雄激素受体在三阴乳腺癌的表达及临床意义

Background and Objective:Androgen receptor(AR) is involved in the pathogenesis of breast cancer,but its role is not clearly defined.This study was to explore the expression of AR and its relationship with clinicopathologic parameters in triple negative breast cancer(negative estrogen receptor,negative progesterone receptor,and negative Her-2).Methods:Immunohistochemical assays were performed to determine the expression of AR in 137 cases of triple negative breast cancer and 132 cases of non-triple negative ...     

AMACR Expression is a Potential Diagnostic Marker in Apocrine Lesions of Breast,and is Associated with High Histologic Grade and Lymph Node Metastases in Some Invasive Apocrine Breast Cancers

BackgroundCarcinoma with apocrine differentiation (AC) is a subtype of breast carcinoma with apocrine features in >90% of the tumor. Molecular studies demonstrate AC has high expression of androgen receptor (AR) mRNA. Pure AC lack estrogen receptor (ER), progesterone receptor (PR), and express AR, with variable human epidermal growth factor 2 (HER2) status. Currently, in triple negative AC, no targetable therapies or specific diagnostic markers exist.Materials and Methodsα-Methylacyl CoA racemase (AMACR) expression was investigated as a marker of apocrine differentiation using a single-plex immunoperoxidase stain, and a novel AMACR/p63 dual stain in a subset of cases, across 1) benign apocrine lesions (apocrine metaplasia, adenosis) 2) apocrine DCIS (ADCIS), 3) AC/ invasive ductal carcinoma (IDC) with apocrine features, 4) non-apocrine triple negative breast cancer (TNBC) and 5) IDC, no special type. A sub-set of cases were evaluated by tissue microarray.ResultsAMACR expression was increased in both AC and ADCIS, with minimal expression in benign breast tissue, TNBC and IDC, NST cases. In invasive cases, those with positive AMACR (>5% positivity) were significantly associated with higher histologic grade (P = .006), initial N stage (chi squared 0.044), and lack of ER or PR expression (both P < .001), with no correlation with overall survival. Analysis of TCGA breast cancer datasets revealed AMACR expression was significantly higher in molecularly defined apocrine carcinomas relative to basal and luminal subtypes. Moreover, high AMACR expression predicted worse relapse-free and distant-metastasis free survival, among both ER-/PR-/Her2- and ER-/PR-/Her2+ breast cancer cohorts (log-rank P = .081 and .00011, respectively).ConclusionAMACR represents a promising diagnostic and prognostic marker in apocrine breast lesions. Further study is needed to determine the biologic and clinical significance of this protein in AC.     

Overexpression of Her2/neu,estrogen and progesterone receptors in invasive micropapillary carcinoma of the breast

BACKGROUND: Invasive micropapillary carcinoma (IMC) of the breast is a rare subtype of breast carcinoma that has an extremely high incidence of lymph node metastasis and poor clinical outcome. Furthermore, there has been interest in the prognostic markers related to the biological characteristics of breast carcinoma, such as the status of Her2/neu, estrogen receptor (ER) and progesterone receptor (PgR). MATERIALS AND METHODS: We reviewed 671 cases of primary breast carcinoma which were surgically resected between 1990 and 2003. Of these, 27 cases of invasive ductal carcinoma of the breast with a pure or partial micropapillary component were reported. Tests for Her2/neu protein, estrogen receptor (ER) and progesterone receptor (PgR) were performed on paraffin sections. The relationship among these markers was analyzed and statistical significance determined by chi-square test. CONCLUSION: The rate of Her2/neu protein overexpression, ER and PgR status was quite similar to those of common breast carcinomas.     

