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 authors report on two gonadotropic carcinomas of the adenohypophysis that occurred in a55-year-old man (Case 1) and a 53-year-old woman (Case 2), with signs of mass effect and amenorrhea, respectively. Both lesions were macroadenomas. The tumor in Case 1 metastasized to dura mater, skull, nasal sinus, and larynx 2 years after patient presentation, whereas that in Case 2 spread to vertebral bodies and ribs after a 19-year latency. Histologically, the primary, recurrent, and metastatic lesions in Case 1 featured brisk mitotic activity and high MIB-1 levels as well as p53 labeling indices. Immunoreactivity for HER-2/neu was assessable only in rare neoplastic cells of the second recurrence and in 80% of cells of the dural metastasis. Low-level HER-2/neu gene amplification was evident in the recurrent tumors and metastasis. The sellar and metastatic tumors in Case 2 resembled benign gonadotropic adenoma with oncocytic change; p53 accumulation, HER-2/neu overexpression, and HER-2/neu gene amplification were not present. The results indicate that low-level amplification of the HER-2/neu gene might be associated with pituitary carcinomas in which more aggressive behavior is seen. Further studies are needed to determine whether HER-2/neu plays a role in the pathogenesis of pituitary carcinoma.
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PMID:Gonadotropic pituitary carcinoma: HER-2/neu expression and gene amplification. Report of two cases. 1292 17

A case-cohort study was designed to correlate various histopathologic and molecular variables with distant failure in endometrial cancer by analyzing phenotypic and molecular indices in hysterectomy specimens. From an overall population of 283 patients with endometrial cancer, we selected a cohort including all 49 patients who experienced any recurrence and 76 randomly chosen patients without recurrence. Expression of nuclear proliferating cell nuclear antigen (PCNA), MIB-1 (a marker of cell proliferation), and p53 was determined with digital image analysis, and cell membrane HER-2/neu and bcl-2 were quantitated visually. Ploidy and DNA indices were determined with flow cytometry. Overall, 6 immunohistochemical and 11 flow cytometric cases were eliminated because of technical inadequacies. Distant failures were defined as primary recurrences that developed outside the pelvis or vagina. Median follow-up was 91 months. Distant failures occurred in 13% of the patients. Cervical stromal invasion, positive adnexae, myometrial invasion >50%, positive lymph nodes, positive peritoneal cytology, lymphovascular invasion, grade 3 histology, nonendometrioid subtype, p53 >33%, strong HER-2/neu membranous staining, aneuploidy, S-phase fraction > or =9%, proliferative index > or =14%, and DNA index > or =1.5 significantly (P<0.05) predicted distant failures. However, a logistic regression model identified only p53 (OR=43.73; P<0.005), lymphovascular invasion (OR=11.59; P<0.001), and cervical stromal invasion (OR=11.29; P=0.001) as cogent predictors of distant failures. Only 3% of patients without any of these three predictors developed distant failures compared with 36% of those with at least one of the three (P<0.01). Thus, locoregional therapy may be insufficient when at least one of these predictors is present.
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PMID:Molecular and histopathologic predictors of distant failure in endometrial cancer. 1464 51

