast cancers were submitted to flow cytometry and to several types of immunohistochemical analyses. Among clinico-pathologic data we considered pT, pN and grade and among immunohistochemical markers, hormonal receptors, P53, c-erbB-2 and MIB-1. We found that DNA aneuploidy was strongly correlated with high tumoral grade, absence of hormonal receptors, high proliferation, as shown by high MIB-1 (> or = 36%) and SPF values (> or = 13.3%), and P53 positivity. Grouping the tumours according to their DI values, we observed a relative significantly higher correlation of the near-triploid range carcinomas (DI 1.40-1.60) with immunohistochemical expression of P53 (p = 0.0001). Near-triploid DI was also associated with a high proliferative activity, expressed both by SPF (p = 0.0001) and MIB-1 reactivity (p = 0.0001), high tumoral grade (p = 0.0001) and presence of axillary metastases (p = 0.03). These data suggest that DNA near-triploid tumours in breast cancer may have a more aggressive behaviour in comparison with other DI classes.
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PMID:Cytometric DNA analysis and prognostic biomarkers in breast carcinoma. Expression of P53 product in the different ploidy classes. 937 11

To document whether c-erbB-2 over-expression or p53 accumulation in tumour cells was predictive of response to chemo- or radiotherapy, we analyzed a population of patients with breast cancer assigned to neo-adjuvant therapy (median follow-up: 54 months). T2/T3-N0N1b-M0 tumours (329 cases) were treated either by FAC chemotherapy or by radiotherapy before surgery, and the clinical response was classified as complete or incomplete. Expression of c-erbB-2 and p53 was retrospectively evaluated by immunohistochemistry. Proliferation rate was assessed by means of MIB-1 antibody and by S-phase fraction. A complete response to chemotherapy was observed in 38/167 patients (23%). Complete response rate was 20% in c-erbB-2-negative tumours, and rose to 31% in tumours with c-erbB-2 over-expression, but this trend was not statistically significant. There was no correlation between p53 staining and response to treatment, whereas chemosensitivity was found correlated with histological grade and S-phase. A complete response to radiotherapy was observed in 64 of the 156 evaluable patients (41%). Complete response rate was 41% in c-erbB-2- or p53-negative tumours, 54% in tumours with c-erb-B-2 over-expression, and 44% in tumours with p53 accumulation. There was no correlation between response to radiotherapy and histological grade or proliferative rate. No prognostic value was found for c-erbB-2 or p53 expression, whereas the 5-year survival rate was 85% for patients presenting a tumour with a low proliferating index (MIB-1 < 10%), and 68% for patients presenting a tumour with a high proliferative index. In multivariate analysis, node status (RR = 2), MIB-1 immunostaining (RR = 2), and tumour size (RR = 1.8) were found to be associated with survival. These results indicate that c-erbB-2 or p53 expression is not significantly associated with tumour response to neo-adjuvant chemo/radiotherapy in our series of breast cancers.
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PMID:No significant predictive value of c-erbB-2 or p53 expression regarding sensitivity to primary chemotherapy or radiotherapy in breast cancer. 949 54

We examined whether the cell proliferation index by MIB-1, HER-2/neu gene amplification, Gleason grade, and pretreatment level of serum prostate specific antigen (PSA) correlated with postradiation recurrence (PRR) in patients with prostatic adenocarcinoma. Formalin-fixed, paraffin-embedded tissue sections from 42 pretreated cases of prostatic adenocarcinoma (38 needle biopsy and 4 transurethral resection specimens) were immunostained for MIB-1 (MMI, Ventana Medical Systems, Tucson, Ariz). HER-2/neu gene amplification was analyzed by fluorescence in situ hybridization using the Oncor unique sequence probe (Oncor, Gaithersburg, Md). The cell proliferation index by MIB-1 was determined by labeling index; levels of HER-2/neu were analyzed semiquantitatively. Twenty-three of 42 patients (55%) were considered to have PRR on the basis of consecutive elevations of serum levels of PSA to greater than 1.5 ng/mL after completion of treatment (mean follow-up time, 33.4 months). The cell proliferation index correlated with PRR on both univariate and multivariate analyses. Of the 23 tumors that showed PRR, 18 (78%) revealed a high cell proliferation index, compared with 6 of 19 cases (32%) that showed no PRR. Twelve of 23 cases of prostatic adenocarcinoma (52%) in the recurrent group showed HER-2/neu gene amplification, compared with 5 of 19 (26%) in the nonrecurrent group; these findings reached near significance on univariate analysis. Pretreatment levels of serum PSA also reached significance on multivariate analysis. In this preliminary study, the cell proliferation index by MIB-1 reached independent significance in predicting PRR in patients with prostatic adenocarcinoma, whereas HER-2/neu amplification by fluorescence in situ hybridization reached near significance.
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PMID:Cell proliferation rate by MIB-1 immunohistochemistry predicts postradiation recurrence in prostatic adenocarcinomas. 958 87

