Cancer Immunity 3:2 (2003)

Concordant down-regulation of proto-oncogene PML and major histocompatibility antigen HLA class I expression in high-grade prostate cancer

Huiming Zhang¹, Jonathan Melamed⁴, Ping Wei², Karen Cox¹, Wendy Frankel¹, Robert R. Bahnson³, Nikki Robinson¹, Ron Pyka⁵, Yang Liu¹, and Pan Zheng¹

¹Department of Pathology, Division of Cancer Immunology, The Ohio State University Medical Center, Columbus, OH 43210
²Department of Physiology, The Ohio State University Medical Center, Columbus, OH 43210
³Department of Surgery, Division of Urology, The Ohio State University Medical Center, Columbus, OH 43210
⁴Department of Pathology, New York University Medical Center, New York, NY 10016
⁵Department of Pathology, Riverside Hospital, Columbus, OH 43214

Keywords: human, prostate cancer, immunohistochemistry, PML, MHC class I

Abstract

Recognition of tumor cells by cytolytic T lymphocytes depends on cell surface MHC class I expression. As a mechanism to evade T cell recognition, many malignant cancer cells, including those of prostate cancer, down-regulate MHC class I. For the majority of human cancers, the molecular mechanism of MHC class I down regulation is unclear, although it is well established that MHC class I down-regulation is often associated with the down-regulation of multiple genes devoted to antigen presentation. Since the promyelocytic leukemia (PML) proto-oncogene controls multiple antigen-presentation genes in some murine cancer cells, we analyzed the expression of proto-oncogene PML and MHC class I in high-grade prostate cancer. We found that 30 of 37 (81%) prostate adenocarcinoma cases with a Gleason grade of 7-8 had more than 50% down-regulation of HLA class I expression. Among these, 22 cases (73.3%) had no detectable PML protein, while 4 cases (13.3%) showed partial PML down-regulation. In contrast, all 7 cases of prostate cancer with high expression of cell surface HLA class I had high levels of PML expression. Concordant down-regulation of HLA and PML was observed in different histological patterns of prostate adenocarcinoma. These results suggest that in high-grade prostate cancer, malfunction of proto-oncogene PML is a major factor in the down-regulation of cell surface HLA class I molecules, the target molecules essential for the direct recognition of cancer cells by cytolytic T lymphocytes.