The use of predictive factors allows a more effective use of available therapies by enabling clinicians to distinguish patients likely to obtain substantial benefit from treatment from those for whom the same therapy is less likely to be effective. A most relevant aspect of clinical research is thus to develop alternative therapeutic approaches which are more efficacious for this latter group, particularly important since treatment effects are likely to be small. In the preoperative setting several predictors of response were identified. They include: diameter of the lesion (larger lesions respond less than smaller lesions), MIB-1 increased expression associated with increased response to chemotherapy, and estrogen receptor (ER) and progesterone receptor (PgR) expression in the tumor typically associated with increased response to endocrine therapies. Other factors include HER-2/neu overexpression, which is a target for treatment with the humanized monoclonal antibody against its extracellular domain, is hypothesized to increase response to anthracycline combination chemotherapy and to lead to an improved response to some endocrine agents (e.g. letrozole) rather than to others. Although primary endocrine therapy demonstrated activity and low profile of side effects in selected populations of older patients, it is infrequently used. On the other hand, chemotherapy remains the mainstay of treatment being considered to be a more active and better documented option. Experience at the European Institute of Oncology on 399 patients with large or locally advanced breast cancer (cT2-T4, N0-2, M0) treated with primary chemotherapy, indicated that a proper selection of primary treatment should be based on tumor characteristics such as ER and PgR status. In particular, patients with tumors with no ER and PgR expression (endocrine-unresponsive disease) at the baseline core-biopsy had a significantly higher response rate to chemotherapy if compared with tumors with some ER/PgR expression. In fact, the absence of ER and PgR expression was the strongest predictors of pCR at the multivariate analysis (P<0.0001). Information on endocrine responsiveness before primary systemic therapy will lead to better tailoring of treatment modalities, thus avoiding chemotherapy in selected populations where other approaches (e.g. endocrine primary therapy) might be more useful.
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PMID:Preoperative systemic treatment: prediction of responsiveness. 1465 32

It still needs to be verified whether multiple syncronous homolateral and bilateral breast cancers represent intramammary spread of a single tumor or two or more separate neoplastic events. To clarify this problem, we studied the biopathological profile of 46 homolateral and 20 bilateral cases. The cancers were always surgically removed and processed at the same time. The expression of estrogen receptors (ER), progesterone receptors (PR), MIB 1, p53, and c-erbB-2 was determined. Computer-assisted image analysis (CAS 200) was used to evaluate ER, PR, MIB 1, and p53. The histological concordance was 95.6% in homolateral and 50% in bilateral cases. The immunophenotype profile of multiple homolateral neoplasms showed a concordance between 93.47% for ER and 78.26% for p53. The results were statistically significant for all parameters except for p53. In bilateral cancers, there was a significant statistical concordance for ER. These data strongly suggest that both mechanisms may exert an influence and, in particular, that in the majority of homolateral carcinomas, there may be intramammary spread of tumor cells. In multiple bilateral tumors, however, the great diversity of the histological aspects and the differences in the immunophenotype pattern suggest that the vast majority of these may constitute independent multiple events.
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PMID:Biopathological profile of multiple synchronous homolateral and bilateral breast cancers. 1515 45

The purpose of the present study was to analyze the relation between the expression of p53, bcl-2, p21WAF1, MIB-1, HER-2/neu, DNA ploidy and HPV16 or 18 infections with clinical parameters. HPV-DNA was evaluated in 171 early cervical carcinomas treated from 1965 to 1990 and detected by PCR (polymerase chain reaction) on paraffin specimens obtained before therapy was started. HPV-DNA of any type was detected in 78% (86/110) of all tumors, HPV16 was the predominant type and was seen in 56% (62/110), HPV18 in 8% (9/110) and HPV35 in 21% (23/110). Patients with HPV16 or 18 were significantly (P=0.011) younger than patients with tumors not containing these two HPV subtypes. Lymph node metastases were seen more frequently (P=0.047) in tumors expressing HPV16 or 18. Tumor size was associated with the HPV-type. The frequency of DNA aneuploidy was lower in high-risk HPV tumors than in tumors with other HPV subtypes (P=0.014). MIB-1 expression was highly significantly (P=0.00007) associated with presence of HPV16 or 18. The cancer-specific survival rate was lower for patients with HPV16 and 18 positive tumors, but the difference was not statistically significant. The overall 5-year survival rate of the complete series was 91%. In conclusion, the HPV DNA subtype was a prognostic factor in early stage cervical cancer and it was associated with age, positive lymph nodes, tumor size, DNA ploidy and the proliferation marker MIB-1.
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PMID:Relation between HPV-DNA and expression of p53, bcl-2, p21WAF-1, MIB-1, HER-2/neu and DNA ploidy in early cervical carcinoma: correlation with clinical outcome. 1520 79

