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Zoran Gatalica - One of the best experts on this subject based on the ideXlab platform.
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Apocrine carcinoma of the breast a comprehensive review
Histology and Histopathology, 2013Co-Authors: Semir Vranic, Michael Castro, Fernando Schmitt, Jose Luis Costa, Sandeep K Reddy, Anna Sapino, Zoran GatalicaAbstract:Apocrine carcinoma of the breast is a rare, special type of breast carcinoma showing distinct morphologic, immunohistochemical and molecular genetic features. Apocrine epithelium has a characteristic steroid receptor profile that is estrogen receptor and progesterone receptor negative and androgen receptor positive. This combination of morphologic and immunohistochemical characteristics is essential for the proper recognition of the Apocrine carcinomas. Strictly defined, Apocrine carcinomas express either Her-2/neu or EGFR, which along with androgen receptor positivity make patients with the Apocrine carcinoma eligible for targeted therapies.
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Review Apocrine carcinoma of the breast: A comprehensive review
2013Co-Authors: Semir Vranic, Michael Castro, Fernando Schmitt, Jose Luis Costa, Sandeep K Reddy, Anna Sapino, Zoran GatalicaAbstract:Summary. Apocrine carcinoma of the breast is a rare, special type of breast carcinoma showing distinct morphologic, immunohistochemical and molecular genetic features. Apocrine epithelium has a characteristic steroid receptor profile that is estrogen receptor and progesterone receptor negative and androgen receptor positive. This combination of morphologic and immunohistochemical characteristics is essential for the proper recognition of the Apocrine carcinomas. Strictly defined, Apocrine carcinomas express either Her-2/neu or EGFR, which along with androgen receptor positivity make patients with the Apocrine carcinoma eligible for targeted therapies.
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EGFR and HER-2/neu expression in invasive Apocrine carcinoma of the breast
Modern Pathology, 2010Co-Authors: Semir Vranic, Eduardo Eyzaguirre, Jill Hagenkord, Nurija Bilalovic, Patrick Adegboyega, Juan Palazzo, Ossama Tawfik, Zoran GatalicaAbstract:This study was undertaken to investigate epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2)/neu expression in a cohort of Apocrine carcinomas of the breast with emphasis on the classification of the breast tumors with Apocrine morphology. In total, 55 breast carcinomas morphologically diagnosed as Apocrine were evaluated for the steroid receptor expression profile characteristic of normal Apocrine epithelium (androgen receptor positive/estrogen receptor (ER) negative/progesterone receptor (PR) negative), and for the expression of EGFR and Her-2/neu proteins, and the copy number ratios of the genes EGFR/CEP7 and HER-2/CEP17 . On the basis of the results of steroid receptors expression, 38 (69%) cases were classified as pure Apocrine carcinoma (androgen receptor positive/ER negative/PR negative), whereas 17 (31%) were re-classified as Apocrine-like carcinomas because they did not have the characteristic steroid receptor expression profile. Her-2/neu overexpression was observed in 54% of the cases (57% pure Apocrine carcinomas vs 47% Apocrine-like carcinomas). HER-2/neu gene amplification was demonstrated in 52% of all cases (54% pure Apocrine carcinomas vs 46% Apocrine-like carcinomas). EGFR protein (scores 1 to 3+) was detected in 62% of all cases and was expressed in a higher proportion of pure Apocrine carcinomas than in the Apocrine-like carcinomas group (76 vs 29%, P =0.006). In the pure Apocrine carcinoma group, Her-2/neu and EGFR protein expression were inversely correlated ( P =0.006, r =−0.499). EGFR gene amplification was observed in two pure Apocrine carcinomas and one Apocrine-like carcinoma. Polysomy 7 was commonly present in pure Apocrine carcinomas (61 vs 27% of Apocrine-like carcinomas; P =0.083) and showed a weak positive correlation with EGFR protein expression ( P =0.025, r =0.326). Our study showed that Apocrine breast carcinomas are molecularly diverse group of carcinomas. Strictly defined pure Apocrine carcinomas are either HER-2-overexpressing breast carcinomas or triple-negative breast carcinomas, whereas Apocrine-like carcinomas predominantly belong to the luminal phenotype. Pure Apocrine carcinomas show consistent overexpression of either EGFR or HER-2/neu, which could have significant therapeutic implications.
