Apocrine differentiation in human mammary carcinoma

Mossler, Jeffrey A.; Barton, Thomas K.; Brinkhous, A. D.; McCarty, Kenneth S.; Moylan, Joseph A.

doi:10.1002/1097-0142(19801201)46:11<2463::aid-cncr2820461127>3.0.co;2-#

Cited by 109 publications

(39 citation statements)

References 15 publications

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“…39 Miller et al 40 explained that breast carcinomas showing apocrine differentiation have high 5a reductase activity, which is capable of metabolizing androgens, and possess androgen receptors. These tumors may have a different endocrine drive.…”

Section: Discussionmentioning

confidence: 99%

Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer

et al. 2014

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Treatment of triple-negative invasive breast cancers, defined by the absence of estrogen and progesterone receptors and c-erbB2 expression, remains challenging. Androgen receptor, a member of the nuclear receptor superfamily that is involved in signaling pathways regulating cell proliferation, has been implicated in breast tumorigenesis. We immunohistochemically examined the expression of androgen receptor, basal markers (CK14, 34bE12) and EGFR in 699 triple-negative invasive breast cancers in tissue microarrays using the streptavidin-biotin method, and correlated the findings with clinical outcome. Positive androgen receptor expression was defined as staining of 1% or more of tumor cell nuclei. Survival outcomes were estimated with the Kaplan-Meier method and compared between groups with log-rank statistics. Cox proportional hazards models were used to determine the effect of androgen receptor on survival outcomes. Immunohistochemical positivity was observed in 38% of tumors, with the proportion of stained tumor cells ranging from 1 to 95% (mean 29%, median 10%). Androgen receptor expression was inversely associated with histologic grade and mitotic score. CK14, 34bE12 and EGFR confirmed 85% of cases to be basal-like, without significant association of basal-like phenotype with androgen receptor expression. Disease-free survival was significantly better in androgen receptor-positive triple-negative breast cancer, with a trend for improved overall survival. Decreased recurrence likelihood in both triple-negative and basal-like tumors (hazard ratio, 0.704; 95% confidence intervals, 0.498-0.994; P ¼ 0.0464; and hazard ratio, 0.675; 95% confidence intervals, 0.468-0.974; P ¼ 0.0355, respectively) was noted within 5 years of diagnosis but not thereafter. Our study suggests that loss of androgen receptor in triple-negative breast cancers augurs a worse prognosis, including those with basal-like features. More work in elucidating its relationship with mechanisms of progression, as well as trials of targeted treatment for androgen receptor-expressing triple-negative tumors, needs to be performed.

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Section: Discussionmentioning

confidence: 99%

Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer

et al. 2014

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“…Molecular apocrine carcinomas encompass tumors that share some common expression characteristics with the ERBB2 class (ER␣ Ϫ /PgR Ϫ /ERBB2 ϩ ) in the Stanford classification as well as with some lesions that exhibit morphological features of the triple negative group (high grade lesions; ER␣ Ϫ /PgR Ϫ /ERBB2 Ϫ ). Invasive apocrine carcinomas (IACs) as defined by morphological features correspond to 0.5-3% of all invasive ductal carcinomas (IDCs) (7)(8)(9)(10), and despite the fact that they are histologically distinct from other breast lesions there are currently no standard molecular criteria available for their diagnosis and no precise information as to their prognosis (Refs. 10 -14 and references therein).…”

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confidence: 99%

“…10 -14 and references therein). IACs are generally considered as a variant of IDC (8,10,15), although Japaze et al (11) recently defined separate histopathological criteria for the diagnosis of pure IACs, which have a less aggressive behavior than IDC-NST. The identification of apocrine carcinomas is further complicated by the fact that some of the less differentiated carcinomas may actually represent apocrine carcinomas that have lost their apocrine morphological characteristics, making it difficult to distinguish them from IDC-NST using purely morphological criteria (16,17).…”

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confidence: 99%

15-Prostaglandin Dehydrogenase Expression Alone or in Combination with ACSM1 Defines a Subgroup of the Apocrine Molecular Subtype of Breast Carcinoma

