Histocompatibility antigens in primary and metastatic squamous cell carcinoma of the larynx

Abstract

A series of 38 primary laryngeal and hypopharyngeal tumours, 15 lymph-node metastases and normal tissue were evaluated in frozen sections for the expression of MHC class I and II antigens, using monomorphic monoclonal antibodies (MAbs) to HLA-ABC, beta 2-microglobulin, DR, DP, DQ, HLA-B and polymorphic HLA-ABC antigens. Normal distant mucosa of larynx reacted to anti-class I antibodies but not to anti-class II. In 9 primary tumours (23.7%) HLA class I antigens were not observed. The remaining 29 showed a strong reaction to not observed. The remaining 29 showed a strong reaction to anti-HLA-ABC (heavy chain) and anti-beta 2-microglobulin, although in 3 cases out of 29 no staining was observed with anti-HLA-B locus-specific MAbs. These selective losses were confirmed using the corresponding anti-HLA polymorphic MAbs. For HLA class II molecules, only DR was observed in 3 of 38 cases. Defective HLA class I expression statistically correlates with high scores according to Jakobsson's criteria for histopathological tumour grading. Loss of HLA-ABC antigens was most frequent among the cases with poor differentiation (6/8 cases). On the contrary, class II antigen expression was correlated with a well differentiated pattern and a more favourable prognosis (p less than 0.001). We have found differences in HLA class I expression when comparing primary tumours and autologous metastases (3/9 cases). Immunoprecipitation and SDS-PAGE of class I antigens, Northern and Southern blot analyses of MHC class I genes were performed. We have not detected class I gene rearrangement using HLA coding and locus-specific non-coding probes. However, we have found a class I transcription defect that corresponds with a class-I-negative phenotype.

Expression of Hla-Class II Antigen in Gastric Carcinomas: Its relationship to histopathological grade, lymphocyte infiltration and five-year survival rate

“…This is in agreement with results reported by David & Kevin (10) and Sakai et al (15). In human tumors, the expression of HLA-DR antigen has been reported to be associated with histological degree of cell differentiation (8,9,16). In the present study, the differentiated-type gastric carcinomas expressed HLA-DR antigen more frequently than undifferentiated-type carcinomas.…”

“…be associated with well-differentiated states of the tumor cells, and the tumors with HLA-DR antigen expression have a good prognosis (8,9).…”

Differences in MHC and TAP-1 expression in cervical cancer lymph node metastases as compared with the primary tumours

“…Such down-regulation would supply a selective growth advantage for malignant tumours by allowing neoplastic cells to escape CTL-mediated destruction. Indeed when class I MHC expression is lost in breast (Concha et al, 1991) or laryngeal (Esteban et al, 1989) carcinomas, a significantly poorer clinical outcome is found.…”

Loss of monomorphic and polymorphic HLA antigens in metastatic breast and colon carcinoma

“…The class I MHC molecule consists of three alpha regimes, covalently linked to beta-2-microglobulin (beta 2m), which are encoded by separate genes, and linked prior to expression at the cell membrane (Ploegh et al, 1981;Arce-Gomez, 1978 (Eisenbach et al, 1983;1985). Studies on the expression of human MHC class I antigens in primary vs metastatic tumour are limited; for example malignant melanoma, digestive tract, and laryngeal tumours (Ruiz-Cabello et al, 1989;Esteban et al, 1989). In these studies, both increased and decreased expression of monomorphic determinants of HLA class I was observed in the metastases compared with their primaries.…”

“…With these immunogenic tumours, those with a high level of MHC antigen expression show low metastatic ability; transfection and subsequent expression of the H2K gene into otherwise highly metastatic H2K-negative tumour cell variants reduces tumour growth, and prevents metastasis (Eisenbach et al, 1983;1985). Studies on the expression of human MHC class I antigens in primary vs metastatic tumour are limited; for example malignant melanoma, digestive tract, and laryngeal tumours (Ruiz-Cabello et al, 1989;Esteban et al, 1989). In these studies, both increased and decreased expression of monomorphic determinants of HLA class I was observed in the metastases compared with their primaries.…”