Research article
Molecular apocrine differentiation is a common feature of breast cancer in patients with germline PTEN mutations
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* Corresponding author: Michel Longy longy@bergonie.org
1 INSERM U916, Université de Bordeaux, Institut Bergonié, 229 cours de l'Argonne, 33000, Bordeaux, France
2 Tumor Identity Card program (CIT3), Ligue Nationale Contre le Cancer, 12 rue Corvisart, 75013 Paris, France
3 Pathology Department, Institut Bergonié, 229 cours de l'Argonne, 33000, Bordeaux, France
4 Cancer Genetics Unit, Centre Léon Bérard, 28 rue Laennec, 69008 Lyon, France
5 Medical Genetics Unit, CHU de Nantes, 5 allée de l'Île Gloriette, 44000 Nantes, France
6 Cancer Genetics Unit, Centre Eugène Marquis, avenue de la Bataille Flandres-Dunkerque, 35000 Rennes, France
7 Medical Genetics Unit, CHU de Poitiers, 2 rue Milétrie, 86000 Poitiers, France
8 Medical Genetics Unit, CHU d'Angers, rue Larrey, 49100 Angers, France
9 Dermatology Department, CHU de Dijon, 2 boulevard du Maréchal de Lattre de Tassigny, 21000 Dijon, France
10 Dermatology Department, Hôpital Avicenne, 125 rue Stalingrad, 93000 Bobigny, France
11 Cancer Genetics Unit, Institut Bergonié, 229 cours de l'Argonne, 33000 Bordeaux, France
Breast Cancer Research 2010, 12:R63 doi:10.1186/bcr2626
Published: 16 August 2010Abstract
Introduction
Breast carcinoma is the main malignant tumor occurring in patients with Cowden disease, a cancer-prone syndrome caused by germline mutation of the tumor suppressor gene PTEN characterized by the occurrence throughout life of hyperplastic, hamartomatous and malignant growths affecting various organs. The absence of known histological features for breast cancer arising in a PTEN-mutant background prompted us to explore them for potential new markers.
Methods
We first performed a microarray study of three tumors from patients with Cowden disease in the context of a transcriptomic study of 74 familial breast cancers. A subsequent histological and immunohistochemical study including 12 additional cases of Cowden disease breast carcinomas was performed to confirm the microarray data.
Results
Unsupervised clustering of the 74 familial tumors followed the intrinsic gene classification of breast cancer except for a group of five tumors that included the three Cowden tumors. The gene expression profile of the Cowden tumors shows considerable overlap with that of a breast cancer subgroup known as molecular apocrine breast carcinoma, which is suspected to have increased androgenic signaling and shows frequent ERBB2 amplification in sporadic tumors. The histological and immunohistochemical study showed that several cases had apocrine histological features and expressed GGT1, which is a potential new marker for apocrine breast carcinoma.
Conclusions
These data suggest that activation of the ERBB2-PI3K-AKT pathway by loss of PTEN at early stages of tumorigenesis promotes the formation of breast tumors with apocrine features.