Celis

Gromov

Cabezón

et al. 2008

Molecular & Cellular Proteomics

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Established histopathological criteria divide invasive breast carcinomas into defined groups. Ductal of no specific type and lobular are the two major subtypes accounting for around 75 and 15% of all cases, respectively. The remaining 10% include rarer types such as tubular, cribriform, mucinous, papillary, medullary, metaplastic, and apocrine breast carcinomas. Molecular profiling technologies, on the other hand, subdivide breast tumors into five subtypes, basal-like, luminal A, luminal B, normal breast tissue-like, and ERBB2-positive, that have different prognostic characteristics. An additional subclass termed "molecular apocrine" has recently been described, but these lesions did not exhibit all the histopathological features of classical invasive apocrine carcinomas (IACs). IACs make up 0.5-3% of the invasive ductal carcinomas, and despite the fact that they are morphologically distinct from other breast lesions, there are presently no standard molecular criteria available for their diagnosis and as a result no precise information as to their prognosis. Toward this goal our laboratories have embarked in a systematic proteomics endeavor aimed at identifying biomarkers that may characterize and subtype these lesions as well as targets that may lead to the development of novel targeted therapies and chemoprevention strategies. By comparing the protein expression profiles of apocrine macrocysts and non-malignant breast epithelial tissue we have previously reported the identification of a few proteins that are specifically expressed by benign apocrine lesions as well as by the few IACs that were available to us at the time. Here we reiterate our strategy to reveal apocrine cell markers and present novel data, based on the analysis of a considerably larger number of samples, establishing that IACs correspond to a distinct molecular subtype of breast carcinomas characterized by the expression of 15-prostaglandin dehydrogenase alone or in combination with a novel form of acyl-CoA synthetase medium-chain family member 1 (ACSM1). Moreover we show that 15-prostaglandin dehydrogenase is not expressed by other breast cancer types as determined by gel-based proteomics and immunohistochemistry analysis and that antibodies against this protein can identify IACs in an unbiased manner in a large breast cancer tissue microarray making them potentially useful as a diagnostic aid. Molecular & Cellular Proteomics 7:1795-1809, 2008.Breast cancer is the leading cause of cancer deaths in women today and the most common cancer among women in the Western world (1). According to the World Health Organization more than 1.2 million people will be diagnosed with breast cancer this year worldwide, and the global incidence rates are increasing. In Denmark, ϳ4,200 women were diagnosed with the disease in 2005; this means that the number of new cases diagnosed every year has tripled in the past 40 years. As a result, the lifetime risk of a woman developing breast cancer has increased from 1 in 28 just 50 years ago to 1 in 8 today. The 5-year...

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“…It is a rare histological type; its reported prevalence is 0.4% of all breast cancers (Mossler et al 1980). The prognosis is said to be relatively good compared to other breast cancers (Gădăleanu and Galatâr 1986).…”

Section: Discussionmentioning

confidence: 99%

“…© 2011 Tohoku University Medical Press Apocrine carcinoma of the breast is a rare type of breast cancer. It is estimated to represent 0.4% of all breast cancers (Mossler et al 1980). Many of the cases are diagnosed at stage I or II; thus the prognosis is thought to be better than that for other breast cancers (Gădăleanu and Galatâr 1986).…”

mentioning

confidence: 99%

Incidental Detection of Breast Apocrine Carcinoma via Endometrial Cytology

Shiota

Kotani

Umemoto

et al. 2011

Tohoku J. Exp. Med.

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Breast apocrine carcinoma is a rare malignancy characterized histologically by a predominance of acidophilic tumor cells exhibiting apocrine metaplasia. Apocrine tumors represent only about 0.4% of all breast cancers. Many cases are diagnosed at stage I or II; thus, the prognosis is better than that for other types of breast cancer. Here we present a 57-year-old female patient with primary apocrine breast carcinoma that was incidentally discovered by endometrial cytology. The patient had undergone routine uterine cancer screening at the age of 56 with resulting positive endometrial cytology. Subsequent histological examination of an endometrial biopsy revealed suspected metastatic uterine adenocarcinoma. Further evaluation revealed a 3-cm mass in the left breast, which was histopathologically diagnosed as breast cancer. Dual procedures were performed at the departments of gynecology and breast surgery. The patient underwent a modified radical mastectomy of the left breast and left axillary lymph node dissection. Laparotomy revealed multiple adhesions throughout the peritoneal cavity that suggested invasive metastatic cancer, and a right adnexectomy was performed. Histopathological examination of the resected left breast and right ovary tissues revealed apocrine carcinoma. Thus, stage IV breast cancer was diagnosed. The patient finished 6 cycles of paclitaxel and is now under observation on an outpatient basis. In this patient, breast cancer was discovered incidentally through a detailed work-up after a positive result of endometrial cytology. Uterine cancer screening has the potential, although rare, to detect metastatic cancer originating elsewhere. This should be taken into consideration during the work-up due to positive endometrial cytology.Keywords: apocrine carcinoma; breast cancer; endometrial cytology; metastasis; uterine cancer screening Tohoku J. Exp. Med., 2011, 225 (4), 235-237. © 2011 Tohoku University Medical Press Apocrine carcinoma of the breast is a rare type of breast cancer. It is estimated to represent 0.4% of all breast cancers (Mossler et al. 1980). Many of the cases are diagnosed at stage I or II; thus the prognosis is thought to be better than that for other breast cancers (Gădăleanu and Galatâr 1986). The 10-year survival rate has been reported to be 52% (d'Amore et al. 1988).Metastatic foci of breast cancers are often detected in the lungs, liver, bones, or ovaries. To the best of our knowledge, there has been only one report on breast cancer that was detected from an initial diagnosis of a uterine metastasis, although it was not an apocrine carcinoma of the breast (Kumar and Hart 1982).Here, we report a patient with apocrine carcinoma of the breast with uterine metastasis that was diagnosed through evaluation of the patient because of positive endometrial cytology. PatientA 57-year-old woman, gravid 2 para 2, postmenopausal for 6 years, with no remarkable past medical history or family history, had a diagnosis of negative for intraepithelial lesion or malignancy (NILM) with cervical co...

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Apocrine differentiation in human mammary carcinoma

Cited by 109 publications

References 15 publications

Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer

Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer

15-Prostaglandin Dehydrogenase Expression Alone or in Combination with ACSM1 Defines a Subgroup of the Apocrine Molecular Subtype of Breast Carcinoma

Incidental Detection of Breast Apocrine Carcinoma via Endometrial Cytology

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