All Benign and Malignant Apocrine Breast Lesions Over-Express Claudin 1 and 3 and Are Negative for Claudin 4

Abstract

Invasive apocrine carcinoma of the breast is an uncommon triple negative tumour that lacks a specific therapeutic target. Apocrine metaplasia of the breast shares common morphological features with apocrine carcinoma, and was previously found to consistently over-express claudin 1 and to lack claudin 4. This study was aimed at finding whether apocrine carcinoma, and other related apocrine breast lesions, have similar claudin profile. The immunohistochemical expression of claudin 1, 3 and 4 was studied in 11 cases of in situ and invasive apocrine breast carcinoma, 7 benign apocrine lesions and 45 consecutive morphologically non-apocrine triple negative breast carcinomas. All cases were also immunostained for Gross Cystic Disease Fluid Protein-15 (GCDFP-15), a marker for apocrine differentiation. Apocrine breast lesions maintained their expression pattern from benign through DCIS to invasive carcinoma; all showing strong expression of claudin 1 and 3 and absence of claudin 4. The same pattern of expression was seen in 2 out of the 45 morphologically non-apocrine tumours, but both showed strong positive staining for GCDFP-15. It is concluded that all benign and malignant apocrine lesions of the breast have a consistent pattern of claudin 1, 3 and 4 expression, suggesting the presence of a specific pathway for the development of invasive apocrine carcinoma. The overexpression of claudin 1 and 3 may have therapeutic implications as targets for managing apocrine cancers.

An Update on the Molecular and Clinical Characteristics of Apocrine Carcinoma of the Breast

“…39 Sousha et al recently demonstrated claudin 1 and claudin 3 expressions and the lack of claudin 4 protein expression in a small cohort of apocrine lesions, including invasive apocrine carcinoma with the triple-negative phenotype. 40 The diagnostic and potential therapeutic utility of these findings remains unknown.…”