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Immunohistochemical analysis of Apocrine breast lesions. Consistent over-expression of androgen receptor accompanied by the loss of estrogen and progesterone receptors in Apocrine metaplasia and Apocrine carcinoma in situ.
Pathology research and practice, 1997Co-Authors: Zoran GatalicaAbstract:Apocrine phenotype is observed in a spectrum of breast epithelial lesions spanning from benign metaplasias to Apocrine carcinoma. Apocrine metaplasia is a common finding in fibrocystic change of the female breast. In situ and invasive Apocrine carcinomas are rare variants of ductal carcinoma. All breast Apocrine lesions were shown to be associated with increased androgen hormones metabolism. We have evaluated 10 cases of Apocrine metaplasia, 3 cases of in situ Apocrine carcinoma and 10 cases of invasive Apocrine carcinomas using immunostaining method for steroid hormone receptors (estrogen, progesterone, androgen), p53, bcl-2 and BRST-2. Paraffin embedded tissue and avidin-biotin peroxidase complex system were used. Androgen receptor (AR) expression is consistently increased in all cases of Apocrine metaplasia when compared with surrounding normal, non-Apocrine breast epithelium. This androgen receptor over-expression is accompanied by the loss of immuno-detectable estrogen and progesterone receptor, and also the loss of bcl-2. An identical pattern of immuno-reactivity is seen in in situ Apocrine carcinomas, but it is observed with less frequency in invasive Apocrine carcinomas, which only infrequently express AR as the only steroid hormone receptor.
Yutaka Tsutsumi - One of the best experts on this subject based on the ideXlab platform.
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Apocrine carcinoma as triple negative breast cancer novel definition of Apocrine type carcinoma as estrogen progesterone receptor negative and androgen receptor positive invasive ductal carcinoma
Japanese Journal of Clinical Oncology, 2012Co-Authors: Yutaka TsutsumiAbstract:Objective: Apocrine carcinoma, a subtype of invasive ductal carcinoma of the breast, expresses androgen receptor (AR), but often lacks estrogen receptor (ER) and progesterone receptor (PgR). In the present study, the author immunohistochemically defined Apocrinetype carcinoma as ER2/PgR2/ARþ invasive ductal carcinoma and analyzed the significance of Apocrine-type carcinoma as triple-negative breast cancer. Methods: Four hundred and forty breast cancers from 429 cases were immunostained for estrogen receptor, progesterone receptor, androgen receptor, human epidermal growth factor receptor type 2 (HER2), p53, Ki-67 and epidermal growth factor receptor. The lesions included 58 in situ malignancies (including 13 Apocrine-type lesions) and 325 invasive ductal carcinomas (including 44 Apocrine type). Results: Of 91 estrogen receptor-negative invasive ductal carcinomas, 44 (48%) belonged to Apocrine-type carcinoma, and overexpression of human epidermal growth factor receptor type 2 and p53 was observed in 23 (52%) and 33 (75%), respectively. Histologically, 22 (50%) were categorized as classical Apocrine carcinoma. Among 281 non-Apocrine invasive ductal carcinomas, 30 (11%) were quadruple-negative (ER2/PgR2/AR2/HER22) and 17 (6%) were hormone receptor-negative and human epidermal growth factor receptor type 2-overexpressed. Invasive ductal carcinomas in the triple-negative breast cancer category (n ¼ 51) were divided into triple-negative, androgen receptor-positive (Apocrine, n ¼ 21) and quadruple-negative (non-Apocrine, n ¼ 30). p53 overexpression was more often seen in the Apocrine-type triple-negative breast cancer (18/21 ¼ 86%) than in the non-Apocrine type (14/30 ¼ 46%) (P , 0.05). Ki-67 labeling was significantly higher in the non-Apocrine type (58%) than in the Apocrine type (37%) (P , 0.01). Epidermal growth factor receptor is consistently expressed in triple-negative breast cancers (16/16 ¼ 100% in Apocrine and 18/20 ¼ 90% in non-Apocrine). Conclusions: Androgen receptor should be added to immunohistochemical panels, since Apocrine-type invasive ductal carcinoma, resembling basal-like phenotypes, may show clinical behaviors different from the basal-like triple-negative breast cancer.
