Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using permanent-section immunohistochemistry, we investigated the role of HER-2/neu in the development and progression of human breast cancer by measuring its overexpression in a series of hyperplastic (n = 30), dysplastic (n = 15), and malignant neoplastic (n = 708) lesions of ductal epithelium and by evaluating the relationships between overexpression and clinicopathologic features known to have prognostic significance in these lesions. The neoplasms included pure ductal carcinoma in situ (DCIS; n = 59) and infiltrating ductal carcinoma (IDC; n = 649). The latter were all node negative and stratified into IDC combined (n = 237) or not combined (n = 412) with a "significant amount" of DCIS (defined as DCIS greater than or equal to 10% of total tumor cellularity). Overexpression of HER-2/neu was not observed in any of the hyperplastic or dysplastic lesions. In contrast, it was present in 56% of pure DCIS and in 77% of the comedo subtype of this group. Only 15% of IDC overexpressed HER-2/neu. However, the rate of overexpression was significantly higher in the subset of IDC combined with DCIS compared with the subset of IDC not combined with DCIS (22% v 11%, respectively; P less than .0001). These results are consistent with the hypothesis that HER-2/neu plays a more important role in initiation than in progression of ductal carcinomas. They also suggest that overexpression decreases within individual tumors as they evolve from in situ to increasingly invasive lesions or, alternatively, that many invasive carcinomas arise de novo (ie, without progressing through a significant in situ stage) by mechanisms not involving HER-2/neu. In addition, overexpression of HER-2/neu was associated with several poor prognostic features (younger patient age, premenopause, negative estrogen receptor status, negative progesterone receptor status, and high nuclear grade) in the subset of IDC combined with DCIS. With one exception (negative estrogen receptor status) these associations were lost in IDC not combined with DCIS, also suggesting that the role of HER-2/neu changes during the progression of human breast cancer.
 ...
PMID:Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. 135 64

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.
 ...
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

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.
 ...
PMID:Mismatch repair genes hMLH1 and hMSH2 may not play an essential role in breast carcinogenesis. 1765 29

The aims of this study were twofold: (i) to determine the occurrence frequency of apocrine carcinoma of the breast (ApBCa) in Turkish breast cancer (BCa) patients; and (ii) to evaluate the expression of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), gross cystic disease protein-15 (GCDFP-15), c-erbB-2, and p53 in these cases. Six hundred and twenty-six cases of BCa were studied immunohistochemically (streptoavidin-biotin horseradish peroxidase method). The results of ApBCa were compared with those of invasive ductal carcinoma not otherwise specified type (IDC-NOS) cases of similar grade. Thirteen cases of ApBCa were encountered, accounting for 2.1% of all BCa cases. Immunohistochemically, ApBCa positivity was as follows: GCDFP-15 (100%), ER (39%), PR (8%), AR (54%), p53 (39%), and c-erbB-2 (85%). In the IDC-NOS group, GCDFP-15* was expressed in less than 50% of the tumors. The occurrence frequencies of the other markers were as follows: ER (69%), PR (69%)*, AR (46%), c-erbB-2 (0%)*, and p53 (31%), (*) indicating significant differences between the two groups. For Turkish BCa patients, (i) the occurrence rate of ApBCa (2.1%) was high; and (ii) the following combination would allow for an immunohistochemical identification of ApBCa: GCDFP-15(+), c-erbB-2(+), and PR(-).
 ...
PMID:Apocrine carcinomas of the breast in Turkish women: hormone receptors, c-erbB-2 and p53 immunoexpression. 1834 52