Distribution, clinicopathologic features and survival of breast cancer subtypes in Southern China

Breast cancer research and treatment by different subtypes is an inevitable trend. We investigated the clinicopathologic features and outcomes of different breast cancer subtypes in Southern China. A total of 5809 patients with invasive ductal carcinomas were identified. Immunohistochemical (IHC) markers for estrogen receptor (ER), progesterone receptor (PR), Her2/neu, and Ki‐67 proliferation index were used to classify cases into five molecular subtypes. Clinicopathologic characteristics and survival rates were analyzed retrospectively. Of all patients, 31.1% were luminal A subtype, 30.4% luminal B (high Ki‐67), 13.1% luminal B (Her2/neu+), 9.0% Her2/neu and 16.5% triple negative subtype. Luminal B (high Ki‐67) presented primarily in premenopausal patients with the lowest average age (43.0 years). Her2/neu positive tumors were more closely associated with aggressive features including increased tumor size, positive lymph node status and lymphvascular invasion (LVI). Triple negative subtype was characterized by poorer histologic grade. Her2/neu positive cases had presented the worst 5‐year disease‐free survival (DFS) and overall survival (OS). Multivariate analyses of OS and DFS suggested that there were different negative prognostic factors for the five subtypes. The benefit of the cyclophosphamide, methotrexate, and 5‐fluorouracil (5FU) (CMF) regimen was equal to that of anthracycline‐based and Taxane‐based regimens for patients with luminal A subtype and triple negative subtype, but inferior to anthracycline‐based and Taxane‐based regimens for those with two luminal B subtypes and Her2/neu subtype. The prognostic significance of traditional markers may differ among subtypes. This study revealed the distinct clinicopathologic characteristics, systemic therapy benefits, prognostic factors and survival rate among different breast cancer subtypes.     

132例三阴性乳腺癌患者的临床特征与预后分析

目的探讨三阴性乳腺癌的临床特征及影响预后的因素。方法采用回顾性方法对我院132例三阴性乳腺癌患者的临床特征进行分析,并根据随访资料分析了患者的生存情况及预后因素。所有患者均经免疫组化证实ER、PR、Her-2为阴性。结果132例三阴性乳腺癌患者占同期乳腺癌患者（774例）的17．1％,绝经前患者（91例）占68．9％,53．8％的患者（71例）发病时肿块大小为T2,39．4％患者（52例）腋窝淋巴结阳性。中位随访时间63个月,共有33例出现复发或转移,其中20例死亡,23例同时出现2个部位以上的转移,5年的无病生存率为73．8％,总生存率为85．7％。淋巴结阳性患者复发转移风险较淋巴结阴性患者明显增加（P=0．001）。结论三阴性乳腺癌患者大多在治疗后2—3年发生多发转移,仅淋巴结状况是影响其预后的重要因素,淋巴结阳性的三阴性乳腺癌患者预后差。     

Androgen receptor expression in breast cancer: relationship with clinicopathological factors and biomarkers

Background  Breast cancer is a hormone-dependent tumor. Most breast cancer cells have an androgen receptor (AR), but the clinical value of AR expression is unclear. Methods  AR expression was evaluated in 227 primary breast cancers using immunohistochemistry. The relation of AR expression to clinicopathological factors and biomarkers was analyzed. AR expression was assessed semiquantitatively, and tumors with more than 10% of stained cells were regarded as positive. Results  The AR-positive rate was higher in smaller tumors (P = 0.045), tumors with negative lymph node metastasis (P = 0.045), scirrhous-type tumors (P < 0.0001), tumors of low histological grade (P = 0.0001), and p53-negative tumors (P = 0.0097). Although AR had no relation to menopausal status, 79% of cases of high AR expression (>50% stained cells) were in postmenopausal women. AR was related to estrogen receptor (ER; P = 0.027) and progesterone receptor (PR; P = 0.016) expression, but showed no relation to human epidermal growth factor receptor type 2 (Her2) expression. Regarding the coexpression of these receptors, 18 of the 42 cases of triple-negative (ER/ PR/ Her2-negative) tumors (43%) were AR-positive. Conclusion  AR expression is related to low malignancy in breast cancer. The assessment of AR expression may lead to new treatment strategies for breast cancer, especially in postmenopausal women and in women with tumors that show triple negativity for hormone receptors.     

