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Molecular & Cellular Proteomics 7:1795-1809, 2008.
© 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

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

Julio E. Celis^,,¶, Pavel Gromov^,, Teresa Cabezón^,, José M. A. Moreira^,, Esbern Friis^,||, Karin Jirström^**, Antonio Llombart-Bosch, Vera Timmermans-Wielenga^,, Fritz Rank^, and Irina Gromova^,

From the Department of Proteomics in Cancer, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark, ^|| Department of Breast and Endocrine Surgery and Department of Pathology, the Centre of Diagnostic Investigations, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark, ^** Center for Molecular Pathology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, 205 02 Malmö, Sweden, Department of Pathology, University of Valencia and Instituto Valenciano de Oncologia, 46010 Valencia, Spain, and Danish Centre for Translational Breast Cancer Research (DCTB), Strandboulevarden 49, DK-2100 Copenhagen, Denmark

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.

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