Analysis of human lymphocyte antigen class I expression in gastric cancer by reverse transcriptase-polymerase chain...

Malignant cells have been reported to escape immune surveillance by modulation of human lymphocyte antigen (HLA) class Ia molecule and/or other accessory molecules like TAP (transporter associated with antigen processing) and beta2-M expression. Most of these reports, however, are based on immunohistochemistry techniques with polymorphic- or isotype-specific antibodies. In the present study, we have instead used a locus-specific reverse transcriptase-polymerase chain reaction-based approach to detect the transcriptional expression of HLA class Ia as well as accessory molecules in gastric cancer. Our results indicate that HLA class Ia transcript is totally absent in only approximately 9% of cancer cases. Locus-specific expression of HLA-A and -B could, however, be detected in approximately 54% cases, whereas HLA-C was expressed in most of the cancer tissues. Interestingly, in some cases where HLA class Ia expression was observed, TAP1 expression could not be detected. Furthermore, we also investigated the frequency of nonclassical or HLA class Ib expression for molecules such as HLA-E and -G. HLA-G transcript was absent in gastric tissues both in cancerous and autologous normal region, whereas HLA-E was observed in a number of gastric cancers. Altogether these selective locus-specific losses of HLA class I along with impaired expression of accessory molecules may explain the complex phenomena by which gastric tumors escape both cytotoxic T-lymphocyte- as well as natural killer cell-mediated immune defense.