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 vascular endothelial growth factor (VEGF) appears to play an important role in tumor angiogenesis. The p53 and HER-2/neu genes have been thought to regulate VEGF expression. Although the most common genetic alterations described in human breast cancer are p53 gene mutations and HER-2/neu gene amplification, there is a paucity of reports concerning a possible association between VEGF expression and p53 and HER-2/neu expression. Ninety-nine invasive ductal carcinoma cases were examined by immunohistochemical studies with anti-VEGF, anti-p53, anti-HER-2/neu, and anti-CD34 antibodies. Computerized image analysis was used to evaluate the microvessel density (MVD). Eighty-eight tumors (88.9%) were classified as being VEGF positive. Twenty-five tumors (25.3%) showed p53 protein expression, while 36 tumors (35.4%) expressed the HER-2/neu protein. The MVD ranged from 22.0 to 197.0, with a median value of 58.5 (65.4 +/- 27.9). The tumors expressing VEGF had a significantly higher MVD than those that did not (P < 0.05). VEGF expression was significantly associated with p53 protein expression (P < 0.01). In double VEGF and p53 immunohistochemical stained sections, the two markers were generally expressed in the same tumor cells. The cancer stage was the only independent prognostic factor of disease-free and overall survival. The authors' results suggest that VEGF expression plays a role in promoting angiogenesis in invasive ductal carcinoma of the breast, and p53 is likely to be involved in regulating VEGF expression.
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PMID:Expression of vascular endothelial growth factor in invasive ductal carcinoma of the breast and the relation to angiogenesis and p53 and HER-2/neu protein expression. 1260 95

Young women with breast cancer have a more unfavorable outcome and advanced disease than older women. This study was initiated to determine the difference in tumor biology between younger and older groups. One hundred fifty-five patients with invasive ductal carcinoma, not otherwise specified, comprised the study group, including 50 women aged less than 35 years, 50 aged 36 to 50 years, and 55 aged more than 50 years. Histopathologic parameters, including tumor size, combined histologic grade, and axillary lymph node status, were studied. Biomarkers, including estrogen receptor status, tumor proliferation rate as determined by Ki-67, and gene expressions of c-erbB-2, p53, bcl-2, and BRCA1, were determined by immunohistochemistry. Comparisons of the distribution of these parameters in three age groups were performed. Breast cancer occurring in women aged less than 35 years had a significantly higher incidence of large tumor, high proliferation rate, and loss of nuclear BRCA1 expression (44.0% versus 22.0% or 23.6%) than in the two older age groups. Breast cancer in women aged less than 35 years also had higher histologic grade and higher frequency of bcl-2-negative tumor than that found in the 36- to 50-year age group. No difference was found in lymph node status and c-erbB-2 and p53 gene expressions between the age groups. Loss of BRCA1 nuclear expression significantly correlated with higher histologic grade and high Ki-67 index (P < 0.05) in group A. These findings suggested that women aged less than 35 years have frequent loss of nuclear BRCA1 expression, which may be responsible for the specific tumor biology different from older women. However, c-erbB-2 and p53 gene expressions seem to have no important role in the adverse tumor behavior of breast cancer in young women.
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PMID:Frequent loss of BRCA1 nuclear expression in young women with breast cancer: an immunohistochemical study from an area of low incidence but early onset. 1260 98

Our report describes a 66-yr-old man who underwent surgical resection of the pancreas twice within a period of 3 yr for primary and recurrent intraductal papillary mucinous tumors (IPMTs). During the second operation, a minute invasive ductal carcinoma (IDC) was accidentally discovered in the resected specimen of the residual pancreas. The similarity and continuity between this IDC and recurrent IPMT were not recognized histologically. A solid tumor was found in the hepatoduodenal ligament 3 mo after the second operation. We performed a third operation, performing laparotomy and intra-operative radiotherapy, but could not extirpate the tumor. A biopsy specimen obtained from the tumor during this third operation revealed adenocarcinoma, and the patient later died because of tumor progression. We immunohistochemically analyzed the expression of HER-2/neu, Smad4, p16, p21, p53, mucin immunophenotypes and the Ki-67 labeling index in this series of pancreatic-duct neoplasias. Overexpression of HER-2/neu and loss of Smad4 were detected in the minute IDC, which was very different from the immunohistochemical features of both the primary and recurrent IPMTs. The IDC also showed a MUC1-positive/MUC2-negative phenotype. Therefore, we suggest that de novo IDC may occur in IPMT patients, especially those with multiple tumor recurrence. The present case may be helpful in understanding the pathogenesis of pancreatic duct lesions.
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PMID:Minute invasive ductal carcinoma of the residual pancreas after distal pancreatectomy for intraductal papillary-mucinous tumor. 1262 31

