Analysis of MHC class I and II expression in relation to presence of HPV genotypes in premalignant and malignant cervical lesions

Abstract

Summary Cervical intraepithelial neoplasia (CIN) grades I to III lesions (n = 94) and squamous cell carcinomas of the uterine cervix (n = 27) were analysed for MHC class I and II expression and presence of HPV genotypes.MHC class I and II expression was studied by immunohistochemistry and HPV typing was performed by general primer-and type-specific primer mediated PCR (GP/TS PCR). Both A central role in the antigen-specific immune response is played by the major histocompatibility complex (MHC), which are cell surface proteins that act as restricting elements in the recognition of antigen by T-cells. MHC class I (MHC-I) present endogenous antigen to cytotoxic T-lymphocytes (CTLs). Low levels or lack of MHC-I surface expression can consequently render aberrant cells non-immunogenic to CTLs, and may provide a way for cells to escape immune surveillance. MHC-1 alterations have been described in human cancer of different sites of the body (see review RuizCabello et al., 1991).Generally, MHC class II (MHC-II) surface expression is restricted to specialised antigen presenting cells (APCs), that present mainly opsonised exogenous antigen to T-helper cells. Recognition leads to activated T-cells, which can stimulate B-cell, CTL proliferation and MHC non-restricted killing by natural killer (NK) cells or activated macrophages. Occasionally, other cells like neoplastic epithelial cells have been described to express MHC-II, which could assist in the onset of the cellular immune response (Ostrand-Rosenberg et al., 1991).Infections with specific human papillomavirus (HPV) types are strongly associated with the development of cervical cancer, with HPV types 16 and 18 as the most predominant types (Zur Hausen, 1989 (Connor & Stern, 1990;Glew et al., 1992), suggesting that changes in the presentation of viral tumour antigens to the cellular immune system can occur. However, to get insight whether altered MHC-I and -II expression is related to the development of cervical cancer from its premalignant lesions, it is necessary to study dysplastic cervical lesions (CIN) for the MHC-I and -II status.Tumour virus based mechanisms have been described that specifically influence MHC-I cell surface expression (Signas et al., 1982;Schrier et al., 1983). Similar mechanisms could exist for HPV affecting antigen presentation of the infected cells. However, little is known about MHC alterations in CIN lesions in relation to the presence of different HPV genotypes.Therefore in this study expression of MHC-I and -II was investigated in CIN lesions of different grades and cervical carcinomas. HPV typing was carried out by a combined general primer-mediated (GP-) and type-specific (TS-) polymerase chain reaction (PCR) strategy (van den Brule et al., 1991;Walboomers et al., 1992). In addition, HPV RNA in situ hybridisation (RISH) was applied to some HPV 16 PCR positive lesions, in order to localise cells containing transcriptionally active HPV 16 in relation to altered MHC expression. The results indicate that MHC-I and -II alterations are also...

Assessment of cytotoxic T-lymphocyte phenotype using the specific markers granzyme B and TIA-1 in cervical neoplastic lesions

“…Secondly, MHC class I alleles are down-regulated on the surface of neoplastic cells, as has been previously shown in several studies for both premalignant and malignant lesions (Connor and Stern, 1990;Cromme et al, 1993). This lower expression or even complete absence of MHC class I molecules on tumour cells could affect their recognition and lysis by CTLs (Rivoltini et al, 1995).…”

“…An active role for the cellular immune system in the prevention of the development of cervical cancer is evidenced by a higher incidence of HPV-associated premalignant lesions in immunocompromised patients, such as AIDS patients and transplant recipients (Halpert et al, 1986;Laga et al, 1992). However, we and others have shown that major histocompatibility complex (MHC) class I expression is frequently down-regulated on neoplastic cells in malignant and premalignant lesions (Connor and Stem, 1990;Cromme et al, 1993;Honma et al, 1994;Keating et al, 1995). Lower expression or even complete absence of MHC class I molecules on tumour cells could affect their lysis by cytotoxic T cells as has been shown in melanomas (Rivoltini et al, 1995).…”

Alterations of HLA class I and II antigen expression in preinvasive, invasive and metastatic cervical cancers

“…Decreased HLA expression was not correlated with the presence of human papillomavirus 16 or 18 in cervical cancers (Cromme et al, 1993a). It has been suggested that down-regulation of class I MHC expression in cervical cancers is apparently post-transcriptionally controlled (Cromme et al, 1993b).…”

Overexpression of p16INK4A as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri

“…56 Briefly, five consecutive sections (4 m) were suspended in 150 l of digestion buffer containing 1% SDS, 0.5 M Tris-HCl, 20 mM EDTA, 10 mM NaCl and proteinase K (2 l of 20 mg/ml stock solution). Samples were incubated with shaking at 56°C for 12 to 24 hr followed by inactivation of proteinase K at 96°C for 10 min.…”