Abstract
HLA expression is altered in a large variety of human cancers. We performed immunohistochemical staining on tissues from normal, preinvasive, invasive and metastatic cervical cancer tissues using anti-HLA class I or class II antibody. In tissues from normal squamous epithelium, carcinoma in situ (CIS) and microinvasive carcinoma (MIC), the expressions of HLA-B, C heavy chains and class II heavy chain were significantly decreased as disease progressed. When the expression patterns were compared between primary and metastatic squamous cell carcinoma (SCC) lesions, statistically significant down-regulation of HLA class I and class II antigen in metastatic lesions was observed. The rates of HLA-B, C heavy chains and class II heavy chain expressions were all significantly down-regulated compared to the down-regulation rate of class I beta2-microglobulin (beta2m) in invasive squamous lesions, and the expressions of class II heavy chain in metastatic lesions was decreased further than that in primary lesions. Unlike SCC, the degree of HLA class I and class II loss was not evident as disease progressed in early stage of adenocarcinoma. In invasive adenocarcinoma lesions, only the expression of HLA-B, C heavy chains was decreased and no differences were seen in HLA-B, C heavy chain expression patterns between primary and metastatic lesions. These results suggest that alterations of HLA class I and II expressions seem to occur at a particular step in cervical cancer development and depend on tissue types: when the tumor becomes invasive and starts to metastasize.
Highlights
The major histocompatibility complex (MHC) comprises a family of highly polymorphic genes encoding a set of transmembrane proteins that present peptide epitopes to specific antigen receptors on T cells (Howard et al, 1999)
When Friedman test was used for analysis, the expression patterns of HLA class I and II all showed significant differences among normal, carcinoma in situ (CIS), microinvasive squamous cell carcinoma (SCC) tissues whereas there were no significant differences between each two tissues
In a few early lesions that showed a weak HLA expression, the infiltration of T- and B-lymphocytes was observed more frequently than in areas with no HLA antigen expression. These results suggest that HLA antigens participate in the local immune response to early lesions, and that HLA expression may prevent tumor invasion to its role in the early stage of SCC of the cervix
Summary
The major histocompatibility complex (MHC) comprises a family of highly polymorphic genes encoding a set of transmembrane proteins that present peptide epitopes to specific antigen receptors on T cells (Howard et al, 1999). These antigens eventually are reduced to small peptides in the endoplasmic reticulum of the cell and transported to the cell membrane together with a particular MHC allele to interact with a T-cell receptor-CD3 complex (Townsend et al, 1989). The down-regulation of all or some HLA alleles in a particular individual by various causes breaks the polymorphism and abolishes the capacity to present antigens through MHC products. Altered HLA phenotypes could arise during any of the different steps in the biosynthetic pathway leading to HLA membrane expression, i.e. transcription-regulation defects, overexpression of protooncogene products, loss of transporter molecules, mutations in or loss of β2m gene or HLA genes, and loss of HLA haplotypes secondary to loss of heterozygosity (Browning and Dunnion, 1979; Garrido et al, 1997; Koopman et al, 1998)
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