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Indian Journal of Pathology and Oncology


Invasive breast carcinoma: Correlation with the molecular subtypes and pathological response to neo-adjuvant chemotherapy


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Author Details: Shanmuga Priya S., Rajalakshmi V., Veena Bheeman

Volume : 4

Issue : 2

Online ISSN : 2394-6792

Print ISSN : 2394-6784

Article First Page : 318

Article End Page : 323


Abstract

Introduction: Breast cancer is the most commonly occurring cancer in females and leading cause of cancer related deaths worldwide. The analysis of gene expression data have suggested that breast carcinoma can be divided into molecular subtypes which have distinct clinical features, different prognosis and clinical outcome. Claudins are members of a large family of tight junction proteins that regulate cell adhesion. Currently there are 40 claudins that are variably expressed in several cancers. Only few studies have examined their expression in breast carcinomas. Recently subtype of claudin with low expression has been described that has a prognostic and predictive indication in relation to response following neoadjuvant chemotherapy.
Aim: The aim of this study was to classify breast tumors into the molecular patterns based on the expression of estrogen receptor, progesterone receptor and her-2 neu and to evaluate the expression of claudin, ki-67 and p-53 in invasive breast carcinoma. Pathological response following neoadjuvant chemotherapy was assessed in different molecular patterns of invasive breast carcinomas correlating with expression of claudins.
Materials and Method: A retrospective analysis of 100 breast carcinomas immunostained with ER, PR and her-2-neu were performed and tumors were subtyped into molecular patterns. Immunostaining with ki-67 and p-53 was done in 43 cases to assess the pathological response to neoadjuvant chemotherapy. Claudin 1, 3, 4, and 7 was tested in 43 cases by RT-
PCR method.
Results: Of 100 cases of invasive breast carcinomas diagnosed and immunostained during the 5-year period from 2012-2016, basal-cell type accounts to 20 cases, followed by her-2 enriched type (17 cases), luminal -A (47 cases) and luminal-B (16 cases). Claudin was expressed in luminal A (44.2%), luminal B (26%), basal (16.3%) and her-2 enriched (14%) subtype. Incidence of claudin low was seen in 14% of T2-4 lesions, 7% nodal metastasis and 9.3% of high grade tumors. Pathological response was better for basal-like type when compared to other subtypes.Ki-67 expression was high among triple negative tumors when compared to non-triple negative tumors. Pathological response was good in basal-like subtype when p-53 was expressed.
Conclusion: The histopathological examination of the tumor helps in assessing the response following neoadjuvant chemotherapy and can be correlated with expression of claudin, ki-67 and p-53.Claudin-low subtype can be seen in triple negative, luminal A& B and her-2 enriched type. More number of cases need to be studied in future to assess the response rate in claudin –low tumors as this has direct impact on current therapeutic strategies and follow-up is mandatory to look for recurrences.

Key words:
Breast Carcinoma, Molecular Patterns, Claudin, ki-67, Pathological Response