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)

Tumor angiogenic activity is an important process linked to tumor growth, metastasis, and invasion. In the present study we investigated whether intratumoral microvessel density (MVD), as assessed with immunohistochemistry, is of prognostic relevance in a series of 77 breast cancer patients with node-negative disease. The mean MVD in the hot spots ranged from 9 to 106 (median 31) vessels per x200 optical field. Patients were grouped into 3 categories of low (27 pts), medium (26 pts), and high (24 pts) MVD. Angiogenesis was not related to the primary tumor dimensions (T-stage) or the histology differentiation. An inverse association of MVD with estrogen receptor (ER) expression was noted (p=0.0007), while high MVD was directly related to c-erbB-2 overexpression (p=0.04) and high MIB1 proliferation index (p=0.02). In univariate and multivariate analysis of relapse-free survival, MVD was the only variable significantly and independently linked to relapse. It is concluded that high intratumoral angiogenic activity is linked with early relapse in node-negative breast cancer.
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PMID:Angiogenesis relates to estrogen receptor negativity, c-erbB-2 overexpression and early relapse in node-negative ductal carcinoma of the breast. 1259 15

Conservatively treated premenopausal breast cancer has a higher rate of local relapse as well as an increased genetic predisposition to cancer. The current study's purpose was to evaluate the interactions between BRCA-1/2 status and molecular biologic markers in a cohort of conservatively managed breast cancer patients. Seventy-six premenopausal women treated with breast-conserving surgery and radiation therapy were this study's focus. All patients were treated with wide local excision with or without axillary dissection, followed by radiation to the intact breast. Systemic therapy was administered as clinically indicated. All patients in this study had an available paraffin block from the primary tumor and agreed to undergo complete sequencing of the BRCA-1 and BRCA-2 genes. The primary breast tumor tissue from each patient was immunohistochemically stained for estrogen receptor (ER), progesterone receptor (PR), p53, HER-2/neu, and Proliferating Cell Nuclear Antigen (PCNA). Of the 76 patients tested for BRCA, 50 patients had wild-type BRCA-1 and BRCA-2, 15 had variants of unclear significance, 6 had deleterious mutations in BRCA-1, and 5 had deleterious mutations in BRCA-2. p53 positivity correlated with deleterious mutations in BRCA-1 (p = 0.023), but not in BRCA-2. Though not significant, there was a trend for ER and PR negativity to correlate with BRCA-1 mutation (p = 0.087 and 0.054, respectively); there were no correlations between ER, PR, and BRCA-2. Though not significant, all 11 tumors with BRCA mutations were HER-2/neu negative. Patients with BRCA mutations have a unique molecular profile. These data can be helpful in understanding differences in the biologic behavior of patients with familial breast cancers.
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PMID:BRCA status, molecular markers, and clinical variables in early, conservatively managed breast cancer. 1275 24

Immunohistochemical study of expression of nm 23 and c-erbB-2 protein markers in primary tumor and metastases of colorectal adenocarcinoma showed that the incidence and expression of both protein markers in primary tumor tissue tended to increase after the appearance of liver metastases. Peculiarities of protein expression in tumor metastases in lymph nodes and liver and the possibility of using these markers as additional prognostic criteria in colorectal cancer are discussed.
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PMID:Immunohistological study of NM 23 and C-erbB-2 expression in primary tumor and metastases of colorectal adenocarcinoma. 1291 Feb 92

The purpose of this study was to explore differences in erbB-2 alterations in recurrent or metastatic disease, as compared with the primary tumor. Primary invasive breast cancers and subsequent local, regional, or distant metastases from 113 patients were examined. Primary and all metastatic or recurrent tumors were evaluated for erbB-2 expression using immunohistochemistry (with CB11, TAB 250, DAKO anti-erbB-2, HercepTest) and fluorescence in situ hybridization. Immunohistochemical data derived from the 4 reagents on the same tumor sample were highly correlated (pair-wise correlation range, 78-90%). Immunohistochemical and fluorescence in situ hybridization erbB-2 data were also generally concordant (average agreement, 82%; range, 75-87%). Approximately 80% of the primary and recurrent or metastatic tissues from the same patient had similar patterns of erbB-2 protein expression and gene copy number, although in approximately 20%, disagreement was observed. Discordant cases were mostly erbB-2 normal primary tumors with altered metastases, although the opposite pattern was also observed. Interestingly, erbB-2 discordance, based on CB11 data, was associated with subsequent survival, whereas there were no similar associations with other erbB-2 stains. In approximately 80% of patients, erbB-2 protein expression and gene copy number were similar in the primary tumor and locally recurrent or distant metastases. The lack of complete concordance suggests clonal selection or genetic drift in some cases.
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PMID:erbB-2 (HER-2) and breast cancer progression. 1296 47