Proliferative Index (Ki67) for Prediction in Breast Duct Carcinomas

Background and objectives: To date, many tumor markers have been used to predict prognosis and therapeuticresponse in patients with breast cancer. The well established and routinely applied tumor markers are the estrogen-receptor,progesterone-receptor and Her2/neu-receptor. In the current study, we aimed to highlight any association of theproliferation index (Ki67) in breast infiltrative duct carcinoma with the tumor grade, tumor size and nodal status inaddition to hormone receptor status. Tissue sections were stained immunohistochemically for Ki67 nuclear antigen,estrogen, progesterone and Her2/neu receptors using an automated Dako machine (Dako Denmark. There was asignificant inverse relationship of Ki67 levels with ER and PR, while values were directly proportional to the tumorgrade and Her2/neu status. No significant association was found between Ki67 and size of tumor or nodal status. Ki67immunoexpression may offer an independent predictive tumor marker and for routine application in cases of breast cancer.     

Erythropoietin and its receptor in breast cancer: correlation with steroid receptors and outcome.

Autocrine/paracrine erythropoietin (EPO) action, promoting cell survival and mediated by its receptor (EPOR) in various solid tumors, including breast carcinoma, questions about the prognostic and therapeutic interest of this system. The expression of EPO/EPOR is steroid dependent in some tissues; however, a clear relationship of EPO/EPOR and steroid receptors in breast cancer has not been established thus far. Recently, the field of steroid receptors has expanded, including rapid effects mediated by membrane-associated receptors, regulating cell survival or apoptosis. The aim of this study was to evaluate EPO/EPOR and membrane-associated steroid receptor expression in breast carcinoma, in view of their prognostic significance, compared with other established markers [estrogen receptor (ER)-progesterone receptor (PR) status and Her2 expression] and hypoxia-induced factor 1 nuclear localization in 61 breast cancer specimens followed for 相似文献   

Androgen receptor (AR) expression in 400 breast carcinomas: is routine AR assessment justified?

Background: Triple negative breast carcinomas (TNBC) do not benefit from hormonal or Herceptin therapies. In search of novel therapeutic targets for TNBC, interest is escalating in a subset of these tumors that are androgen receptor (AR) positive with potential benefit from anti-androgen therapy. Against this background, the frequency of AR expression alone and in combination with other markers and morphologic features was assessed to identify TNBC subtypes for targeted therapy. Methods: 400 consecutive invasive mammary carcinomas with known estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and HER2 status were selected for study. The frequency of AR positivity alone or in combination with other markers was recorded with specific attention to the morphology of AR+ TNBCs. Ki67 was evaluated in selected group of cases. ASCO/CAP guidelines were used for interpretation of the various biomarkers. Results: Of the 400 tumors, 32 (8%) carcinomas were quadruple negative (ER-, PR-, AR-, Her2-), while 50 tumors (12.5%) were triple negative (ER-, PR-, Her2-); 18 (36%) of the triple negative tumors were AR positive and 10 (55%) of these were classic apocrine carcinomas. Fourteen cases, all apocrine carcinomas, were AR and Her2 positive. All 32 QN carcinomas were poorly differentiated and they had the highest Ki67 labeling index. Conclusion: The relatively high proportion of AR+ tumors (36%) among the 50 triple negative carcinomas is an important finding in support of routine assessment of AR in at least all TNBCs and apocrine carcinomas as a potential target for therapy.     

三阴性乳腺癌的临床特点与治疗

三阴性乳腺癌(TNBC)是乳腺癌的特殊亚型,细胞缺乏雌激素受体(ER)、孕激素受体(PH)和人表皮生长因子受体-2(HER-2),其临床特点及预后不同于其他类型乳腺癌,是近年来乳腺癌研究领域的一大热点.     

Comedo-DCIS is a precursor lesion for basal-like breast carcinoma: identification of a novel p63/Her2/neu expressing subgroup

