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)

Our aim was to compare the occurrence and prognostic significance over 14-20 years of immunocytochemically detected S100A4 and other tumour variables in primary tumours from 349 patients with operable breast cancer. For a cut-off of 1% staining of the malignant cells, the antibody to S100A4 stains positively 56% of the carcinomas. There was a significant association of staining for S100A4 with tumours fixed to the chest wall, staining for c-erbB-2, c-erbB-3, pS2, cathepsin D and, inversely, at borderline levels with staining for estrogen receptor. Using Wilcoxon statistics in univariate analyses, staining for S100A4, nodal status, tumour class, histological grade and staining for c-erbB-2, p53 were associated negatively and staining for estrogen receptor, progesterone receptor were associated positively with patient survival times. The survival times of patients with S100A4-negative carcinomas with or without one of the other tumour variables showed no significant differences, whilst those of patients with S100A4-positive carcinomas showed significant differences in a negative or a positive way. Multivariate regression analysis for 137 patients showed that staining for S100A4 is most highly correlated with patient deaths, but involved lymph nodes, fixed tumours, high histological grade and staining for progesterone receptor were also significant independent prognostic variables. Our results suggest that in this set of patients, the tumour variable most tightly correlated with patient death is S100A4.
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PMID:Comparison of the metastasis-inducing protein S100A4 (p9ka) with other prognostic markers in human breast cancer. 1075

The c-erbB-2 proto-oncogene encodes a transmembrane protein tyrosine kinase receptor of 185 kDa (p185) and has been associated with several types of human cancers. In human breast cancer, overexpression of p185 occurs in 15-30% of cases, correlates with poor prognostic factors and characterizes breast cancers with a more aggressive behavior. Overexpression of p185 is usually associated with c-erbB-2 amplification, though it may occur independently and thus define subpopulations of breast cancers which might be of clinical interest. p185 expression is usually detected by immunohistochemistry (IHC) and few studies have been carried out to evaluate the p185 content of breast cancers with an ELISA technique. In this context, we showed, in 106 breast cancer samples, that p185 was expressed at high levels in 13.2%, intermediate levels in 55.7% and negative ones in 31.1% of cases. All p185 positive samples showed a c-erbB-2 oncogene amplification while none of the p185 negative samples and only 4% of p185 imtermediate samples had an amplification of c-erbB-2. p185 expression is significantly correlated with the negativity of estrogen and progestrone receptors, with high levels of cathepsin D and in some conditions with axillary nodal involvement. Thus, using the p185 ELISA assay, the c-erbB-2 status of breast cancers can be defined and moreover a subset can be discriminated which is characterized by intermediate levels of p185 and absence of c-erbB-2 amplification. The quantitative approach towards p185 in breast cancers affords the possibility of identifying more appropriately patients with high or low risk and thus permits adaptation of therapeutic regimens.
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PMID:Relevance of p185 HER-2/neu oncoprotein quantification in human primary breast carcinoma. 1109 92

The aim of the study was to identify variables that may predict the response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer as maturing data from the literature indicate that this therapeutic strategy might be beneficial to some but harmful to others. Clinico-pathologic variables including age, histology, tumor differentiation, as well as immunohistochemical overexpression of p53, mdm2, c-erbB-2, and cathepsin D in 37 of these patients were evaluated as possible predictors of response to the NACT. Fifty-five patients with stage IIB cervical cancer submitted to two courses of cisplatin/ifosfamide/mesna prior to definitive treatment with radical surgery or radiation therapy were the subjects of this study. The clinical response rate was 80% but none of the variables was able to predict response to NACT. Unless methods are found enabling us to predict response and therefore to identify those patients that could benefit from including NACT in the treatment of locally advanced cervical cancer, only women with primarily resectable tumors should be selected for this multimodality approach as a result of the possibility of cross-resistance with radiation therapy in nonresponders.
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PMID:Predicting response to neoadjuvant chemotherapy in patients with cervical carcinoma: can we do without any longer? 1124 Jun 65

Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and inhibitor, plasminogen activator-type 1 (PAI-1) are proposed to be of prognostic significance in some cancers. To determine the prognostic value of the urokinase plasminogen activation system in ovarian cancer, levels of uPA, uPAR, and PAI-1 were measured in extracts of ovarian cancer tissue using ELISA tests. uPA and PAI-1 were determined in 70 tumor extracts and uPAR in 43 extracts. Levels were correlated with age, tumor histology, stage, grade, lymph node and metastatic status, residual disease, risk of recurrence, epidermal growth factor receptor (EGFR) expression, cathepsin D (Cath-D), and c-erbB-2 levels. uPA and uPAR did not exhibit correlation with any of these parameters. However, patients with high grade tumor, recurrence, and lower EGFR and Cath-D had significantly higher PAI-1 levels compared to those of others (P < 0.05). Kaplan-Meier plots of survival were compared. uPA and uPAR were not related to disease-free or overall survival. Although low PAI-1 appeared to predict a longer overall survival, the difference was not statistically significant. Multivariate analysis revealed that PAI-1 was a predictor for overall survival although it was not as strong as stage. These results suggest that elevated PAI-1 seems to be correlated with an unfavorable prognosis in ovarian cancer.
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PMID:Clinical relevance of urokinase-type plasminogen activator, its receptor and inhibitor type 1 in ovarian cancer. 1124 Jul 1