Salivary duct carcinoma (SDC) is highly malignant salivary gland tumour with aggressive clinical behaviour, characterised by its histological resemblance to invasive ductal carcinoma of the breast. Amplification of gene HER-2/neu and overexpression of its gene product have been shown to have both prognostic and treatment implications in breast cancer. The reports concerning the expression of c-erbB2/HER-2/neu in salivary gland tumours are few and controversial. Thus, eleven cases of SDC were evaluated for HER-2/neu status using immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). To the best of our knowledge, this is the first molecular genetic analysis of SDCs using FISH. HER-2/neu overexpression, identified as strong membrane staining, was observed in all but one case of SDC in majority of neoplastic cells while only four tumours, of nine cases analysed, revealed HER-2/neu gene amplification by means of FISH analysis. SDCs were associated with poor clinical outcome, 6 patients (55%) died of disseminated carcinoma within 4 to 44 months after therapy. There was no difference in outcome of patients with IHC positive-nonamplified and IHC positive-amplified tumours.
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PMID:[Amplification and overexpression of HER-2/neu in parotid gland salivary duct carcinoma. Immunohistochemical study and fluorescence in situ hybridization]. 1267 94

As male breast cancer remains rare entity (less than 1% of cases of breast cancer), most of our current knowledge of it has been extrapolated from its female counterpart. The prevalence of male breast cancer increases with age, and the presentation occurs at an average age of approximately 60 years, 10 years older than in females with the disease. The majority of patients present with a painless, firm, subareolar mass, and the tumors are usually larger than 2 cm in diameter. There may be fixation to skin. Mammography and ultrasonography are useful to distinguish between breast cancer and gynecomastia. Pathologically, invasive ductal carcinoma is the predominant subtype, and lobular carcinoma is rare. Modified radical mastectomy is a principal surgical approach, and adjuvant therapy has been advocated in men based on the beneficial results of it in women. Hormonal manipulations constitute an essential part of adjuvant therapy, as male breast cancers have a high rate of hormone-receptor positivity. Although orchiectomy was practiced in the past, today, tamoxifen is the standard hormone therapy. With respect to systemic chemotherapy, the most common regimens are CMF (cyclophosphamide, methotrexate, 5-fluorouracil), or other anthracyclin-based regimens. In cases of disease recurrence, hormonal manipulations, chemotherapy, or radiotherapy can be administered for palliative purposes. Several selective aromatase inhibitors are now available; however, there are limited data regarding their efficacy in men. The prognosis does not seem to be poor compared to that of females when age and stage are matched. Further studies are needed to characterize the biologic and molecular properties of male breast cancer and their prognostic significance, and to devise optimal treatment strategies. However, it is interesting to note that p53 and c-erbB-2, are expressed and angiogenesis occurs in male breast cancer. Moreover, male breast cancer patients can carry BRCA2 mutations.
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PMID:[Male breast cancer]. 1279 89

PC-cell-derived growth factor (PCDGF, progranulin) is a novel autocrine growth factor that is overexpressed in human breast cancer cell lines. We have examined immunohistochemical PCDGF expression in 206 paraffin-embedded human breast lesions and investigated its association with clinicopathological variables. PCDGF staining was observed in breast carcinoma, whereas it was almost always negative in benign breast epithelium. PCDGF expression was more common in invasive ductal carcinoma (80% cases positive) than in invasive lobular carcinoma (53% positive). PCDGF staining was almost never observed in lobular carcinoma in situ. Ductal carcinoma in situ expressed PCDGF in 66% of the cases, and this expression correlated strongly with nuclear grade. Similar correlation was observed between PCDGF expression and histologic grade of invasive ductal carcinoma. Average Ki-67 index of PCDGF-negative/weakly positive invasive carcinomas (30.3) was significantly lower than that of strongly PCDGF-positive tumors (48.8, P=0.01). A larger percentage of tumors that expressed PCDGF with a staining intensity of 2+ or 3+ were p53 positive (44%) than were PCDGF-negative tumors (25%), P=0.02. PCDGF expression was independent of c-erbB-2 overexpression and of ER and PR status. Our study provides the first evidence of high incidence of PCDGF expression in human breast cancer in which it correlates with clinicopathological variables such as tumor grade, proliferation index, and p53 expression. These characteristics, as well as the virtual absence of expression in benign breast tissue, suggest an important role of PCDGF in breast cancer pathogenesis and make it a potential novel target for the treatment of breast cancer.
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PMID:Expression of PC-cell-derived growth factor in benign and malignant human breast epithelium. 1465 16