Fifty-nine paraffin-embedded astrocytic gliomas (four WHO grade 1, 21 WHO grade 2, 17 WHO grade 3 and 17 glioblastomas, WHO grade 4) were immunohistochemically investigated for expression of transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGF-R) and oncoprotein c-erbB-2 by semiquantitative assessment. Proliferative activity was simultaneously analyzed by using the antibody Ki-67 (MIB-1). Immunostaining in neoplastic cells was quantified by image analysis. Concerning the antibodies used, the percentage of immunoreactive cells increased with histologic malignancy. There was no expression of EGF-R and c-erbB-2 in the majority of low-grade astrocytomas. However, small focal expressions of TGF-alpha and EGF-R were observed in several low-grade astrocytomas (11/25), suggesting an early stimulation of malignant transformation. With regard to percentage, a strong positive correlation between TGF-alpha and EGF-R-stained cells was found, indicating an autocrine stimulation of the mitogenic pathway of the TGF-alpha/EGF-R system. Likewise, indices of EGF-R and c-erbB-2 positive cells correlated significantly. Less significant correlations were also seen between EGF-R, c-erbB-2 frequencies and the Ki-67 labeling index. However, there was no correlation between TGF-alpha and Ki-67 indices. The results suggest that TGF-alpha expression is not directly related to the proliferative potential as judged by the Ki-67 labeling index. Furthermore, besides EGF-R and c-erbB-2, other growth factors and their receptors or mutant EGF-R might participate in the proliferative activity of gliomas.
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PMID:Correlation of TGF-alpha and EGF-receptor expression with proliferative activity in human astrocytic gliomas. 958 31

Controversy continues regarding the prognostic utility of detection of p53 gene abnormalities in node-negative breast cancer. To resolve this, we used a rapid and nonisotopic PCR-single strand conformation polymorphism method to screen for mutations in exons 4-8 of the p53 gene in primary tumors from 422 node-negative breast cancer patients. The prevalence of p53 mutation in the exons tested was 18%. p53 mutation was significantly associated with several markers of poor prognosis including larger tumor size, high tumor grade, low hormone receptor content, increased expression of MIB-1 (Ki-67), amplification of the HER-2/neu oncogene, and accumulation of the p53 protein. After a median duration follow-up period of 74 months, the parameters of tumor diameter > or =20 mm, HER-2/neu oncogene amplification, and p53 mutation were found to be associated with a statistically significant shortened duration of disease-free and overall survival, but not the parameters of tumor grade, hormone receptor levels, or p53 expression. The poor prognosis associated with p53 mutation was observed primarily in patients with a tumor diameter of > or =20 mm. In multivariate analysis, p53 mutation was a risk factor for increased risk of recurrence and death from breast cancer independent of tumor size, hormone receptor levels, HER-2/neu amplification, and MIB-1 expression. We conclude that a relatively simple and rapid single strand conformation polymorphism method of determining p53 mutation status in node-negative breast cancers can provide independent prognostic information.
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PMID:Analysis of p53 gene mutation by polymerase chain reaction-single strand conformation polymorphism provides independent prognostic information in node-negative breast cancer. 967 32

Conventional histopathological criteria based on light microscopy are used in pulmonary oncologic pathology in order to establish the diagnosis of tumor, but most frequently they are insufficient, accurate diagnosis requiring ultrastructural and immunohistochemical investigations. The method of immunostaining allowed some molecular marker to be evaluated. Some of them seem to be important in carcinogenesis as a general process, while others have high specificity for lung tumors. Estimation of EGFR and c-erbB-2 protein immunoreactivity showed a significantly stronger staining with NSCLC and was correlated to the poor differentiation of the tumors, undergoing an aggressive biological behavior and an unfavorable prognosis. The expression of p53 protein was found in 19 cases by immunostaining with DO-7 antibody. Immunotracing of more than 50% of the tumoral cells was a predictive factor for the progression of the disease. The growing rate of tumoral proliferative activity was evaluated by immunotracing technique (MIB-1), allowing the Ki-67 index of labeling to be calculated.
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PMID:Immunohistochemical markers in the morphological diagnosis of lung carcinoma. 974 20

