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

Sami Shousha,Taneisha Mcfarlane,Oliver Anscombe

doi:10.1007/s12253-019-00662-9

Sami Shousha, Taneisha Mcfarlane + Show 1 more

Open Access

https://doi.org/10.1007/s12253-019-00662-9

Copy DOI

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 over-expression of claudin 1 and 3 may have therapeutic implications as targets for managing apocrine cancers.

Highlights

The claudins are a family of small transmembrane proteins that constitute the integral proteins of the tight junctions between epithelial cells that maintain cellular polarity, mediate permeability and are involved in signalling between the cells and their environment [1, 2]
To the best of our knowledge, this is the first study of claudins in a wide range of apocrine breast lesions
We found a consistent expression pattern from benign to invasive carcinoma

Summary

Introduction

The claudins are a family of small transmembrane proteins that constitute the integral proteins of the tight junctions between epithelial cells that maintain cellular polarity, mediate permeability and are involved in signalling between the cells and their environment [1, 2]. Most tissues or cell types express multiple claudins which are specific for a given tissue or cell [1]. Altered expression of several claudins, in particular claudin 1, 3, 4 and 7 has been linked to the development of various cancers [1], and are thought to be implicated in the metastatic process [3]. The. alteration can be in the form of over-expression or down regulation depending on the type of cancer [4]. Claudin 1, 3 and 4 were detected by immunohistochemistry in the membranes of the majority of normal duct cells [5]. To the best of our knowledge, claudin expression in other apocrine breast lesions has not been reported

Objectives

Methods

Findings

Conclusion