Basal breast cancer comprises ~15% of invasive ductal breast cancers, and presents as high-grade lesions with aggressive clinical behavior. Basal breast carcinomas express p63 and cytokeratin 5 (CK5) antigens characteristic of the myoepithelial lineage, and typically lack Her2/neu and hormone receptor expression. However, there is limited data about the precursor lesions from which they emerge. Here we wished to determine whether comedo-ductal carcinoma in situ (comedo-DCIS), a high-risk in situ breast lesion, serve as precursors for basal-like breast cancer. To determine this link, p63, CK5, Her2/neu, epidermal growth factor receptor (EGFR), estrogen receptor (ER) and progesterone receptor (PgR) expression were analyzed by immunohistochemistry in 17 clinical comedo- and 12 noncomedo-DCIS cases, and in tumors derived from unfractionated and CK5-overexpressing subpopulation (MCF10DCIS.com-CK5^high) of MCF10DCIS.com cells, a model representative of clinical comedo-DCIS. p63 and Her2/neu coexpression was analyzed by immunofluorescence double labeling. A novel p63/CK5/Her2/neu expressing subpopulation of cells that are ER⁻/PgR⁻/EGFR⁻ were identified in the myoepithelial and luminal areas of clinical comedo-DCIS and tumors derived from unfractionated MCF10DCIS.com and MCF10DCIS.com-CK5^high cells. These data suggest that p63 and Her2/neu expressors may share a common precursor intermediate. P63, but not Her2/neu, expression was significantly associated (P = 0.038) with microinvasion/recurrence of clinical comedo-DCIS, and simultaneous expression of p63 and Her2/neu was marginally associated (P = 0.067) with comedo-DCIS. These data suggest that p63/Her2/neu expressing precursor intermediate in comedo-DCIS may provide a cellular basis for emergence of p63+/Her2/neu- or p63+/Her2/neu+ basal-like breast cancer, and that p63/Her2/neu coexpression may serve as biomarkers for identification of this subgroup of basal-like breast cancers.     

BRCA1 germline mutation in a woman with metaplastic squamous cell breast cancer

BACKGROUND: Breast cancers arising in women with germline BRCA1 mutations are most likely to be estrogen receptor (ER), progesterone receptor (PR), and HER2/neu negative (so-called triple negative or basal-like breast cancers). Metaplastic carcinoma with pure squamous differentiation is a very rare histological subtype (0.1% of all breast cancers) and is usually ER, PR, and HER2/neu negative by immunohistochemistry. A BRCA1 germline mutation in squamous cell breast cancer has never been reported. CASE REPORT: A 25-year-old woman was diagnosed with squamous cell cancer of the breast. Three years later, she developed contralateral breast cancer, also of the squamous cell subtype. Both tumors were triple negative. Because of the patient's history and her strong family history, genetic testing was recommended. The patient was found to be carrier of a BRCA1 germline mutation. CONCLUSION: We report, to our knowledge, the first case of a BRCA1 mutation in a woman with metaplastic squamous cell breast cancer.     

Estrogen receptor alpha and beta, progesterone receptor, pS2 and HER-2/neu expression delineate different subgroups in ductal carcinoma in situ of the breast

Antiestrogen therapy of ductal carcinoma in situ (DCIS) has become a more common option in reducing risk of developing invasive cancer. Previously, estrogen receptor alpha (ER-alpha) was evaluated as the only predictive factor. Immunohistochemical staining was performed for ER-alpha, estrogen receptor ER-beta, progesterone receptor (PR), pS2 and her-2/neu in 59 cases of ductal carcinoma in situ (DCIS). We observed a positive correlation between the expression of ER-alpha (p=0.003), PR (p<0.001) and histopathological grading. Of the DCIS, 61.5% of ER-beta positive (p=0.046) and 35.5% of PR positive samples showed a coexpression with pS2, whereas 72.1% of pS2 negative DCIS were also negative for ER-beta and 92.9% of PR negative DCIS were negative for pS2 (p=0.012). In contrast, 50.0% of her-2/neu negative DCIS expressed ER-beta receptor (p=0.052). We propose that there are subpopulations of DCIS which can be described by distinct endocrine-associated expression patterns.     

MicroRNAs as regulatory elements in triple negative breast cancer

Triple negative breast cancer is a very aggressive subtype of breast cancer characterized by high recurrence rates and a greater likelihood of death compared to other breast cancers. Additionally, it is characterized by lack of expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2)/neu. The current treatment for triple negative breast cancer is chemotherapy and that often results in a poor outcome. Therefore, it is essential that new, alternative therapeutic targets are identified. MicroRNAs are small non-coding elements that regulate the expression of various genes. Research has identified microRNAs promoting and in some cases suppressing cell proliferation by targeting genes in triple negative breast cancer cells. Thus, they are promising cancer targets and they should be further investigated as they could function as biomarkers of triple negative breast cancer in the future. Here we focus on the role of microRNAs in triple negative breast cancer and their potential as therapeutic targets.     