The objective of this study was to evaluate the value of platelet count, p53, MDM2, c-erbB-2, and cathepsin D immunoreactivity as predictors of lymph node metastasis (LNM) as well as their prognostic significance in patients with stage IB cervical cancer treated by radical hysterectomy between 1991 through 1995. We also report on the outcome of a protocol considering lymph-vascular space invasion (LVSI) in addition to LNM as a strong motivation for adjuvant radiotherapy. A total of 93 patients were the subject of this retrospective study. The incidence of positive nodes was high (30.1%). Thrombocytosis (>/= 400.000/mm3) was present in 6.7% of patients. Positive immunostaining was found for p53 (50.6%), MDM2 (21.7%), c-erbB-2 (14.5%), and cathepsin D (45.8%), but none of them was able to predict LNM. Only thrombocytosis was associated with an unfavorable prognosis: a statistically significant association was shown with relapse-free and overall survival in an univariate analysis (P = 0.0431 and P = 0.0012, respectively) with a tendency to significance in multivariate analysis (P = 0.079 and P = 0.0882, respectively). We postulate that thrombocytosis in early stage cervical cancer could be a marker for subclinical tumor burden. LVSI, regarded as an indication for adjuvant radiotherapy, was no longer associated with poor relapse-free or overall survival, but resulted in a 41% postoperative irradiation rate. Further research is needed to establish the value of LVSI in postoperative radiotherapy decision making.
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PMID:The prognostic significance of p53, mdm2, c-erbB-2, cathepsin D, and thrombocytosis in stage IB cervical cancer treated by primary radical hysterectomy. 1124 Jul 67

Some node-negative breast cancer patients, with initially good prognosis, relapse from their cancer and are poorly identified. In the present study, based on prospective data of 197 tumors, we measured cathepsin D (cath D, n=197), pS2 protein (n=125), c-erbB-2 oncoprotein (n=100) and epidermal growth factor receptor (EGF-R, n=99) to better define the risk of relapse of node-negative patients in comparison with that defined by the clinical and histological factors. The median follow-up in surviving patients was 75 months. Univariate analysis indicated that patients with histological grade III tumors (the Scarff, Bloom and Richardson classification) had a much poorer prognosis than those with histological grade I or II tumors (P=0.0027 for relapse-free survival and P=0.0156 for overall survival). When the population of node-negative patients was divided by tertiles, high cath D levels showed a significant association with an early relapse (P=0.0316). Using cut-off values, patients with high cath D (> or =25 pmol/mg protein) or c-erbB-2 oncoprotein (> or =4 Human Neu Unit/microg protein) levels, had a significant worse relapse-free survival (P=0.0147 and 0.0417, respectively). No prognostic information was supported by pS2 protein or EGF-R measurements. In multivariate analysis, histological grade, cath D and c-erbB-2 oncoprotein remained independent predictors of recurrence (P=0.005, 0.0361 and 0.0321, respectively). By combining low levels of cath D and c-erbB-2 oncoprotein in histological grade I or II tumors, we identified a subgroup of patients with a 100% relapse-free survival probability at 6 years of follow-up. Moreover, the subgroup of patients with histological grade I or II tumors and high values of both cath D and c-erbB-2 oncoprotein showed a prognosis as poor as the subgroup defined by histological grade III alone, respectively 66% and 70% relapse-free survival at 6 years of follow-up. In conclusion, the combination of conventional prognostic factor (histological grade) and biochemical factors (cath D and c-erbB-2 oncoprotein) enabled us to identify, in this preliminary study, a subgroup of patients having an increased risk of relapse in a group (node-negative patients with low histological grade tumors) considered as good prognosis.
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PMID:Prognostic impact of cathepsin D and c-erbB-2 oncoprotein in a subgroup of node-negative breast cancer patients with low histological grade tumors. 1125 Nov 76

Inflammatory breast carcinoma (IBC) is a rare but aggressive form of breast cancer. In this first-ever study, we investigated the role of nine prognostic markers' expression (estrogen receptor [ER], progesterone receptor [PR], p53, C-erbB-2, epidermal growth factor receptor [EGFR], cathepsin D [CD], proliferating cell nuclear antigen [PCNA], DNA ploidy, and S-phase fraction [SPF]) and disease outcome in IBC cases compared with the control group. A case control study of IBC was conducted on 40 test cases with two controls per case matching age, grade, and number of axillary lymph nodes sampled. During 7 years of this study, 10% of all patients with breast cancer had IBC. In this study, 84% of IBC cases showed positive axillary lymph nodes compared with 63% in control group. The expression of nine prognostic markers, that is, ER, PR, p53, C-erbB-2, EGFR, CD, PCNA, SPF, and DNA ploidy, was studied by immunohistochemistry and flow cytometry. Hormone receptor status showed an inverse correlation (p < 0.05). Among p53, C-erbB-2, EGFR, and CD in the IBC group, only p53 showed a significant correlation, with 70% positivity in IBC versus 48% positivity in the control group (p < 0.05). Much higher SPF and PCNA positivity was seen in the IBC group compared with the control group (p < 0.05). DNA ploidy also showed a significant correlation compared with the control group (p < 0.05). After a median follow up of 18 months, median overall survival in the IBC group was 1.8 years (range 0.6-5.8 years) compared with 3.0 years (range 2.5-7.0 years), with a p value of 0.0001.
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PMID:Case control study of prognostic markers and disease outcome in inflammatory carcinoma breast: a unique clinical experience. 1184 51

