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)

Receptor status, proliferative activity, loss of differentiation, inactivation of tumor suppressor genes, and overexpression of oncogenes are related events that may affect the prognosis of patients with breast cancer. Ninety-seven unselected breast carcinomas were immunostained for estrogen and progesterone receptors, Ki-67 proliferation-associated antigen, p53 tumor suppressor gene product (p53), and c-erbB-2 protein. Immunohistochemical results and clinical data were compared. Altered p53 expression (regarded as indirect indication of inactivating gene alterations) was found in 25.8% of cases and was associated with a high Ki-67 labeling index, high mitotic count, and high histologic grade, with c-erbB-2 overexpression, and with negative estrogen and progesterone receptor status. p53 immunostaining could be found also in cytologic samples and correlated with p53 immunoreactivity on frozen sections of the corresponding tumors. c-erbB-2 protein overexpression was seen in 24.7% of cases and was associated with p53 altered expression and negative receptor status. Double immunohistochemical staining showed p53 and c-erbB-2 immunoreactivity in the same cells. Median and mean +/- standard deviation Ki-67 labeling index values were 15 and 16.32 +/- 10.05, respectively. Ki-67 labeling index was correlated with high mitotic count and was positively associated with histologic grade, negative progesterone receptor status, and p53 expression. Estrogen receptor status was not associated with any histologic or clinical parameters, whereas progesterone receptor status was associated with grading. The direct relation of p53 protein alterations with c-erbB-2 overexpression may be interpreted in light of the multistep model of tumor progression. Cases with altered expression of both p53 and c-erbB-2 proteins could be interpreted as having lost one inhibitory control mechanism of cell proliferation and having gained one activator of the malignant potential. However, in comparing cases with the p53 + c-erbB-2 + phenotype with cases showing positivity for only one of these gene products, no association with higher stages was seen. Detection of p53 altered expression on cytologic samples of malignant tumors may have diagnostic relevance, and p53 immunostaining may prove to be an additional diagnostic criterion in cytologic diagnosis.
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PMID:p53 and c-erbB-2 protein expression in breast carcinomas. An immunohistochemical study including correlations with receptor status, proliferation markers, and clinical stage in human breast cancer. 135 56

Biologic properties of breast cancer in men that might reflect alterations in pathogenesis from the disease in women were examined. We studied 22 tumors from males, 18 invasive carcinomas, three of which were papillary, and three in situ tumors of which one was papillary, and one papilloma. Our data support the previously reported high incidence of papillary carcinoma in men. Estrogen receptor status and the expression of cancer-associated antigens recognized by antibodies DF3, B73.2, SP-1, and c-erbB-2 were compared to matched tumors from females. Immunocytochemistry was performed on formalin-fixed, paraffin-embedded sections using standard avidin-biotin techniques; anti-PSA was used to exclude the possibility of metatastic prostate cancer, and 12 cases of gynecomastia were included as nonmalignant controls. The incidence of estrogen receptor positivity was higher in tumors from males (73%) than from females (54%), as has been reported previously. The range of expression of all breast cancer antigens tested in male tumors was similar to that observed in females, but some interesting differences were noted. With the exception of the anti-mucin DF3, all the antibodies reacted only with neoplastic tissues. Expression of the oncoprotein c-erbB-2 was lower (17%) in males than in females (33%), despite the preponderance in men of the large-cell type carcinomas that have been associated with c-erbB-2 expression. Unexpectedly, the pregnancy-associated hormone detected by SP-1 was expressed in 33% of tumors from males and, in contrast to females, was found in less differentiated tumors.
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PMID:Immunocytochemical characterization of male breast cancer. 136 97

Material from 41 patients with primary breast carcinoma and lymph node metastases at the time of primary surgical intervention was immunostained for c-erbB-2 protein, neuron-specific enolase (NSE), and estrogen receptors. Thirty of the primary breast carcinomas were of ductal type. Six were classified as infiltrating lobular carcinomas, 2 were apocrine, 1 was mucinous, and 1 was a tubular carcinoma. One tumor could not be classified as ductal or lobular by light microscopic examination alone. The number of lymph node metastases available varied from 1 to 14 per case (median, 3.9). Nine (22%) of the primary breast carcinomas (8 ductal and 1 apocrine) expressed c-erbB-2 protein and showed c-erbB-2 gene amplification; 12 expressed NSE immunoreactivity. None expressed both markers. Estrogen receptor immunoreactivity was present in 23 of the 41 cases, including 9 of the NSE-positive cases. C-erbB2- protein-positive metastases were present in 18 cases (44%), and in 13 cases all metastases were immunostained. In 5 cases the expression of c-erbB-2 protein varied from metastasis to metastasis. NSE immunoreactivity was expressed in 10 cases, and in 3 cases with minor NSE-positive cell populations the metastatic lesions expressed c-erbB-2 protein as well. All 9 primary breast carcinomas expressing c-erbB-2 protein had lymph node metastases with c-erbB-2-immunoreactive tumor cells. Eight of the 9 c-erbB-2 protein-negative primary tumors with metastases expressing c-erbB-2 protein showed no amplification of the c-erbB-2 gene.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The c-erbB-2 protein in primary and metastatic breast carcinomas. 167 62