The antiestrogen tamoxifen, a major endocrine therapy of estrogen receptor (ER)-positive breast cancer, is nevertheless inefficient in 30 to 40% of cases for unknown reasons. We retrospectively studied 50 ER-positive primary breast carcinomas. All of the patients had received tamoxifen as the only adjuvant therapy. They were divided into two groups depending on whether they relapsed within 5 years (16 tamoxifen-resistant cases) or did not relapse within 5 years (34 tamoxifen-sensitive cases). The expression of total ER beta protein, and of ER beta cx protein, was estimated anonymously in formalin-fixed, paraffin-embedded tumor sections, by using specific antibodies and quantifiying nuclear immunostaining with a computer image analyzer. All of the tumors were found to be HER-2/neu-negative by immunohistochemistry. Univariate analysis showed that Scarff-Bloom-Richardsson grade modified by Elston (SBR grade; P < 0.001), tumor size (P = 0.042), and MIB-1 proliferation index (P = 0.02) were significantly higher in tamoxifen-resistant tumors. A low level of total ER beta, whether in percentage of positive cells or in quantitative immunocytochemical (QIC) score, was also associated with tamoxifen resistance (P = 0.004). ER beta cx expression and lymph node status were similar between the two groups. The expression of ER beta in the total population was positively correlated with ER beta cx (r = 0.63, P < 0.001), and was independent of the other parameters. In a multivariate analysis, ER beta expression was the most important variable (P = 0.001), followed by SBR grade (I+II versus III; P = 0.008), and MIB-1 (P = 0.016). To conclude, tamoxifen resistance is associated with classical variables of aggressive tumors (high SBR grade, proliferation index, and tumor size) but not with node invasiveness. Low ER beta level is an additional independent marker, better than ER alpha level, to predict tamoxifen resistance.
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PMID:Estrogen receptor beta (ER beta) level but not its ER beta cx variant helps to predict tamoxifen resistance in breast cancer. 1535 5

The objective of the present investigation was to study the expression of c-erbB-2 and MIB-1 and try to associate them with morphological features of the cell such as nuclear pleomorphism, mitotic count and histological grade in a series of 70 canine mammary gland tumors, 22 of them benign and 48 malignant. Tumors were collected at the Veterinary Hospital of UFMG (Brazil) and the Veterinary Faculty of Porto University (Portugal). c-erbB-2 expression was determined according to the guidelines provided by the manufacturer of the HercepTest system and nuclear pleomorphism, mitotic count and histological grade according the Elston and Ellis grading system. The HercepTest is the FDA-approved in vitro diagnostic test marketed by Dako. It is a semi-quantitative immunohistochemical assay used to determine overexpression of HER2 protein (human epidermal growth factor receptor) in breast cancer tissue. MIB-1 expression was also evaluated in 28 malignant tumors. Seventeen (35.4%) of the malignant tumors were positive for c-erbB-2 expression, which was positively associated with nuclear pleomorphism (P < 0.0001), histological grade (P = 0.0017) and mitotic count (P < 0.05). Nuclear pleomorphism also showed a positive association with MIB-1 index (P < 0.0001). These results suggest that some of the biological and morphological characteristics of the tumor are associated in canine mammary gland tumors, as also reported for human breast cancer. It was also possible to show that the immunoexpression of c-erbB-2 can be a factor in mammary carcinogenesis. This fact opens the possibility of using anti-c-erbB-2 antibodies in the treatment of canine mammary tumors.
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PMID:c-erbB-2 expression and nuclear pleomorphism in canine mammary tumors. 1578 24