It has been reported that pure ductal carcinoma in situ of the breast has morphologic differences from the in situ component of the invasive ductal carcinoma, as well estrogen and progesterone receptors expression according to their cytokeratin expression. However, there is no data comparing other tumor markers without using the cytokeratin expression. The objective of this study is to compare the expression of estrogen receptor (ER) and progesterone receptor (PR), HER-2/neu, p53, and Ki67 between pure ductal in situ carcinoma (pDCIS) and the in situ component of the invasive ductal carcinoma (DCIS + IDC) of the breast, and the in situ component to the invasive component of the same tumor (DCIS + IDC). The immunohistochemistry expression of the tumor markers was performed in 45 cases of pDCIS and DCIS + IDC, yielding a total of 90 cases. Statistical analysis was carried out using Fisher exact test, having a P < 0.05, and Kappa index (kappa) to assess intratumoral concordance. In DCIS + IDC, the in situ and invasive components did not show a significant difference and Kappa index (kappa) was high (0.7-1) for positive and negative expression. ER and PR were significantly different between the pDCIS and DCIS + IDC (ER: 86.7 vs. 66.7% P = 0.04; PR: 80% vs. 55.6% P = 0.02). These findings suggest that in situ component of DCIS + IDC and pDCIS are distinct conditions.
 ...
PMID:Are the pure in situ breast ductal carcinomas and those associated with invasive carcinoma the same? 1956 68

Pleomorphic carcinoma of the breast is considered a rare variant of high-grade ductal NOS carcinoma (NOS-IDC), and the prognosis is poor. However, its clinicopathologic features are not well-characterized. Using the criteria delineated in the World Health Organization breast tumor classification of 2003, ten cases of pleomorphic carcinoma were identified from 9794 NOS-IDC in our archived materials that were originally diagnosed as high-grade infiltrating ductal carcinoma of breast. To investigate the clinicopathologic characteristics and to elucidate the histologic diagnosis and differential diagnosis of this entity, we reviewed the pathology manifestations and clinical features of these cases and examined the tumor expression of ER, PR, PCNA, AE(1)/AE(3), p53, S-100, C-erbB-2, EMA, p63, and Bcl-2 by immunohistochemistry.
 ...
PMID:Clinicopathologic characteristics of pleomorphic carcinoma of the breast. 2001 46

The aim of this study was to investigate the clinicopathologic characteristics and prognosis value for molecular subtypes of low-grade breast carcinoma (LGBC) compared with grade one invasive ductal carcinoma-not otherwise specified (G1-IDC-NOS). A retrospective review of 688 LGBC and 1 037 G1-IDC-NOS patients was classified into four different molecular subtypes based on the IHC-based definitions for ER, PR, and c-erbB-2. In LGBC, lymph node metastasis, the percentage of III/IV TNM stages, the expression of Ki-67 and p53 in luminal A subtype were lower than in other subtypes (P<0.01). In addition, the variations of Ki-67 and p53 expression were observed in different subtypes of G1-IDC-NOS (P<0.01). Compared with G1-IDC-NOS, LGBC has higher proportion in the ER positive, PR positive, HER-2 negative, luminal A subtype, Ki-67 negative, and lymph nodes negative group (P<0.01). Furthermore, the overall survival of luminal A and luminal B is higher than triple-negative and HER-2/neu subtype both in LGBC and G1-IDC-NOS in 262 LGBC and 330 G1-IDC-NOS patients with proper follow-up. The classification of molecular subtype together with clinicopathologic factors can significantly improve the traditional prognosticators in predicting outcome for LGBC and G1-IDC-NOS. And it may contribute to guide the treatment for LGBC and G1-IDC-NOS in the future.
 ...
PMID:Clinicopathologic characteristics and prognosis for molecular subtypes in low-grade breast carcinoma: comparison with grade one invasive ductal carcinoma-not otherwise specified. 2231 Dec 62

