Correlation of tumor-infiltrative lymphocyte subtypes alteration with neoangiogenesis before and after neoadjuvant chemotherapy treatment in breast cancer patients

• Published in: The International journal of biological markers 2014-09, Vol.29 (3), p.e193-e203
• Main Authors: Chan, Monica S M, Chen, Shi-Fan, Felizola, Saulo J A, Wang, Lin, Nemoto, Noriko, Tamaki, Kentaro, Ishida, Takanori, Chow, Louis W C, Ohuchi, Noriaki, Sasano, Hironobu
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - immunology; Breast Neoplasms - blood supply; Breast Neoplasms - drug therapy; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - blood supply; Carcinoma, Ductal, Breast - drug therapy; Carcinoma, Ductal, Breast - immunology; Carcinoma, Ductal, Breast - pathology; Cyclophosphamide - administration & dosage; Epirubicin - administration & dosage; Female; Fluorouracil - administration & dosage; Forkhead Transcription Factors - immunology; Humans; Immunohistochemistry; Immunophenotyping; Lymphocyte Subsets - drug effects; Lymphocyte Subsets - immunology; Lymphocytes, Tumor-Infiltrating - immunology; Neoadjuvant Therapy; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - immunology; Platelet Endothelial Cell Adhesion Molecule-1 - immunology; Stromal Cells - pathology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Regulatory - immunology; Taxoids - administration & dosage; Tumor Microenvironment
• ISSN: 1724-6008
• DOI: 10.5301/jbm.5000082

The two most important factors in tumor-stromal interactions are tumor-infiltrating lymphocytes (TIL) and neoangiogenesis (NAng). While changes of these parameters in responders of neoadjuvant chemotherapy (NCTx) have been reported, their correlation with pathological response in breast cancer (BC) patients treated with NCTx have not been described. We therefore evaluated alterations of the TIL subtypes ratio and alterations of NAng using the vasohibin-1-positive ratio (VPR) in BC patients during the course of NCTx. To this aim we used: (i) double immunohistochemistry of CD8 cytotoxic T cells and T regulatory cells (Treg) with Foxp3, determining the CD8+/Foxp3 ratio; (ii) immunostaining of CD31 and vasohibin-1, yielding the VPR, which reflects the NAng status. Changes between the CD8+/Foxp3 ratio and VPR before and after therapy were then correlated with the pathological response of the patients. A concomitant significant decrement of Foxp3 and NAng, represented by VPR, were detected only in NCTx pathological responders (p