Endometrial adenocarcinoma is the most common malignant neoplasm of the female genital tract and, despite its relative frequency, the molecular events that contribute to the development and progression of the lesion remain poorly understood. The normal human endometrium is characterized by hormone-dependent variations during the menstrual cycle. This tightly controlled system is disturbed in endometrial hyperplasia and carcinomas and a series of changes initiate and promote progression towards the malignant phenotype. These changes can be subdivided into discrete steps, involving activation of oncogenes, inactivation of tumour suppressor genes, deregulation of cell cycle regulators or other proteins involved in tumour invasion and progression. Immunohistochemical expression of different biomarkers such as hormone receptor status (ER, PR), proliferation associated indices (PCNA, MIB1), oncogene (c-erbB-2), tumour suppressor gene products (pRb, p53 protein), cell cycle related proteins (cyclin D1, cyclin E, p21/WAF1), anti-apoptotic protein (bcl-2), adhesion molecule (CD44s), proteolytic enzyme (cathepsin D), heat shock protein (hsp27) and metallothionein (MT) has shown the contribution of these molecules to endometrial carcinogenesis in a hormone-dependent or independent manner as an early or late event. In addition, these biomarkers seem to be correlated with tumour differentiation or myometrial invasion, and therefore could be considered as indicators of the biological behaviour of endometrial carcinoma. Furthermore, the interrelationships of these molecular markers show that these genetic dysregulations could be implicated in the control of cell proliferation and differentiation, and thereby in the multistep process of endometrial carcinogenesis.
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PMID:Immunohistochemical tumour markers in endometrial carcinoma. 1612 80

One of prognostic factors known as Nottingham Prognostic Index (NPI), which is combination of known prognostic factors such as tumor size, grade and axillary node status, is recently in usage in some European countries in clinical practice in prediction of breast carcinoma patients' survival. Therefore, the aim of this study was to verify, according to our experience, the prognostic significance of Nottingham Prognostic Index (NPI) in breast carcinoma patients in association with other new prognostic factors. In this study 148 consecutive specimens of breast carcinoma patients were analyzed. The following data for each patient were collected: age, tumor size, histological grade, axillary lymph node status, overall survival, estrogen (ER), progesterone (PR) receptor expression as well as expression of bcl-2, Ki-67, nm23, HER-2/neu, and p53. The Nottingham Prognostic Index (NPI) was calculated from the pathological information and patients were grouped according to the standard NPI index into: good prognostic group (GPG), moderate prognostic group (MPG), and poor prognostic group (PPG). The correlation of prognostic groups according to the NPI with other prognostic and predictive factors such as age, ER, PR, p53, bcl-2, Ki-67, nm23, Ki-67, Cathepsin D and HER-2/neu on overall survival was analyzed. The results of univariate analysis showed statistically significant correlation between patients' age, NPI prognostic groups and stage of disease with patients survival. When other prognostic factors were correlated with NPI prognostic groups there was not additional prognostic discrimination in given prognostic groups. Only marginally statistically significant influence of p53 expression was found on patient survival between MPG and PPG. It seems that other prognostic factors in combination with NPI prognostic groups do not have in our group of patients practical clinical relevance for the management of patients with breast carcinoma.
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PMID:[The value of searching for additional prognostic factors in combination with Nottingham Prognostic Index in breast carcinoma patients]. 1614 66

The aim of our study was to evaluate the association between the mammographic appearance and the biologic characteristics of high-grade breast carcinomas. Three hundred and twenty patients with breast carcinomas were studied. Histological examination showed 83 (26%) high-grade ductal carcinomas. Immunohistochemistry was carried out by using antibodies against estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, p53 and cathepsin D. In 60/83 high-grade carcinomas we studied the mammographic appearance. Asymmetric density with poorly defined margins without microcalcifications was the major mammographic finding in 49/60 (approximately 82%) high-grade ductal carcinomas. HER-2/neu positivity (68.7%) and p53 positivity (48.2%) were statistically correlated with asymmetric density with poorly defined margins without microcalcifications in high-grade carcinomas. We observed loss of ER and PR receptors in 50%, whereas loss of PR receptors was observed in 65% of high-grade breast carcinomas. Cathepsin D (> 20%) was detected in 38.5% of high-grade carcinomas. Our findings suggest a significant relationship between mammographic appearance and biologic markers in high-grade breast carcinomas.
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PMID:Correlation of mammographic appearance and molecular prognostic factors in high-grade breast carcinomas. 1655 Sep 66


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