VEGF is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis in physiological and pathological conditions. Nevertheless, VEGF tissue evaluation in cancer patients as a prognostic factor compared to the conventional histological and biological parameters is still controversial. In this case-control study, tissue VEGF was retrospectively determined by immunohistochemistry and related to T, N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 in 129 breast cancer patients. Seventy-four of these patients had developed distant metastases postoperatively. The remaining 55 patients had remained disease-free >10 years after surgery. In 17 (13%) of the 129 patients (six with distant metastases and eleven disease-free) tissue and plasma VEGF were concomitantly evaluated. In univariate analysis no significant differences in VEGF and tumor size were found between metastatic and disease-free patients, whereas there were significant differences in N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 (p ranging from 0.001 to 0.0001). In multivariate analysis VEGF showed less significance than N, ER, c-erbB-2, MIB-1 and cyclin D1 (p = 0.012, p = 0.007, p = 0.005, p = 0.005, p = 0.002 and p = 0.001, respectively). VEGF was a significant unfavorable prognostic indicator only in the N+ subset (p = 0.015), while ER (p = 0.05 and p = 0.021) and MIB-1 (p = 0.031 and p = 0.022) were significant in both the N+ and N- subgroups. In multivariate analysis in the 74 metastatic cases VEGF did not show any significance in relation to disease-free interval and overall survival from the time of mastectomy and from the time of relapse, whereas N and PgR did (p ranging from 0.018 to 0.001). In conclusion, tissue VEGF does not seem a suitable candidate to replace conventional histological and other common biological prognostic factors in breast cancer.
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PMID:Vascular endothelial growth factor (VEGF) and other common tissue prognostic indicators in breast cancer: a case-control study. 1564 33

Here, the structure, function, biological and pathological significance and clinical utility of the principal biomolecular markers of breast cancer is reviewed. Each marker was scored for clinical utility using a recently developed tumor marker utility grading system (TMUGS). Among the tissue markers, ERs and PRs are important prognostic/predictive factors and the only tissue markers routinely determined. ER cross-talks with other growth factors while co-regulatory factors enhance (co-activators) or decrease (co-repressors) its transcriptional activity. C-erbB-2 and Ki67/MIB-1 select for adjuvant chemotherapy a subgroup of lymph-node negative patients at a high risk of relapse. Monoclonal antibodies (trastuzumab, gefitinib, erlotinib and bevacizumab) targeting tissue markers and involved in tumor growth and metastasization (EGFR, C-erbB-2, VEGF) have been developed; they showed therapeutical single agent activity as well as potent synergy with chemotherapy agents in metastatic cancer. Among circulating markers, some are potentially useful in the early detection and monitoring of metastatic disease; nevertheless, none is routinely recommended. To suspect distant metastases, CEA-TPA-CA15.3 panel attained accuracy of about 90%. ECD HER2-neu, p53 and nucleophosmin antibodies seem suitable candidates for different associations. Preliminary observations suggest that an early detection with tumor markers and successive treatment of relapses significantly prolongs disease-free and overall survival in selected patients. In conclusion, biomolecular markers are improving understanding of biology and management of breast cancer.
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PMID:Biomolecular markers of breast cancer. 1636 59

Data regarding the biologic behavior and surgical management, in particular the axillary lymph node excision, of ductal carcinoma in situ with microinvasion (DCIS-MI) are controversial. Therefore, we decided to study the histopathologic characteristics, the biopathologic profile, as well as the follow-up of a group of patients with DCIS-MI. Thirty-one cases of DCIS-MI, 21 of whom were treated with axillary lymph node dissection, were studied. All cases were classified according to the Van Nuys classification, and the extension of DCIS was quantified. The biopathologic profile (ER, PR, MIB 1, p53, c-erbB-2) as well as the follow-up was also investigated. The results did not reveal any statistically significant differences between the two groups, and there was no statistically significant relationship between the extension of DCIS and the number of microinvasion (MI) foci or maximum MI diameter, or between Van Nuys classification of DCIS and again the number of MI foci or maximum MI diameter. DCIS-MI seems associated with good prognosis. None of the patients had relapses or metastases. Our data seem to suggest that the natural history of DCIS-MI resembles DCIS, and we, therefore, suggest that all the surgically removed area should be examined histologically to avoid missing foci of infiltrating breast cancer larger than 1mm.
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PMID:Ductal carcinoma in situ with microinvasion: clinicopathologic study and biopathologic profile. 1645 26


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