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)

Breast cancer has been the most common malignant tumor among women in many large cities of China. The aim of this study was to clarify the prognostic significance of serum anti-p53 antibodies (p53 Abs) in Chinese patients of breast cancer. One hundred and forty-four patients with invasive ductal carcinoma of breast were involved in this study. The expressions of ER, PR, c-erbB-2 and p53 were immunostained in tumor tissues and serum p53 Abs were assayed using ELISA method. The correlations between p53 Abs and other clinical and biological markers were analyzed. Among 144 patients, 31 (21.5%) had positive p53 Abs, which was associated with several poor prognostic parameters including higher clinical stage (p = 0.0233), lymph nodes metastasis (p = 0.0033), negative ER expression (p = 0.0250) and positive c-erbB-2 status (p = 0.0227). There was also a strong correlation between p53 Abs and tumor p53 positivity (p < 0.0001). These results indicated that the presence of p53 Abs is probably triggered by the accumulation of tumor p53 protein, and it could be a useful marker to complement routine prognostic factors in breast cancer patients.
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PMID:The presence of serum anti-p53 antibodies from patients with invasive ductal carcinoma of breast: correlation to other clinical and biological parameters. 1618 30

The basal phenotype of breast carcinoma was demonstrated from a study of gene expression profiles, which demonstrated five carcinoma phenotypes with differing immunohistologic profiles and outcomes. The basal phenotype, so-named because of an immunohistologic profile that is similar to myoepithelial cells of the breast, has poor outcomes. While the invasive basal phenotype has been described, there is a paucity of literature regarding the existence or recognition of a precursor lesion. We searched our CoPath database for breast carcinomas in the age group of 37 years or less, and this yielded 98 cases from the years 2001 to April 2006. Pathology reports were screened for those cases that were negative for estrogen and progesterone receptors and HER-2/neu (triple negative). A total of 16 cases (16/98, 16%) fulfilled these criteria. Histology was reviewed and immunostains were performed for Cytokeratins 14, 17, and 5/6, vimentin, EGFR, c-kit, smooth muscle actin and p63. All 16 cases had a high-grade invasive ductal carcinoma, Nottingham score 9/9, with geographic necrosis, good circumscription and lymphoid infiltrates. Of the 16 cases, 13 exhibited at least one area of ductal carcinoma in situ (DCIS). The DCIS types were solid, flat or micropapillary, high nuclear grade, with comedonecrosis and invariably associated with intense lymphoid inflammatory cell infiltration. Of 16 invasive cases, 14 (88%) were positive for CK14, CK17, CK5/6 and EGFR; 94% were vimentin positive, while half or less of cases were positive for smooth muscle actin, c-kit or p63. All of the DCIS components demonstrated the same immunohistologic profile as the invasive component. A DCIS component of solid, flat or micropapillary type exists in the basal phenotype of breast carcinoma, and it demonstrates the same immunophenotype as the invasive carcinoma, typically positive for CK5/6, CK14, CK17, vimentin and EGFR, but negative for ER/PR and HER-2/neu.
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PMID:Basal phenotype of ductal carcinoma in situ: recognition and immunohistologic profile. 1694 Oct 11

This retrospective hospital-based study aimed to describe health conditions and to estimate the survival of 252 patients diagnosed with breast cancer and treated at the Mastology Outpatient Clinic at the University Hospital of the Federal University in Santa Maria, Rio Grande do Sul, Brazil, from 1980 to 2000. Analysis followed the Kaplan-Meier and Cox model. Mean age was 54, and 73.4% of the patients had a histological diagnosis of invasive ductal carcinoma, 63.9% showed no lymph node involvement, and 57.6% were clinical stage II. At the end of the study, 64.7% were alive and free of breast cancer and 5.1% had died of other causes. Five-year survival was 87.7% for all women, and prognostic factors associated with survival were tumor size (HR = 12.03; > 5cm), lymph node involvement (HR = 3.08; N1) and number (HR = 4.66; None), and estrogen (HR = 0.34) and c-erbB-2 (HR = 2.51) receptors. Based on the results, intensive awareness-raising campaigns are vitally important for implementing breast cancer screening to achieve early diagnosis.
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PMID:[Survival study of breast cancer patients treated at the hospital of the Federal University in Santa Maria, Rio Grande do Sul, Brazil]. 1695 94