Kristen A. Atkins - One of the best experts on this subject based on the ideXlab platform.
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Pure Apocrine Carcinomas Represent a Clinicopathologically Distinct Androgen Receptor-Positive Subset of Triple-Negative Breast Cancers.
The American Journal of Surgical Pathology, 2016Co-Authors: Anne M. Mills, Kristen A. AtkinsAbstract:Apocrine carcinomas comprise ∼1% of all breast cancers and are characterized by large cells bearing abundant eosinophilic granular cytoplasm, round nuclei, and prominent nucleoli. They are typically estrogen receptor/progesterone receptor/HER2 negative, making them unresponsive to typical hormonal or HER2-based chemotherapy. However, this subtype of triple-negative breast cancers expresses androgen receptor (AR), a feature not shared by most nonApocrine triple-negative cancers (NA-TNCs). AR therefore represents a potential diagnostic tool and therapeutic target for Apocrine breast carcinoma. All pure Apocrine carcinomas diagnosed during a 10-year period were reviewed, and clinicopathologic characteristics were compared with a control group of 26 NA-TNC cases. Twenty Apocrine carcinomas were identified (∼0.8% of all breast cancers). The mean age at diagnosis was 69.3 years for Apocrine carcinomas and 56.7 years for NA-TNC. All Apocrine carcinomas and no NA-TNC were AR positive. The proportions of Apocrine carcinoma grades varied, with G1 being seen in 15% of patients, G2 in 55%, and G3 in 30%. In contrast, 100% of NA-TNC cases were G3. The majority of Apocrine carcinomas presented at low T stage (T1: 70%; T2: 20%; T3: 10%; T4: 0%), whereas NA-TNC cases more often presented at T2 or higher (T1: 46.2%; T2: 30.8%; T3: 11.5%; T4: 11.5%). Thirty percent of Apocrine carcinomas and 30.8% of NA-TNCs had nodal metastases at presentation. Apocrine carcinomas had a favorable clinical prognosis, with 80% of patients showing no evidence of disease-related morbidity or mortality (mean follow-up: 45.2 mo). Pure Apocrine carcinomas represent a clinicopathologically distinct subgroup of triple-negative breast cancer characterized by AR positivity. When compared with NA-TNC, Apocrine carcinomas more often present in older women with lower grade and T stage, a group in which a more conservative treatment regimen is often desired.
Anne M. Mills - One of the best experts on this subject based on the ideXlab platform.
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Pure Apocrine Carcinomas Represent a Clinicopathologically Distinct Androgen Receptor-Positive Subset of Triple-Negative Breast Cancers.
The American Journal of Surgical Pathology, 2016Co-Authors: Anne M. Mills, Kristen A. AtkinsAbstract:Apocrine carcinomas comprise ∼1% of all breast cancers and are characterized by large cells bearing abundant eosinophilic granular cytoplasm, round nuclei, and prominent nucleoli. They are typically estrogen receptor/progesterone receptor/HER2 negative, making them unresponsive to typical hormonal or HER2-based chemotherapy. However, this subtype of triple-negative breast cancers expresses androgen receptor (AR), a feature not shared by most nonApocrine triple-negative cancers (NA-TNCs). AR therefore represents a potential diagnostic tool and therapeutic target for Apocrine breast carcinoma. All pure Apocrine carcinomas diagnosed during a 10-year period were reviewed, and clinicopathologic characteristics were compared with a control group of 26 NA-TNC cases. Twenty Apocrine carcinomas were identified (∼0.8% of all breast cancers). The mean age at diagnosis was 69.3 years for Apocrine carcinomas and 56.7 years for NA-TNC. All Apocrine carcinomas and no NA-TNC were AR positive. The proportions of Apocrine carcinoma grades varied, with G1 being seen in 15% of patients, G2 in 55%, and G3 in 30%. In contrast, 100% of NA-TNC cases were G3. The majority of Apocrine carcinomas presented at low T stage (T1: 70%; T2: 20%; T3: 10%; T4: 0%), whereas NA-TNC cases more often presented at T2 or higher (T1: 46.2%; T2: 30.8%; T3: 11.5%; T4: 11.5%). Thirty percent of Apocrine carcinomas and 30.8% of NA-TNCs had nodal metastases at presentation. Apocrine carcinomas had a favorable clinical prognosis, with 80% of patients showing no evidence of disease-related morbidity or mortality (mean follow-up: 45.2 mo). Pure Apocrine carcinomas represent a clinicopathologically distinct subgroup of triple-negative breast cancer characterized by AR positivity. When compared with NA-TNC, Apocrine carcinomas more often present in older women with lower grade and T stage, a group in which a more conservative treatment regimen is often desired.
