Overexpression of Calreticulin in Malignant and Benign Breast Tumors: Relationship with Humoral Immunity

Abstract

Objective: Calreticulin is a multicompartmental protein which regulates many important cellular responses. The aim of this study was to elucidate whether the intensity and location of calreticulin overexpression in tumor cells are related to the elevated humoral immunity to calreticulin in patients with benign or malignant breast disease. Methods: This study involved 27 patients with benign and 58 patients with malignant breast tumors before surgical resection and 38 healthy volunteers. Cytoplasmatic or membranous calreticulin overexpression in malignant or benign cells in paraffin-embedded tissues was determined using immunohistochemistry. Levels of the serum anti-calreticulin autoantibodies were detected by ELISA. Results: Statistically significant differences between serum levels of IgA of anti-calreticulin antibodies in controls and patients with breast tumors, and between controls and patients with nonmalignant breast diseases were found, but no statistically significant differences were found between levels of serum IgG anti-calreticulin antibodies. Humoral immunity to calreticulin developed against cytoplasmatic and co-localized membranous calreticulin was not correlated to the intensity of its overexpression and was present even in the absence of its membranous localization. Conclusions: The degree of calreticulin overexpression in lobular breast carcinoma is lower than in ductal breast carcinoma. Elevated concentrations of anti-calreticulin IgA antibodies were present more frequently in patients with metastasis in locoregional lymph nodes in comparison to anti-calreticulin IgG antibodies.