Abstract
Expression of HLA antigens and beta 2-microglobulin was studied by immunoperoxidase staining of frozen sections of 9 mucinous and 10 nonmucinous colorectal adenocarcinomas, 1 cloacogenic carcinoma, 12 colorectal adenomas and 4 samples of normal colorectal mucosa using monoclonal antibodies (MAbs). Staining results were related to histopathological features. HLA Class I antigens were strongly expressed in morphologically normal colorectal epithelium, in all adenomas tested and in all non-mucinous carcinomas. In contrast, expression of HLA class I antigens by the majority of tumour cells was present in only 2 of the 9 mucinous carcinomas, whereas 2 of these mucinous carcinomas were completely negative. In the mucinous carcinomas a striking scarcity of mononuclear inflammatory infiltrate, especially around the mucus accumulations, was observed. HLA class II antigen expression was not detected in normal epithelium and was only focally present in 1 of the 12 adenomas. In 6 out of the 20 carcinomas tested between 20% and 90% of the tumour cells were stained by MAbs against HLA class II antigens. Apart from the low expression of HLA class I antigens in mucinous carcinomas no relationship was found between expression of HLA antigens and histological features of the tumours. The relative poor prognosis of mucinous colorectal carcinoma as reported in the literature may be associated with low expression of HLA class I antigens and scant mononuclear inflammatory infiltrate, which may be a reflection of a weak immune response to the tumour cells.
Highlights
In view of the role played by HLA class II antigens in cell-cell interactions required to generate immune responses (Thorsby et al, 1976) and by HLA class I antigens in the interaction between target cells and cytotoxic T-cells (McMichael, 1980) we investigated a series of mucinous and non-mucinous colorectal carcinomas for expression of HLA antigens in relation to the degree of mononuclear infiltrate
The present study shows that HLA class I antigens and f2 microglobulin are expressed by morphologically normal colorectal epithelium, by all colorectal adenomas examined and only by varying proportions of tumour cells in colorectal adenocarcinomas
In preliminary Northern blotting experiments using a DNA probe specific for HLA class I mRNA of 5 carcinomas of which enough frozen tissue was available (Figure 3) we found that in one of the two mucinous carcinomas with low or absent HLA class I expression a low level of mRNA coding for HLA class I antigens was present
Summary
The material consisted of 12 adenomas and 20 carcinomas The MAb Q5/13 histologically normal anal mucosa were brightly stained by recognizing a monomorphic determinant of HLA class II the anti HLA class I MAbs CR1, W6/32 and BRL and the antigens was developed and characterized as described else- anti f2m MAb OLAC. HLA-DR antibody, was purchased from Bethesda Research The majority of tumour cells in all the adenomas and in Laboratories, Inc. Control mouse ascites was purchased most of the adenocarcinomas tested showed marked staining from Bethesda Research Laboratories Inc. with the anti HLA class I and anti fl2m MAbs (Tables I and II; Figure 1). In normal mucosa adjacent to carcinomas the percentage of epithelial cells stained by the anti class I MHC (Dako Immunoglobulins, Copenhagen, Denmark). Note the marked staining of the stromal septa (cryostat section, x 400, haematoxylin counterstain)
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