Occult disseminated tumor cells are the major cause of relapse in patients with primary operable breast cancer but detection and characterization of these few cells is difficult. Applying immunohistochemistry, an immunomagnetic enrichment technique (IET) and immunocytochemistry (IC), we studied 58 breast cancer patients without overt metastases for the frequency of cytokeratin-positive (CK+) bone marrow (BM) cells coexpressing the epithelial adhesion molecule 17-1A (EpCAM) and c-erbB-2 and analyzed the primary tumor for these antigens as a strategy for additional immunotherapy. The primary tumors were analyzed for the target antigens by a pathologist. Dissemination of CK+ cells was studied in 4-6 x 10(6) BM cells by IC alone. For characterization of CK+ cells, 10-15 x 10(6) BM cells were incubated with microbeads coupled to antibodies detecting the target antigens, labelled cells were separated on selection columns and the positively (BM cells carrying the target antigen) and negatively (BM cells without target antigen) selected fractions were stained for CK+ cells. The effectiveness of these methods was confirmed in cell culture models. 17-1A was detected in all primary tumors and c-erbB-2 overexpression (2+, 3+) was found in 25/58 tissue samples. In total, analyzing 15-20 x 10(6) BM cells in each patient, the detection rate for CK+ cells in the BM was 69% (40/58 patients). Interestingly, analysis of the positive and negative enrichment fractions showed that the 17-1A antigen was coexpressed on CK+ cells in only 6 patients and c-erbB-2/CK+ cells were found in only one patient. Although 17-1A and c-erbB-2 were frequently detected in the primary tumor, these antigens were rarely expressed on CK+ BM cells. Whether the applied IET is not able to detect low amounts of these target antigens has to be clarified. Nevertheless, applying cell-cycle independent protocols in clinical trials requires careful elucidation of those patients who might benefit from these therapies.
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PMID:Rare expression of target antigens for immunotherapy on disseminated tumor cells in breast cancer patients without overt metastases. 1461 76

BACKGROUND: HER-2/neu and c-kit (CD117) onco-protein are increasingly being recognized as targets for therapy in solid tumors, but data on their role in malignant melanoma is currently limited. We studied the prevalence of overexpression of HER-2/neu and c-Kit in 202 patients with malignant melanoma to evaluate a possible prognostic value of these molecular targets in malignant melanoma. METHODS: Overexpression of HER-2/neu and c-Kit was evaluated using immunohistochemical assays in 202 archival tissue specimens. RESULTS: Between 1991 and 2001, 202 subjects (109 males; 54% and 93 females; 46%) with malignant melanoma were studied with a mean age of 57 years (age range: 15-101 years). The most common histologic type was amelanotic melanoma (n = 62; 30.7%) followed by superficial spreading melanoma (n = 54; 26.7%). The depth of penetration of melanoma (Breslow thickness, pT Stage) ranged from 0.4 mm (stage pT1) to 8.0 mm (stage pT4A). Mean thickness was 2.6 mm (stage pT3A). The ECOG performance scores ranged from 0 to 3. Only 2 patients (0.9%) revealed HER-2/neu overexpression, whereas 46 (22.8%) revealed c-Kit overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit positive and negative groups (p = 0.36). Interestingly, not only was c-Kit more likely to be overexpressed in the superficial spreading type, a preliminary association between the presence or absence of c-Kit overexpression and the existence of another second primary tumor was also observed. CONCLUSIONS: The results of our large study indicate that the HER-2/neu onco-protein neither has a role in melanogenesis nor is a potential target for clinical trials with monoclonal antibody therapy. This indicates there is no role for its testing in patients with malignant melanoma. Although c-Kit, expressed preferentially in the superficial spreading type, may not have prognostic value, it does have significant therapeutic implications as a molecular target warranting further investigation.
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PMID:Immunohistochemical determination of HER-2/neu overexpression in malignant melanoma reveals no prognostic value, while c-Kit (CD117) overexpression exhibits potential therapeutic implications. 1461 73