Naoko Honma - One of the best experts on this subject based on the ideXlab platform.
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fabp7 and hmgcs2 are novel protein markers for Apocrine differentiation categorizing Apocrine carcinoma of the breast
PLOS ONE, 2014Co-Authors: Pavel Gromov, José M. A. Moreira, Jaime A Espinoza, Majlis Moller Talman, Naoko Honma, Niels Kroman, Vera Timmermans Wielenga, Irina GromovaAbstract:Apocrine carcinoma of the breast is a distinctive malignancy with unique morphological and molecular features, generally characterized by being negative for estrogen and progesterone receptors, and thus not electable for endocrine therapy. Despite the fact that they are morphologically distinct from other breast lesions, no standard molecular criteria are currently available for their diagnosis. Using gel-based proteomics in combination with mass spectrometry and immunohistochemistry we have identified two novel markers, HMGCS2 and FABP7 that categorize the entire breast Apocrine differentiation spectrum from benign metaplasia and cysts to invasive stages. Expression of HMGCS2 and FABP7 is strongly associated with Apocrine differentiation; their expression is retained by most invasive Apocrine carcinomas (IAC) showing positive immunoreactivity in 100% and 78% of Apocrine carcinomas, respectively, as compared to non-Apocrine tumors (16.7% and 6.8%). The nuclear localization of FABP7 in tumor cells was shown to be associated with more aggressive stages of Apocrine carcinomas. In addition, when added to the panel of Apocrine biomarkers previously reported by our group: 15-PGDH, HMGCR and ACSM1, together they provide a signature that may represent a golden molecular standard for defining the Apocrine phenotype in the breast. Moreover, we show that combining HMGCS2 to the steroidal profile (HMGCS2+/Androgen Receptor (AR)+/Estrogen Receptor(ER)-/Progesteron Receptor (PR)- identifies IACs with a greater sensitivity (79%) as compared with the steroidal profile (AR+/ER-/PR-) alone (54%). We have also presented a detailed immunohistochemical analysis of breast Apocrine lesions with a panel of antibodies against proteins which correspond to 10 genes selected from published transcriptomic signatures that currently characterize molecular Apocrine subtype and shown that except for melanophilin that is overexpressed in benign Apocrine lesions, these proteins were not specific for morphological Apocrine differentiation in breast.
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Expression of oestrogen receptor-β in Apocrine carcinomas of the breast
Histopathology, 2007Co-Authors: Naoko Honma, Kaiyo Takubo, Tomio Arai, Fujio Kasumi, Futoshi Akiyama, Motoji Sawabe, Takayuki Hosoi, Noriko Yoshimura, Nobuhiro Harada, Mamoun YounesAbstract:Aims: Apocrine carcinoma of the breast seldom expresses oestrogen receptors (ER) or progesterone receptors (PR), but frequently expresses androgen receptors (AR). Because of this unusual hormone receptor status, it has been suggested that oestrogens have a less important role in the pathogenesis of Apocrine carcinoma. The ER status of Apocrine carcinoma has been studied for one kind of ER, the classic receptor now named ER-α; however, the status of ER-β, a secondary oestrogen receptor, has not been examined systematically in Apocrine carcinoma. The aim was to study ER-β status in Apocrine carcinoma. Methods and results: The expression of ER-β was examined immunohistochemically in 48 Apocrine carcinomas and compared with clinicopathological factors and ER-α, PR and AR status. ER-β positivity was observed in 35 cases (73%), regardless of any clinicopathological factors or the status of other receptors. The results of ER-β mRNA analysis supported the immunohistochemical results. Conclusions: The significance of oestrogens in Apocrine carcinoma should not be dismissed at present when the role of ER-β remains to be determined. Studying the action of oestrogen or antioestrogen in Apocrine carcinoma may reveal a role for ER-β independent of ER-α and raise the potential of hormonal therapy for these tumours.