Steroid hormone receptor status of mouse mammary stem cells

The estrogen receptor alpha (ERalpha), progesterone receptor (PR), and erbB2 (Her2 in humans) are important prognostic markers of human breast cancer, and they are variably expressed in different subtypes of breast cancer. The basal subtype, for example, is negative for ERalpha, PR, and Her2 by immunohistochemistry. We investigated the expression of these signaling molecules in enriched populations of mouse mammary stem cells and luminal cells that were isolated according to their differential expression of CD24 and the alpha6beta1-integrin complex. We found that the basal population, which is enriched in mouse mammary stem cells, did not express ERalpha, PR, or ErbB2/Her2 but did express epidermal growth factor receptor (EGFR)/ErbB1, whereas the subset of cells enriched for luminal cells expressed ERalpha (37% of cells) and PR (40% of cells) but not ErbB2/Her2 or EGFR/ErbB1. Ovariectomy confirmed the importance of estrogen signaling to luminal cell proliferation but had no effect on the size of the mouse mammary stem cell-enriched population. Thus, mouse mammary stem cells were negative for ERalpha, PR, and ErbB2 and appeared to share common properties with poor-prognosis basal breast cancer.     

The role of histopathologic testing on apocrine carcinoma of the breast

Background: Apocrine carcinoma is a rare primary breast tumor characterized by the apocrine morphology. The purpose of this article is to report a review of cases with apocrine carcinoma and draw physicians' attention to the benefits of immunphenotypic techniques in cases with suspected apocrine morphology in diagnosing this uncommon breast tumor.Methods: In this study, authors report a case series of 15 cases with apocrine carcinoma from totally 4123 breast cancer cases. Data collected between years 2008 and 2016 from Istanbul School of Medicine department of surgery archive by analyzing surgical approach to cases and immunphenotypic features of tumors according to the date of examining in our pathology department.Results: In this study, Androgen, “gross cystic disease fluid protein-15” (GCDFP-15), estrogen (ER), progesterone (PR) and Her-2 neu receptor status supported evidence of apocrine carcinoma has been reviewed. As a result, HER-2 neu, GCDFP-15, androgen receptor positivity in general are useful in the diagnosis of apocrine carcinoma. In addition of these data our study revealed that GCDFP-15 positive patients are more prone to have local recurrence and distant metastases.Conclusions: We briefly describe and discuss the molecular features and new diagnostic biomarkers for this rare mammary malignancy. The importance of comprehensive profiling is highlighted due to synergistic and potentially antagonistic molecular events in the individual patients.     

Small cell carcinoma of the breast

Small cell carcinoma of the breast (SCCB) is an uncommon neoplasm that accounts for less than 1% of primary breast cancers. Histologically, these tumors have striking similarities to small call carcinoma of the lung, usually with evidence of associated ductal carcinoma-in-situ (DCIS) with areas of ductal, lobular, or papillary differentiation. Immunoreactivity for neuroendocrine markers is documented in two thirds of cases, while 33% to 50% are positive for estrogen receptor (ER) or progesterone receptor (PR). Her2/neu expression has not been reported in SCCB. Treatment, which may include surgery, radiotherapy, and combination chemotherapy, is based on clinical stage and the presence of metastases. Prognosis is variable and is dependent on the initial stage of disease.     