We examined the prognostic value of c-erbB-2, p53, bcl-2 and bax overexpression in breast cancer. Immunostaining for c-erbB-2, p53, bcl-2 and bax gene expression was performed on 121 paraffin-embedded specimens of Stage I, II and III breast cancer patients diagnosed and treated in Hippokration Hospital, Athens Medical School, between 1986 and 1992. The primary tumor from 27 (24.1%), 69 (59%), 18 (15%) and 63 (53.4%) patients stained positively for c-erbB-2, p53, bcl-2 and bax gene expression, respectively. Significant correlations were found between bax overexpression and age (P=0.04), tumor size (P=0.02) and disease stage (P=0.001), while no other significant associations were found between other molecular markers and clinical or histological parameters. None of the individual molecular markers examined proved to be independent prognostic factor for patients with breast carcinoma. C-erbB-2, p53, bcl-2 and bax genes have limited prognostic value. An approach that combines several molecular markers with established clinicopathological criteria may help physicians make more accurate predictions of prognosis in patients with breast cancer.
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PMID:Molecular markers in breast cancer: can we use c-erbB-2, p53, bcl-2 and bax gene expression as prognostic factors? 1496 83

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 < or =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.
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PMID:Occult metastases in axillary lymph nodes as a predictor of survival in node-negative breast carcinoma with long-term follow-up. 1512 40

HER-2/neu oncoprotein is overexpressed in a variety of human tumors and is associated with malignant transformation and aggressive disease. Due to its overexpression in tumor cells and because it has been shown to be immunogenic, this protein represents an excellent target for T-cell immunotherapy. Peptide extracts derived from primary HLA-A*0201-positive (+) HER-2/neu+ human tumors by acid elution (acid cell extracts (ACEs)) were tested for their capacity to elicit in HLA-A*0201 transgenic mice, cytotoxic T lymphocytes (CTLs) lysing HLA-A*0201+ HER-2/neu+ tumor cells. Injections of ACE in transgenic mice induced CTLs capable of specifically lysing HER-2/neu+ tumor cell lines (also including the original HER-2/neu+ primary tumor cells from which the ACEs were derived) in an HLA-A*0201-restricted fashion. Adoptive transfer of ACE-induced CTLs was sufficient to significantly prolong survival of SCID mice inoculated with HLA-A*0201+ HER-2/ neu+ human tumor cell lines. Cytotoxicity of such ACE-induced CTL lines was directed, at least as detected herein, also against the HER-2/ neu peptides HER-2 (9(369)) and HER-2 (9(435)) demonstrating the immunodominance of these epitopes. HER-2 peptide-specific CTLs generated in the HLA-A*0201-transgenic mice, upon peptide immunization, lysed in vitro HER-2/neu+ human tumor cell lines in an HLA-A*0201-restricted manner and, when adoptively transferred, conferred sufficient protection in SCID mice inoculated with the same human tumor cell lines as above. However, CTLs induced by ACEs displayed enhanced efficacy in the therapy of xenografted SCID mice compared with the HER-2 peptide-specific CTLs (i.e., HER-2 [9(369)] or HER-2 [9(435)]). Even by administering mixtures of CTLs specific for each of these peptides, the prolongation of survival achieved was still inferior compared with that obtained with ACE-induced CTLs. This suggested that additional epitopes may contribute to the immunogenicity of such tumor-derived ACEs. Thus, immunization with ACEs from HER-2/neu+ primary tumor cells appears to be an effective approach to generate multiple and potent CTL-mediated immune responses against HER-2/neu+ tumors expressing the appropriate HLA allele(s). By screening ACE-induced CTL lines with synthetic peptides encompassing the HER-2/neu sequence, it is feasible to identify immunodominant epitopes which may be used in mixtures as vaccines with enhanced efficacy in both the prevention and therapy of HER-2/neu+ malignancies.
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PMID:Generation of human tumor-specific CTLs in HLA-A2.1-transgenic mice using unfractionated peptides from eluates of human primary breast and ovarian tumors. 1516 33

The major limiting factor in the successful application of adjuvant therapy for metastatic disease is the lack of adjuvant specificity that leads to severe side effects. Reasoning that T cells of the immune system are highly specific, we generated tumor-specific T cells by genetic modification of mouse primary T cells with a chimeric receptor reactive with the human breast cancer-associated Ag erbB-2. These T cells killed breast cancer cells and secreted IFN-gamma in an Ag-specific manner in vitro. We investigated their use against metastatic breast cancer in mice in an adjuvant setting, and compared their effectiveness with the commonly applied adjuvants doxorubicin, 5-fluorouracil, and herceptin. Mice were inoculated orthotopically with the human erbB-2-expressing spontaneously metastatic mouse breast cancer 4T1.2 in mammary tissue, and the primary tumor was surgically removed 8 days later. Significant metastatic disease was demonstrated in lung and liver at the time of surgery on day 8 with increased tumor burden at later time points. T cell adjuvant treatment of day 8 metastatic disease resulted in dramatic increases in survival of mice, and this survival was significantly greater than that afforded by either doxorubicin, 5-fluorouracil, or herceptin.
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PMID:Gene-engineered T cells as a superior adjuvant therapy for metastatic cancer. 1526 51


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