The expression of epidermal growth factor receptor (EGF-R), c-erbB-2 proto-oncogene, and estrogen receptor (ER) was studied immunohistochemically in a series of 97 human papillomavirus (HPV) lesions of the uterine cervix, with special emphasis on their association with the HPV type, grade of intraepithelial neoplasia (CIN), and the natural history of the disease. EGF-R expression was found in 95 of 97 (98%) specimens, mainly in basal and parabasal cells. Diffuse nuclear and cytoplasmic staining was detected in 36 of 97 (37%) samples, of which 29 were HPV positive. This staining pattern was most prominent in HPV 18-positive and in CIN lesions. Weak or moderate c-erbB-2 expression was found in 26 of 97 (27%) specimens. Estrogen receptor expression was observed in 28 of 77 (36%) samples, epithelial staining was seen in 11 of 77 (14%), and stromal staining occurred in 24 of 77 (31%) specimens. No clear-cut associations were established between the EGF-R, c-erbB-2, or ER expression and HPV type, nor in CIN or the clinical course of HPV infections. This failure for EGF-R, c-erbB-2, and ER to be associated with the specific HPV types, grade of CIN, or the clinical course of cervical HPV lesions suggests that the assessment of these factors is of limited value in explaining the development of HPV-associated CIN and in predicting the prognosis of this disease.
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PMID:Epidermal growth factor receptor, c-erbB-2 proto-oncogene and estrogen receptor expression in human papillomavirus lesions of the uterine cervix. 792 56

Estrogen receptor positive ovarian cancer is often refractile to antiestrogen therapy. Here we describe the SKOV3 human ovarian carcinoma cell line as an in vitro model for estrogen and antiestrogen resistant ovarian cancer. While SKOV3 cells expressed estrogen receptor (ER) mRNA and protein at a similar level as the estrogen responsive T47D breast carcinoma cell line, their growth was not responsive to estradiol (E2) and was not inhibited by the antiestrogens OH-tamoxifen and ICI 164,384. The ER in SKOV3 cells was normal with respect to apparent Kd for binding with E2, E2 regulation of a transiently transfected ERE driven reporter gene, and E2 stimulation of expression of the early growth response genes c-myc and c-fos. However, the SKOV3 cells exhibited no expression of the progesterone receptor gene (PR) even after addition of E2, and the protein products of the estrogen responsive genes HER-2/neu and cathepsin D were expressed at constitutive levels that were not regulated by E2. Therefore, estrogen resistance in these cells may be a result of constitutive expression and loss of E2 regulation of selected growth regulatory gene products rather than a defect in estrogen activation of ER as a transcriptional regulator.
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PMID:SKOV3 ovarian carcinoma cells have functional estrogen receptor but are growth-resistant to estrogen and antiestrogens. 854 Dec 24

p53, c-erbB-2 protein, steroid hormone receptors, and their correlation with clinicopathologic features were investigated in 70 primary breast carcinomas. All markers were measured immunohistochemically on paraffin sections. Altered p53 expression was found in 27.1% of cases and was associated with negative estrogen receptor status. p53 immunostaining was correlated weakly with histologically lymphatic vessel invasion of carcinoma. c-erbB-2 protein overexpression was seen in 48.6% of cases. A trend was observed in the correlation between c-erbB-2 immunostaining and regional lymph node metastases. Estrogen receptor status was not associated with any histologic or clinical parameters, whereas progesterone receptor status was associated with lymph node metastasis and histologically lymphatic vessel invasion of cancer. PgR status, p53 and c-erbB-2 immunostaining may prove to be an additional criterion in histologic diagnosis of breast cancer.
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PMID:c-erbB-2, p53 protein expression and steroid hormone receptors in breast carcinomas: an immunohistochemical study. 1062 45

A 49-year-old premenopausal woman with stage I breast carcinoma underwent left quadrantectomy with axillary dissection in 1992. The tumor was 0.7x0.5 cm Histopathologically, this was a pure tubular carcinoma without lymph node metastasis or lymphatic or vascular invasion. Although the surgical margin was pathologically negative, atypical ductal hyperplasia was present close to the cut margin's edge. Neither adjuvant chemotherapy nor radiotherapy had been given after the operation. Approximately 5 years after the first surgery, she had a local recurrence in the vicinity of the operative wound. There was no clinical evidence of distant metastasis. A salvage mastectomy was performed. Histopathological examination revealed that the second tumor was an invasive ductal carcinoma, histological grade 2, with extensive intraductal component. It was difficult to determine whether this was a true in-breast recurrence or a second primary cancer. Overexpression of p53 and c-erbB-2 was observed in the second tumor. Estrogen receptor and progesterone receptor were both negative. No postoperative chemotherapy was given. Multifocality and atypical ductal hyperplasia were observed in 7(87.5%)and 6(75%) of 8 patients, respectively, with tubular carcinoma between 1991and 1997 at the National Cancer Center Hospital. Coexisting disease associated with tubular carcinoma suggests that radiotherapy may be an important component of breast conservation treatment to prevent local recurrence in this type of tumor.
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PMID:Local Recurrence after Conservative Surgery without Postoperative Radiation for Pure Tubular Carcinoma of the Breast:A Case Report with Reference to Multifocality of Tubular Carcinoma. 1109 49

