Molecular apocrine differentiation is a common feature of breast cancer in patients with germline PTEN mutations. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Breast Cancer Research Year : 2010

Molecular apocrine differentiation is a common feature of breast cancer in patients with germline PTEN mutations.

Mickaël Guedj
  • Function : Author
  • PersonId : 918884
Isabelle de Mascarel
  • Function : Author
  • PersonId : 918886
Valerie Velasco
  • Function : Author
  • PersonId : 918887
Renaud Schiappa
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  • PersonId : 918888
Valérie Bonadona
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  • PersonId : 912531
Olivier Ingster
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  • PersonId : 918890
Pierre Vabres
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  • PersonId : 899466
Frédéric Caux
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  • PersonId : 907535
Aurelien de Reynies
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  • PersonId : 918891

Abstract

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.

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Cancer
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inserm-00663724 , version 1 (27-01-2012)

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Guillaume Banneau, Mickaël Guedj, Gaëtan Macgrogan, Isabelle de Mascarel, Valerie Velasco, et al.. Molecular apocrine differentiation is a common feature of breast cancer in patients with germline PTEN mutations.. Breast Cancer Research, 2010, 12 (4), pp.R63. ⟨10.1186/bcr2626⟩. ⟨inserm-00663724⟩
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