We attempted to compare the pattern of HER-2/neu, ER and PCNA in premenopausal and postmenopausal patients with breast carcinoma to identify potential biological differences. Five hundred and forty-eight samples from 318 premenopausal and 230 postmenopausal women with invasive ductal carcinoma of the breast were evaluated for HER-2/neu, ER and PCNA expression by immunohistochemistry. HER-2/neu expression showed 27.4% positivity in premenopausal and 24.8% in postmenopausal women; there was no significant difference between the two groups (p>0.05). In contrast, HER-2/neu expression was found to be significantly associated with ER negativity in the two groups (p<0.05 in premenopausal, p<0.001 in postmenopausal patients). However, it was significantly associated with PCNA expression only in the postmenopausal group (p<0.001). 54.4% showed premenopausal tumor cell ER positivity, whereas 64.3% of the postmenopausal group showed positivity. ER expression showed a significant correlation with patient menopausal status (p<0.05). The prevalence of PCNA positivity in the tumor cell components is slightly higher in postmenopausal compared to premenopausal women (p>0.20). The current study is consistent with reports from other groups regarding the correlation of HER-2/neu with adverse pathologic features and with expression of other markers in carcinoma. We also observed there was no trend toward increased HER-2/neu expression in either premenopausal or postmenopausal patients, i.e. there was similar HER-2/neu expression in the two groups. This suggests that HER-2/neu status could be used to determine assignment to specific intensive adjuvant therapy and evaluation of biological behavior in both pre- and postmenopausal patients with breast carcinoma.
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PMID:Comparison of HER-2/neu, ER and PCNA expression in premenopausal and postmenopausal patients with breast carcinoma. 1579 60

Pancreatic ductal carcinomas are thought to arise from precursor ductal lesions called pancreatic intra-epithelial neoplasias or PanINs. We report the case of a woman suffering from idiopathic chronic pancreatitis associated with PanINs lesions who developed six years later an invasive ductal carcinoma. Immunohistochemistry for p53, HER-2/neu and genetic analysis of K-ras oncogene were performed at different stages of disease and revealed that the PanINs and the carcinoma did not express p53 and HER-2/neu gene products whereas a K-ras mutation was present at the carcinoma stage. The relationship between cancer and chronic pancreatitis and the main difficulties concerning the early diagnostic of pancreatic cancer are discussed.
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PMID:From pancreatic intraepithelial neoplasia to cancer: a dramatic progression with K-ras status analysis. 1586 14

It was hypothesized that four histopathological types or subtypes of breast carcinoma were undifferentiated types characterized by bidirectional differentiation toward both luminal epithelial and myoepithelial cells and had characteristic molecular changes: invasive ductal carcinoma (IDC) with a large central acellular zone, atypical medullary carcinoma (a subgroup in Grade 3 solid-tubular carcinoma), matrix-producing carcinoma, and spindle-cell carcinoma (or carcinoma with spindle-cell metaplasia). In 32 cases of the undifferentiated type and 37 cases of the relatively differentiated types, we immunohistochemically examined the expressions of myoepithelial markers and KIT, epidermal growth factor receptor (EGFR), and c-erbB-2 oncoproteins. Vimentin, S-100, and alpha-smooth muscle actin were positive in 28 (88%), 22 (69%), and 15 (47%) of the undifferentiated types, but were positive in seven (19%), one (3%), and one (3%) of relatively differentiated types (P < 0.0001). KIT and EGFR overexpressions were detected more frequently in the undifferentiated types (34 and 88%, respectively) than in relatively differentiated types (3 and 3%, respectively) (P < 0.0001, for both). In 11 (85%) of 13 cases with KIT overexpression, EGFR overexpression concurred. c-erbB-2 overexpression was almost equally detected in both the undifferentiated and relatively differentiated types, and did not correlate with KIT or EGFR overexpression. Phosphotyrosine was detected in 16 (67%) of 24 cases with KIT, EGFR, and/or c-erbB-2 overexpression but only in six (18%) of 34 cases without KIT, EGFR, or c-erbB-2 overexpression (P = 0.0002). The undifferentiated-type breast carcinomas appeared to show mammary epithelial stem cell-like features, and they could be identified by KIT and/or EGFR overexpressions.
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PMID:Frequent KIT and epidermal growth factor receptor overexpressions in undifferentiated-type breast carcinomas with 'stem-cell-like' features. 1595 55

The purpose of this study was to evaluate cyclooxygenase-2 (COX-2) expression in the successive steps of breast carcinogenesis and to determine its correlation with HER-2/neu and p53 expression in invasive ductal carcinomas of the breast. Immunohistochemical staining with anti-COX-2 antibody was performed in normal breast tissue, usual hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Expression of COX-2 in invasive ductal carcinoma was correlated with immunohistochemical expression of HER-2/neu and p53 protein. COX-2 expression was found to be progressively elevated along the continuum from normal breast tissue to invasive ductal carcinoma (P<0.001). COX-2 expression significantly correlated with p53 and HER-2/neu protein expression (P<0.05 and P<0.001). On multivariate analysis, only TNM stage and elevated COX-2 expression correlated with survival. Our results suggest that COX-2 may be involved in the carcinogenesis of the breast and may be an independent prognostic indicator in patients with invasive ductal carcinoma. HER-2/neu and p53 are likely to be involved in the regulation of COX-2 expression in invasive ductal carcinomas of the breast.
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PMID:Expression of cyclooxygenase-2 in breast carcinogenesis and its relation to HER-2/neu and p53 protein expression in invasive ductal carcinoma. 1616 26


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