BACKGROUND: The causes and pathologic and prognostic phenotypes of late-onsetfamilial breast cancers are still unknown. The purpose of this study was to document the clinicopathological features of late-onset familial breast cancers using genetic testing of BRCA1 and BRCA2. METHODS: We analyzed 11 breast cancers from 10 patients from 8 Japanese late-onset Breast cancer families. RESULTS: The average age of the patients was 55 years (range 43 to 89). Bilateral occurrence was noted in 2 patients (8%). All the tumors were invasive ductal carcinomas, except for 1 case of invasive lobular carcinoma. Tumor size rangedfrom 0.8 cm to 7.8 cm (median 2.3 cm) and lymph node metastasis occurred in 6 of the 11 patients (55%). Six (55%) of the 11 tumors were histologically grade 2 and 5 (45%) were histologically grade 3. Estrogen receptor (ER) positivity was 80% (8/10). Overexpression of c-erbB-2 and p53 protein was detected in 18% (2/11)and 9% (1/11) of the tumors, respectively. Five patients from 4 families received genetic testing but all were negative for BRCA1 and BRCA2 germline mutations.All the patients were alive after a median follow-up period of 32 months, except for 1 patient. CONCLUSION: In this study, no germline mutations of BRCA1 or BRCA2 were detected. However, there was a tendency towards ER-positive tumors, but the positivity of p53 protein was considered to be lower then that of sporadic tumors.
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PMID:Japanese Late-Onset Breast Cancer Families: Their Clincopathological Characteristics and Absence of BRCA1 and BRCA2 Germline Mutations. 1109 55

Estrogen receptor-negative breast carcinomas are more aggressive and are unresponsive to anti-estrogens. Thus, they clearly require new therapies targeted against specific genes and proteins actively engaged in the pathophysiology of cancer. The S-phase kinase-associated protein Skp2 is required for the ubiquitin-mediated degradation of the cdk-inhibitor p27 and is a bona fide proto-oncoprotein. We attempted to explore whether Skp2 may be a potential specific therapeutic target in the subset of aggressive breast carcinomas by investigating the possible relationship between expression of Skp2 and p27 proteins and estrogen receptor (ER). Immunohistochemical analysis of tumor tissues was employed to determine the expression of Skp2, p27, and ER proteins in 82 cases of primary breast carcinoma. Higher levels of Skp2 were detected more frequently in ER-negative tumors and tumors metastatic to the axillary lymph nodes. The expression of p27 was inverse with the histologic grade. Statistical analysis showed that the percentage of high Skp2 expressors was significantly greater in the group with low p27 expression than in the group with high p27 expression. The current study, together with the results from a previous study, demonstrated the existence of a subtype of high-grade, negative ER breast carcinomas with high Skp2 and low p27 levels. This implies that Skp2 may be a potential specific therapeutic target in a subset of aggressive breast carcinomas. Thus far, there is no specific therapy for the ER-negative and HER-2/neu resistant groups, which are among the subset of aggressive tumors.
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PMID:Relationship between levels of Skp2 and P27 in breast carcinomas and possible role of Skp2 as targeted therapy. 1602 59

Breast cancer accounts for approximately 15% of all cancer deaths. Currently, axillary nodal status is the most reliable prognostic indicator for breast cancer. Tumor size and histological grade are used to stage breast cancer. Estrogen receptor/progesterone receptor (ER/PR) and HER-2/neu status are useful in predicting patient survival and relapse. Ki67, an indicator of proliferative activity, also correlates well with prognosis. Connexin proteins form gap junction channels, permitting intercellular exchange of ions and small molecules. Reduced connexin protein levels and impaired gap junctional intercellular communication are associated with tumor phenotypes. This study investigated the prognostic value of connexin proteins as breast cancer markers. Tissue microarrays, containing 438 cases of invasive breast carcinoma, were stained with Cx26, Cx32, and Cx43 antibodies. The degree of connexin immunoreactivity was determined and then correlated with patient outcome, tumor grade, tumor size, lymph node status, and immunohistochemical markers, such as p53, ER/PR status, Ki67 and c-erbB-2 expression. Cx26, Cx32, or Cx43 did not correlate well with tumor grade, tumor size, p53 or c-erbB-2 status. There was an inverse correlation between Cx32 and lymph node status (P <0.05) and a positive correlation between Cx43 and PR status (P <0.01). Cx32 and Cx43 correlated positively with ER status (P <0.01). Cx43 correlated negatively with Ki67 expression (P <0.01). Cx26, Cx32, and Cx43 did not correlate with patient outcome. Based on our observations in this study, connexin proteins do not appear to be reliable indicators of breast cancer prognosis.
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PMID:Tissue microarray analysis of connexin expression and its prognostic significance in human breast cancer. 1758 22


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