Correlation of Hormone Receptor and HER2/neu Expression with Clinicopathologic Parameters in Primary Breast Tumors

Background: Breast cancer (BC) is a major health issue worldwide as well as in Pakistan. All women belonging to any race, ethnicity or lineage are in danger of developing breast cancer. Significant factors influencing the development of breast malignancies are the genetic background, environmental conditions, reproductive parameters, the consequences of female hormones both intrinsic and extrinsic, alteration of immune status, and biologic determinants. Materials and Methods: Overall 150 biopsy proven patients were included in the study. Samples were submitted for histopathology and determination of estrogen and progesterone receptor expression and HER2/neu status. Associations with other characteristics like age, tumor stage, node involvement, histological grade were also studied. Results: Mean age at presentation was 46.7 years. The majority had invasive ductal carcinoma, 100 (84.7%), and were in stage pT3, 54 (45.7%). Important relationships (P<0.05) were found among ER, PR positivity, and Her 2 neu overexpression. However, no noteworthy link was identified amongst ER, PR, Her 2 neu and tumor grade, stage, age, lymph node involvement except for the menopausal status. Conclusions: In summary, breast cancer patients featured an advanced stage of disease, more lymph node involvement, and moderately high grade tumors and with more estrogen, progesterone receptor and HER2 positive tumors.     

High HSP90 expression is associated with decreased survival in breast cancer

The heat shock protein HSP90 chaperones proteins implicated in breast cancer progression, including Her2/neu. HSP90-targeting agents are in clinical trials for breast cancer. HSP90 expression is high in breast cancer cell lines, yet no large studies have been conducted on expression in human tumors and the association with clinical/pathologic variables. Tissue microarrays containing 10 cell lines and primary specimens from 655 patients with 10-year follow-up were assessed using our automated quantitative analysis (AQUA) method; we used cytokeratin to define pixels as breast cancer (tumor mask) within the array spot and measured HSP90 expression within the mask using Cy5-conjugated antibodies. We similarly assessed estrogen receptor, progesterone receptor, and Her2/neu expression. HSP90 expression was more variable in human tumors than in cell lines (P < 0.0001). High HSP90 expression was associated with decreased survival (P = 0.0024). On multivariable analysis, high HSP90 expression remained an independent prognostic marker. High HSP90 expression was associated with high Her2/neu and estrogen receptor, large tumors, high nuclear grade, and lymph node involvement. Although HSP90 levels were high in all our cell lines, expression in tumors was more variable. High HSP90 expression in primary breast cancer defines a population of patients with decreased survival. Evaluation of HSP90 expression in early-stage breast cancer may identify a subset of patients requiring more aggressive or pathway-targeted treatment. Prospective studies are needed to confirm the prognostic role of HSP90, as well as the predictive role of HSP90 expression in patients treated with HSP90 inhibitors.     

Immunohistochemical Profile of Breast Cancer Patients at a Tertiary Care Hospital in New Delhi,India

Background: To assess the immunohistochemical expression of estrogen receptor (ER), progesterone receptor(PgR) and human epidermal growth factor receptor-2 (HER2) neu receptor in breast cancer and their associationswith various clinicopathological characteristics. Materials and Methods: This is a retrospective analysis of womenwho presented with primary, unilateral breast cancer in the Department of Medical Oncology at Rajiv GandhiCancer Institute and Research Centre, Delhi, India during the period from January 2008 to December 2011. Datawere retrieved from the medical records of the hospital including both early and locally advanced cancer cases.ER, PgR and HER2neu expression in these patients was assessed and triple negative patients were identified.Associations of triple negative and non-triple negative groups with clinicopathological characteristics were alsoevaluated. Results: A total of 1,284 women (mean age 52.1 years, 41.9% premenopausal) were included in theanalysis. Hormone receptor positivity (ER and/or PgR) was seen in 63.4% patients, while 23.8% of tumors weretriple negative. Only 23.0% were HER2 positive. Around 10.0% of tumors were both ER and HER2 positive.ER and PgR positivity was significantly associated with negative HER2 status (p-value <0.0001). Younger age,premenopausal status, higher tumor grade, lymph node negativity, advanced cancer stage, and type of tumorwere strongly associated with triple negativity. Significantly, a smaller proportion of women had ductal carcinomain situ in the triple negative group compared with the non-triple negative group (35.6% versus 60.8%, p-value<0.01). Conclusions: The present analysis is one of the largest studies from India. The majority of the Indianbreast cancer patients seen in our hospital present with ER and PgR positive tumors. The triple negative patientstended to be younger, premenopausal, and were associated with higher tumor grades, negative lymph nodesstatus and lower frequency of ductal carcinoma in situ.