The aim of this study is to investigate the predictive value of proliferative activity assessment and E-cadherin expression by means of immunohistochemistry in identifying patients with laryngeal squamous cell carcinoma at a high risk for occult node metastasis. Thirty consecutive patients treated for laryngeal carcinoma with false clinically negative nodes (occult metastases, pN+) between the years 1980 and 1990 were selected for this study. A group of 30 cases with negative cervical lymph nodes (pN-) having a similar anatomic site and tumor size distribution was used as control. In each case, several histological parameters, including grade, pattern of invasion, number of mitosis (x10 high-power field), tumor inflammatory infiltrate, and tumor sclerosis, were assessed. Proliferative activity was determined using immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and MIB-1. Other putative prognostic factors investigated at the immunohistochemical level were the cell adhesion molecule E-cadherin and two oncoproteins, p53 and c-erbB-2. In pN+ cases, the expression of PCNA and MIB-1 was significantly higher than in the pN- group. Moreover, a significant loss of E-cadherin expression was observed in carcinomas with occult metastases. No differences in p53 and c-erbB-2 oncoproteins were found between pN+ and pN- cases. Among the other pathological parameters examined, only histological grade was significantly associated with the presence of occult metastases, but on multivariate analysis, this relationship was lost. We conclude that PCNA, MIB-1, and E-cadherin are independent predictors of occult nodal disease in laryngeal squamous cell carcinoma, and their immunohistochemical determination could be useful in identifying patients with clinically negative lymph nodes who are at considerable risk for occult metastases and who may benefit from elective neck dissection.
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PMID:Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination. 981 33

Because of histological similarities between nephrogenic adenomas and clear cell adenocarcinomas of the urinary tract, there is the potential for diagnostic confusion between these two entities. The histopathologic features of 13 nephrogenic adenomas and five clear cell adenocarcinomas of the urethra and urinary bladder are compared in this report, and detailed immunohistochemical staining profiles are provided for these tumors. Only 2 of the 13 nephrogenic adenomas contained clear cells, and these constituted less than 10% of the lesions. In contrast, four of the five clear cell adenocarcinomas contained prominent areas with clear cells. Nephrogenic adenomas generally showed only mild cytologic atypia, whereas four of the five clear cell adenocarcinomas showed severe atypia. A single mitotic figure was identified in only two of the nephrogenic adenomas, whereas the mitotic rate in the clear cell adenocarcinomas ranged from 2 to 14 per 10 high-power fields. None of the nephrogenic adenomas showed evidence of necrosis, but focal necrosis was noted in four of the five clear cell adenocarcinomas. In general, the nephrogenic adenomas and clear cell adenocarcinomas showed negative to weak staining with CK903 but strong staining with AE1, AE3, and Cam 5.2. Variable staining was observed with Brst-3 and antibodies to S-100, CEA (monoclonal and polyclonal), LeuM-1, and CA19.9. Nephrogenic adenomas and clear cell adenocarcinomas were all negative for prostate-specific acid phosphatase (PSAP), prostate-specific antigen (PSA), and estrogen and progesterone receptors (except for two nephrogenic adenomas, which showed only focal weak staining for estrogen receptor). Neither bcl-2 nor c-erbB-2 staining was able to discriminate between the tumors. However, strong staining for p53 was noted in each clear cell adenocarcinoma and in none of the nephrogenic adenomas. MIB-1 positivity in nephrogenic adenomas ranged from 0 to 13 (average of 5.5) per 200 cells, whereas the positive range for clear cell adenocarcinomas was 33 to 70 (average of 47) per 200 cells. In summary, histopathologic features that favor clear cell adenocarcinoma over nephrogenic adenoma include a predominance of clear cells, severe cytological atypia, high mitotic rate, necrosis, high MIB-1 positivity, and strong staining for p53.
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PMID:Clear cell adenocarcinoma and nephrogenic adenoma of the urethra and urinary bladder: a histopathologic and immunohistochemical comparison. 986 32


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