The study group was derived from the archival materials of 48 invasive intraductal breast cancer patients who had undergone partial mastectomy/ axillary dissection. All patients included in the study had clinically T1-2N0M0 invasive ductal carcinoma. To detect HER-2/neu status, fluorescent in situ hybridization was performed using a HER-2/neu locus-specific probe. Signals were counted and patients were classified in three groups according to signal ratios: signal ratio <2, group 1 (n=31); signal ratio 2-4, group 2 (n=11); signal ratio >4, group 3 (n=6). Ratios of axillary metastatic lymph nodes to dissected total lymph nodes were 17%, 23% and 83% in groups 1, 2 and 3 respectively (P=0.003). The number of metastatic axillary lymph nodes, and the ratio of microscopic metastatic lymph nodes were highest in group 3 (P=0.001 and P=0.008, respectively). No significant difference was observed between groups for distant metastasis in a 5-year follow-up period. Signal ratios decreased with estrogen receptor expression (P=0.03). Histopathologically, an irregular growth pattern of the tumor was observed in 100% of the patients in group 3, and in 54% and 60% in groups 1 and 2, respectively (P=0.04). Lymphovascular invasion of the tumor was significantly higher in group 3 compared to the other two groups (P=0.01). The extensive intraductal component ratio was the highest in group 3 (P=0.04). The appearance of desmoplastic reaction and lymphocyte infiltration did not show significant difference between the groups. Our results show that HER-2/neu signal ratio increases with lymphovascular invasion, an extensive intraductal component, irregular growth pattern and axillary metastasis in clinically T1-2N0M0 invasive ductal carcinoma of the breast.
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PMID:Clinical findings and HER-2/neu gene amplification status of breast carcinoma patients. 1718 83

Ductal carcinoma in situ (DCIS) of the breast shows unpredictable association with invasive ductal carcinoma (IDC). Comedo DCIS (CDCIS) is more frequently associated with IDC than noncomedo DCIS (NCDCIS). We studied prognostic variables in 64 cases of DCIS to identify predictors of invasion. These factors included DCIS type and nuclear grade and two counts of the AgNOR silver staining technique for identification of ploidy and proliferative activity (PA) using two counts: mAgNOR for ploidy and pAgNOR for PA. The other factors included immunostaining of the lesions for epidermal growth factor receptors (EGFR), cathepsin-D (C-D), and the c-erbB-2 oncogene. The 34 cases associated with ICD had pAgNOR ranging from 3% to 36% (median 11%), whereas cases not associated with IDC had a pAgNOR range of 0% to 25% (median 5%; P=0.0001). The correlation between mAgNOR and the development of IDC was less statistically significant. The DCIS type and staining pattern for EGFR, C-D, and c-erbB-2 showed no statistical correlation of individual variables with the development of IDC. A scoring system adding the values of the seven variables was used. A score of 1-2 was given to each variable, depending on whether it was positive or negative. Lesions associated with IDC had a median total score of 8 (+/- 1.35 SD), whereas those lesions not associated with invasion had a median score of 4 (+/- 1.45 SD; P=0.0002). We conclude that proliferative activity analysis may play a significant role in predicting the invasive potential of DCIS. The use of a scoring system adding the sum of single prognostic indicators may provide more useful information regarding the prediction of invasive potential of DCIS than single indicators.
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PMID:Predictors of invasion in ductal carcinoma in Situ of the breast: The value of a scoring system. 1735 95

Previously, we showed that pure ductal carcinoma in situ (DCIS) of the breast can be divided into 3 subtypes (luminal, basal/stem, and null) based on the expression of 5 cytokeratin (CK) markers: CK5/6, CK14, CK17 (stem/basal), and CK8, CK18 (luminal). The distributions of CK subtypes were associated with nuclear grade and differential expression of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), HER-2/neu, and epidermal growth factor receptor (EGFR). In this study, we further explore the expression patterns of CK markers, ER-alpha, PR, HER-2/neu, and EGFR by immunohistochemical (IHC) analysis of 99 cases of pure DCIS and 96 cases of DCIS with co-existing invasive ductal carcinoma (DCIS/IDC). We show that between high-grade DCIS and DCIS/IDC, there are differential expression patterns for ER-alpha, PR, and EGFR in corresponding CK subtypes, suggesting that at least some pure DCIS is molecularly distinct from DCIS/IDC. In most cases there is a high degree of co-expression of these markers between DCIS and the co-existing IDC, suggesting that DCIS is frequently a precursor lesion for co-existing IDC. The rate of discordant expression of these markers is low and is more frequently associated with high-grade carcinoma, suggesting that other molecular pathways also may also be present. There are significant differences in the expression of these molecular markers between high-grade and non-high-grade carcinomas, supporting the view that high-grade and non-high-grade carcinomas of the breast are molecularly distinct entities.
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PMID:Expression of cytokeratin markers, ER-alpha, PR, HER-2/neu, and EGFR in pure ductal carcinoma in situ (DCIS) and DCIS with co-existing invasive ductal carcinoma (IDC) of the breast. 1752 67

The definition of high risk patients with early stage breast cancer is still controversial. We evaluated the ability of galectin-3, c-erbB-2 and p53 immunohistochemical expression to predict recurrence and survival in a homogeneous set of 92 patients with T1N0M0 ductal carcinoma with a long-term follow-up. In normal breast tissue, the epithelial and fibroblast components were positive for galectin-3 mostly showing nuclear and cytoplasmic reactivity. At the tumor epithelial component, galectin-3 expression was found in 46.7% of the samples with a predominant cytoplasmic staining. Similar results were presented by concurrent in situ lesions. Tumor stromal fibroblasts maintained positivity in 70 out of 92 cases (76%). We found expression of p53 in only 16 cases (17.4%), and c-erbB-2 in 17 (18.48%). A marginal association was found between co-expression of p53 and galectin-3 (p=0.055) and a significant correlation between p53 accumulation and c-erbB-2 expression (p=0.009). There was no significant association between galectin-3 protein expression with disease-free survival or overall survival. C-erbB2 and p53 expression correlated with recurrence (p=0.002, p=0.02; respectively). Diminished overall survival at 10 years was associated with c-erbB-2 (p=0.010), but marginally with p53 expression (p=0.076). Epithelial galectin-3 expression cannot be considered a prognostic factor for patients with T1N0M0 breast cancer, p53 seems to be of minor relevance and c-erbB-2 expression was the best discriminator and may be a marker for aggressive clinical behavior in patients with early stage breast cancer.
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PMID:C-erbB-2 expression is a better predictor for survival than galectin-3 or p53 in early-stage breast cancer. 1754 56

