Antigenic characterization of medullary carcinoma of the breast: HLA-DR expression in lymph node positive cases

Medullary carcinoma of the breast has attracted attention because of its re latively good prognosis, in spite of its high cytologic grade. It has, by d efinition, a consistent, florid tumor infiltrating lymphocyte (TIL) populat ion, probably the result of cytotoxic T-lymphocytes recognizing tumor cells in an HLA-DR-restricted manner. HLA-DR tends to be more highly expressed o n primary medullary carcinoma cells than on ductal carcinoma cells; however , the MHC-class II antigenicity of the tumor cells themselves has not been analyzed extensively, and as yet there has been no comparative study of HLA -DR expression in medullary and ductal carcinomas metastatic to lymph nodes . Eleven cases of medullary carcinoma and 15 cases of ductal carcinoma, pri maries, and respective lymph node metastases were analyzed by immunoperoxid ase staining for HLA-DR and lymphocytes antigens. Polymerase chain reaction (PCR) analysis to identify HLA-DR subtypes from the paraffin blocks was pe rformed on selected cases of primaries and nodal metastases of both tumor t ypes. Immunoperoxidase staining for HLA-DR antigen revealed a marked differ ence in antigen expression between medullary and ductal carcinomas. In the medullary carcinomas, the mean percentage of cells staining for HLA-DR was 74.5% in the primary tumors and 67.3% in the nodal metastases. For the duct al carcinomas. the mean percentage of cells staining was 17.7% in the prima ries and 7% in the metastases. There was a tendency for the level of HLA-DR expression to remain high in medullary carcinoma metastatic to nodes, wher eas whatever HLA-DR was present within ductal primaries tended to diminish when cells metastasized to regional nodes. PCR analysis of the HLA-DR withi n the two tumor types revealed no emerging subtype or variant that could be associated with either the medullary or the ductal carcinomas. Medullary c arcinoma cells express much greater quantities of HLA-DR, on the whole, tha n ductal carcinomas. Expression of HLA-DR is retained on medullary carcinom a cells that have spread to lymph nodes, whereas the smaller quantities of HLA-DR present within ductal primaries tend to diminish even further when t he tumor cells are found in lymph nodes. No discernible HLA-DR mutations or predominant subtypes emerged on PCR analysis, and the authors therefore co nclude that it is the quantity and not the quality of HLA-DR expression in medullary carcinoma that maintains the characteristic TIL infiltrate, not s een in ductal carcinomas.