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comparative study of monoclonal antibody b72 3 and gross cystic disease fluid protein 15 as markers of Apocrine carcinoma of the breast
Apmis, 2006Co-Authors: Naoko Honma, Kaiyo Takubo, Tomio Arai, Mamoun Younes, Fujio Kasumi, Futoshi Akiyama, Goi SakamotoAbstract:Gross cystic disease fluid protein-15 (GCDFP-15) is a commonly used Apocrine marker; however, its expression was recently found to decrease in infiltrating, larger, or metastasizing Apocrine carcinomas of the breast. In the breast, monoclonal antibody (MAb) B72.3 has been reported to be useful as an Apocrine marker although it is used for that purpose much less frequently than GCDFP-15. In the search for a more consistent Apocrine marker, immunoreactivity for MAb B72.3 was examined in Apocrine carcinomas at different stages and compared with GCDFP-15. 47 of 51 Apocrine carcinomas (92%) and 9 of 62 ordinary carcinomas (15%) were MAb B72.3 positive, while 39 of 51 Apocrine carcinomas (76%) and 13 of 62 ordinary carcinomas (21%) were GCDFP-15 positive. Thus, both sensitivity and specificity were higher for MAb B72.3. Furthermore, unlike GCDFP-15, MAb B72.3 exhibited positivity irrespective of infiltrating status, tumor size, or metastatic status. There was no correlation between MAb B72.3-immunoreactivity and GCDFP-15-expression. The combined usage of MAb B72.3 with GCDFP-15 was useful to confirm the diagnosis of Apocrine carcinoma, especially for advanced tumors, with only two cases being negative for both MAb B72.3 and GCDFP-15. Whether these two cases should be differentiated from ordinary Apocrine carcinomas remains to be investigated.
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Expression of GCDFP-15 and AR decreases in larger or node-positive Apocrine carcinomas of the breast
Histopathology, 2005Co-Authors: Naoko Honma, Kaiyo Takubo, Tomio Arai, Mamoun Younes, Fujio Kasumi, Futoshi Akiyama, Motoji Sawabe, Goi SakamotoAbstract:Aims : Apocrine carcinoma of the breast is typically, though not always, positive for gross cystic disease fluid protein-15 (GCDFP-15). In order to clarify the clinical significance of GCDFP-15 in Apocrine carcinomas, GCDFP-15 expression was examined in Apocrine carcinomas of different stages and compared with clinicopathological factors. Apocrine lesions reportedly exhibit an unusual immunohistochemical status, expressing androgen receptors (AR) instead of oestrogen receptors (ER), progesterone receptors (PR), or bcl-2. Their expression was also examined. Methods and results : Fifty-two Apocrine carcinomas were examined immunohistochemically. Thirty-nine (75%) and 29 (56%) were positive for GCDFP-15 and AR, respectively. GCDFP-15 positivity was significantly lower in infiltrating carcinomas than intraductal carcinomas (P = 0.0111). In infiltrating carcinomas, GCDFP-15 positivity was significantly low in tumours ≥ 15 mm (P = 0.0005) and node-positive tumours (P = 0.0004). Similar phenomena were observed for AR. Rare cases were positive for ER (3.8%), PR (5.8%), and bcl-2 (1.9%). Conclusions : GCDFP-15 positivity is transient and should not be considered a definitive marker of Apocrine carcinomas. Cases which have Apocrine features but lack GCDFP-15 expression should rather be considered as advanced Apocrine carcinomas. ER/PR/bcl-2 negativity will sometimes be helpful to confirm the diagnosis of Apocrine carcinoma, because it is more consistent than GCDFP-15/AR positivity.