Abstract
MHC class I antigens are intimately involved in intercellular communication, and recognition by cytotoxic T cells. Thus tumour cells that fail to express them may be at a growth or metastatic advantage. A series of ten colorectal and ten breast carcinomas, and their respective lymph node metastases, were examined immunohistologically using monoclonal antibodies (mAb) against both monomorphic and A2 polymorphic determinants, and beta-2-microglobulin (beta 2m). Four colon polypoid adenomas stained positively throughout, but 6/10 primary tumours had partial or complete loss of expression of monomorphic determinants using mAb W6/32: two node and the liver metastasis showed less, four more expression. Similar results were seen for beta 2m. HLA-A2 expression was absent or reduced in 4/4 colon tumours and all their metastases. Among the breast tumours, W6/32 staining was absent or reduced in 2/10, and node deposits showed two with less reactivity than their primary. Beta 2m staining was reduced or absent in 8/10 primaries and all the node metastases; in every case in which beta 2m was detected in the primary tumour their corresponding lymph node metastasis showed a decreased expression. HLA-A2 expression was absent or reduced in 3/4 primary breast carcinomas, and all their metastases. These results show that individual human colon and breast carcinomas often have a reduced HLA class I antigen expression, which apparently confers a metastatic advantage.
Highlights
In nine cases tumour was detected in an adjacent lymph node; four polypoid adenomas and one liver metastases were sampled
In some instances the lack of HLA class I expression is due to a loss of gene activity, as shown in a recent study (Momberg & Koch, 1989) which demonstrated the absence of beta 2m protein from human colon carcinomas to be associated with loss of messenger RNA
In a previous report we have documented the loss of both monomorphic and polymorphic HLA class I determinants in human colon carcinoma (Rees et al, 1988); in several cases primary tumours that stained with monoclonal antibodies (mAb) W6/32 failed to stain with a mAb specific for the appropriate haplotype (A2 or Bw4)
Summary
Tissue typing and specimen collectionPatients admitted to the study were undergoing surgery for carcinoma of the breast or large bowel as determined on clinical grounds. The nature of the study dictates that only cases with node metastases were acceptable, which means the tumours were relatively advanced, and generally of high grade malignancy. Patients with colorectal carcinoma were HLA typed at A and B loci using a standard microlymphocytotoxicity assay; breast tumours were typed by immunostaining for HLA A2. Tissue samples were obtained from operation specimens for carcinoma of the colon, rectum, or breast. For colorectal specimens samples of tumour, polypoid adenomas and liver metastasis (if present), normal colon 5 cm and 15 cm from the tumour, and lymph node were wrapped in aluminium foil, sprayed with 'Freezit' (Sorrisol, Merseyside) until frozen, and stored at - 80°C. Samples of tumour, normal breast and lymph node were taken and stored in a similar manner. All diagnoses were confirmed by conventional paraffin sections before acceptance into the study
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