title: Claudin 4 expression in triple-negative breast cancer: correlation with androgen receptors and Ki-67 expression.
abstract: Breast cancer is the most common malignancy in women and the leading cause of cancer mortality worldwide. Triple-negative breast cancer (TNBC) is an important phenotype of breast cancer that accounts for a relatively small number of breast cancer cases but still represent a focus of increasing interest at the clinical, biological, and epidemiological level. Claudins are the major component of the tight junction, and only a few studies have addressed the role of claudins in breast cancer, especially TNBC. Androgen receptors (ARs), as members of the nuclear receptor superfamily, are known to be involved in a complex network of signaling pathways that collectively regulate cell proliferation. However, roles of AR in breast cancer development and progression have not been very clearly understood. The proliferation marker Ki-67 has been confirmed as an independent predictive and prognostic factor in early breast cancer. The aims of this study are to identify the clinicopathologic associations and prognostic value of claudin 4 expression in TNBC and to correlate claudin 4 expression with AR status and Ki-67 expression. Paraffin blocks obtained from 56 female patients with triple-negative primary invasive ductal breast carcinomas were analyzed for claudin 4, AR, and Ki-67 immunohistochemical expression. High levels of claudin 4 expression were detected in 66.1% of TNBC cases. There was a significant positive correlation with age, tumor size, grade, nodal status, metastasis, and Ki-67 expression (all P < .05) and negative correlation with AR status (P < .001). Androgen receptor showed positivity in 29 cases (51.78%). There was a statistical negative correlation with the all the studied clinicopathologic parameters, claudin 4 and Ki-67 expression. High claudin 4 expression, negative AR expression, and high Ki-67 index would provide a strong prognostic power to differentiate the patients with worse outcome among TNBC patients. Moreover, target treatment for TNBC cells expressing claudin 4 or AR enriched would be valuable for future therapies.
authors.affiliation: Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt. Electronic address: monaabdelhaq@yahoo.com.
authors.forename: Mona A
authors.initials: MA
authors.lastname: Abd-Elazeem
authors.affiliation: Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: Marwa A
authors.initials: MA
authors.lastname: Abd-Elazeem
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000473:pathology; D062506:Claudin-4 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008875:Middle Aged; D011379:Prognosis; D011944:Receptors, Androgen / Q000096:biosynthesis*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C410798:AR protein, human; D014408:Biomarkers, Tumor; C568157:CLDN4 protein, human; D062506:Claudin-4; D019394:Ki-67 Antigen; D011944:Receptors, Androgen
keywords: Androgen receptors; Claudin 4; Ki-67; Triple-negative breast cancer