Breast carcinoma is one of the most common malignancies in women, and its carcinogenesis is still unknown. The role of microsatellite instability (MSI) in breast carcinogenesis has been inconsistent in the literature. Here we studied the expression of 2 mismatch repair genes, hMLH1 and hMSH2, in 211 cases of intraductal (DCIS; 90 cases) and invasive ductal carcinoma (121 cases) of the breast by immunohistochemical analysis; and evaluated its relationship with cytokeratin (CK) subtypes, along with expression of ER-alpha (138 cases positive, 73 cases negative); PR (118 cases positive, 93 cases negative), and HER-2/neu (47 cases positive, 164 cases negative); and clinical features such as patient age (157 cases>50 years, 54 cases<50 years), tumor size (31 cases of IDC>2 cm, 90 cases of IDC<2 cm), tumor grade (87 cases high nuclear grade, 124 case non-high grade), and lymph node metastasis (38 cases of IDC positive, 74 cases of IDC negative, 9 cases of IDC with no available data on lymph node status). For CK subtypes, 167 cases were classified as luminal subtype (expressing CK8 and/or CK18, negative for CK5/6, CK14, and CK17) and 44 cases were classified as nonluminal (most of them belonged to basal/stem subtype, expressing CK5/6, and/or CK14, and/or CK17). No typical or atypical medullary carcinoma was included in this study. Our results showed that no loss of nuclear expression of either hMLH1 or hMSH2 was identified in any of the 211 cases of DCIS or IDC regardless of the various pathological and clinical factors, suggesting that hMLH1 or hMSH2 may not play an essential role in the majority of cases of the breast carcinoma.
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PMID:Mismatch repair genes hMLH1 and hMSH2 may not play an essential role in breast carcinogenesis. 1765 29

E-cadherin (E-CD) is an epithelial-specific cell adhesion molecule, whose expression is lost in invasive lobular (ILC) but not in invasive ductal carcinoma (IDC) of the breast. This cell adhesion system can be disrupted by tyrosine kinase c-erbB-2/HER-2/neu. We examined 106 cases of high-grade invasive breast cancer, including 91 IDCs, 12 ILCs and 3 pleomorphic lobular carcinomas (PLCs). We determined Nottingham histological grade and performed immunohistochemistry for estrogen and progesterone receptors (ER/PR), Ki-67, E-CD and c-erbB-2/HER-2/neu with subsequent fluorescence in situ hybridization. Amplification of c-erbB-2/HER-2/neu gene was observed in 55/91 (60.4%) of IDCs, 3/12 (25%) of ILCs and 1/3 (33.3%) of PLCs, and associated with positive axillary lymph nodes. E-CD expression was lost in 14/91 (15.4%) of IDCs, 10/12 (83.3%) of ILCs and 2/3 (66.7%) of PLCs. The loss of E-CD immunoreactivity in IDCs appeared to be associated with c-erbB-2/HER-2/neu gene amplification, negative ER/PR status and positive lymph nodes, whereas E-CD-positive ILCs tended to be HER-2/neu-positive. The biological significance of E-CD expression seems to be different in high-grade IDC and ILC. Oncogenic pathway mediated by c-erbB-2/HER-2/neu may affect the E-CD expression in most invasive ductal breast carcinomas in vivo.
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PMID:Expression of E-cadherin and c-erbB-2/HER-2/neu oncoprotein in high-grade breast cancer. 1782 36

Salivary duct carcinoma (SDC) shares significant morphologic and immunophenotypic overlap with ductal carcinoma of the breast, including HER-2/neu expression. Previous studies have detected HER-2/neu at the protein level in SDCs; however, no study, to date, has assayed whether this expression is related to gene amplification detected by chromogenic in situ hybridization (CISH). Formalin-fixed, paraffin-embedded tissue sections from 12 previously diagnosed SDCs were evaluated by immunohistochemistry (IHC) and CISH for HER-2/neu status. Result concordance was seen in all 12 cases. A total of 4 SDCs were positive by IHC; all 4 cases showed amplification with CISH. The remaining 8 cases were negative by IHC and showed no gene amplification with CISH. SDCs in this study show HER-2/neu overexpression on both the protein and gene levels in approximately 30% of cases. These findings suggest a role may exist for Herceptin (trastuzumab) based therapy in some SDC patients.
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PMID:Her-2/neu expression in salivary duct carcinoma: an immunohistochemical and chromogenic in situ hybridization study. 1809 19


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