HER-2/neu oncoprotein overexpression in breast cancer patients has an impact on prognosis and treatment methods so assessment of its status is therefore much needed. The study group consisted of 90 cases of mammary invasive carcinoma. The distribution of HER-2/neu immunoexpression for scores 0, 1+, 2+ and 3+ were 54.44%, 11.11%, 18.8% and 15.56% respectively. HER-2/neu -positive cases comprised 21.42% of patients less than 50-year-old compared to 14.47% of patients of 50-year-old or older. Tumor size was negative correlated with HER-2/neu immunoexpression: positive tumors comprised 37.5% of tumor larger than 5 cm and this percentage decreases with tumor dimension to 2.94% in tumors of 2 cm or less. Regarding the histopathological subtype of invasive mammary carcinoma, only some types were positive, like 17.57% of IDC NOS and one case of mixed ductal-lobular invasive carcinoma. The highest proportion (21.31%) of positive HER-2/neu cases presented high-grade carcinomas (GIII), comparing with well-differentiated (GI) that were all negative. Regarding the axillary lymph node status the lowest proportion of positive HER-2/neu cases was 4.54% in the absence of metastasis, and rises to 34.78% in cases with more than three axillary lymph nodes involved. HER-2/neu-positive tumors showed a low incidence of ER+ or PR+ cases unlike HER-2/neu -negative cases (35.71% vs. 83.05% for ER, respective 21.42% vs. 76.27% for PR). Therefore, in conclusion, HER-2/neu-positive tumors are significantly fewer than the negative ones, but these are found in younger women and are associated with: large tumor size, high grade of malignancy (GIII) and increased number of axillary lymph node involvement. HER-2/neu immunoexpression is related to histological subtype of invasive breast carcinomas. Hormonal status is negative related to HER-2/neu expression.
 ...
PMID:Invasive mammary carcinoma: assessment of HER-2/neu status by immunohistochemistry. 2318 40

Invasive micropapillary carcinoma (IMPC) of the breast is an uncommon, highly aggressive breast cancer that may occur in pure and mixed forms. Our aim in this study is to investigate the relationship between clinical, histopathologic, and immunohistochemical features of pure and mixed IMPC cases diagnosed and treated at our institution. One hundred and three IMPC cases diagnosed at our institution over a period of 19 years have been selected. Clinical, histopathologic features, as well as hormone status and c-erb-B2 overexpression of tumors were re-evaluated. Mann-Whitney U, chi-squared, Kaplan-Meier, and Fisher's exact tests were used for statistical analyses. Results were considered to be significant at p < 0.05. Twenty cases (19.4%) were pure, and 83 cases (80.6%) were mixed IMPC. The most common nonmicropapillary invasive carcinoma component in mixed cases was invasive ductal carcinoma (IDC; 78.3%). Progesterone receptor was significantly less positive in pure IMPC cases (p = 0.031). There was no statistically significant difference between the two groups, in terms of mean age of the patients (53.0 versus 52.8), mean tumor size (26.6 mm versus 27.7 mm), presence of high-grade tumor (p = 0.631), presence of sentinel lymph node (SN) metastasis (p = 1.000), axillary lymph node metastasis (p = 1.000), lymphatic invasion (p = 1.000) and blood vessel invasion (p = 0.475), c-erbB-2 overexpression of tumor cells (p = 0.616), distant metastasis (p = 0.549), or overall survival (p = 0.759). The local recurrence rate of the two groups was not statistically significant either (16.7% versus 4.3%). However, local recurrence was detected 12% more commonly (p = 0.100), and ~8 months earlier (p = 0.967) in pure IMPC cases, compared to mixed cases. In addition, presence of local recurrence was found to be statistically significantly associated with estrogen receptor (ER) status (p = 0.004), progesterone receptor (PR) status (p = 0.001), and c-erb-B2 overexpression (p = 0.016) in all patients. Overall survival rate was significantly associated with ER staining of the tumor (log-rank = 0.028). Our findings suggest that hormone receptor negativity may explain the more aggressive behavior of pure IMPC compared to mixed cases. Besides, longer survival period of patients with ER positivity, and the relationship of hormone status and c-erb-B2 overexpression and local recurrence further support favorable prognostic value of hormone receptors in invasive breast cancer.
 ...
PMID:Invasive micropapillary carcinoma of the breast: a clinicopathologic study of 103 cases of an unusual and highly aggressive variant of breast carcinoma. 2371 6