ABSTRACT
We investigated the immunohistochemical expression of p21/waf1 protein in 59 cases of nasopharyngeal carcinomas (NPC) and compared p21 expression with PCNA, p53 and mdm2 protein expression. We found p21, PCNA, p53 and mdm2 in 59/59, 59/59, 18/59 and 12/59 nasopharyngeal carcinomas, respectively. We observed a tendency to a relationship between high expression of PCNA (> 25% positivity in tumour cells) and low expression of p21 protein. Parallel p53/p21 protein expression was found in 18 cases. Twelve were also mdm2 positive. This pattern may represent NPC with wild type (wt) p53 since mdm2 and p21 proteins are inducible by wt p53 gene. In these cases p53 protein expression may be due to stabilisation to mdm2 protein. This could be important in the pathogenesis of these cases since mdm2 may deregulate the p53-dependent growth suppressive pathway. Discordant p53-/p21+ protein expression was found in 41 cases. All were also mdm2 negative. This pattern suggests immunohistochemically undetectable wt p53 gene which is able to induce p21 protein expression.
Subject(s)
Carcinoma/metabolism , Cyclins/metabolism , Nasopharyngeal Neoplasms/metabolism , Nuclear Proteins , Cyclin-Dependent Kinase Inhibitor p21 , Humans , Immunohistochemistry , Neoplasm Proteins/metabolism , Proliferating Cell Nuclear Antigen/metabolism , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-mdm2 , Tumor Suppressor Protein p53/metabolismABSTRACT
The MIB1 monoclonal antibody which is used as a marker of cell proliferation was studied by immunohistochemistry on formalin-fixed and paraffin embedded biopsy specimens of lymph nodes in 40 high- and 46 lowgrade cases of non-Hodgkin's lymphomas (NHL) classified according to the Kiel classification. All cases were found to display nuclear MIB1 staining. A statistically significant difference (P < 0.005) was found between high- and low grade NHLs and this indicates that the high- grade NHL display a higher proliferation rate than low grade. In addition, remarkable variations in MIB1 expression were found among individual cases of the same histological group. These data may suggest that MIB1 index can help in the individual approach of the proliferation rate of each tumour and this may be an important parameter in association with clinical and other laboratory parameters for predicting the biological behaviour of non-Hodgkin's lymphomas.
Subject(s)
Ki-67 Antigen/analysis , Lymphoma, Non-Hodgkin/pathology , Antibodies, Monoclonal/immunology , Cell Division , Humans , ImmunohistochemistryABSTRACT
We have investigated the immunohistochemical expression of beta2-microglobulin and HLA-DR proteins in Hodgkin's disease (HD) in relation to the expression of the EBV-encoded EBER1-2 mRNAs and the LMP-1 protein. beta2-microglobulin is expressed in association with MHC-I molecules on most nucleated cells and HLA-DR belongs to the MHC-II molecules which are expressed mostly on antigen-presenting cells. Formalin-fixed paraffin embedded tissue from 39 cases of lymphonodal HD were stained by immunohistochemistry for beta2-microglobulin, HLA-DR and LMP-1 proteins and by RNA in situ hybridization for EBER1-2 mRNAs. beta2-microglobulin positive staining was found in Reed-Sternberg and Hodgkin cells (HRS cells) in 18/39 cases of HD. HLA-DR positive staining was found in HRS cells in all cases of HD. EBER1-2 transcripts and LMP-1 protein were detected in HRS cells in 16/39 cases of HD. No correlation as found between the presence of EBER 1-2 transcripts or the LMP-1 protein and the detection of beta2-microglobulin and HLA-DR proteins in HD. Thus, EBV does not seem to use downregulation of MHC-I to avoid the T-cell cytotoxic immune response in HD. In addition, EBV does not seem to be the only factor responsible for the HLA-DR expression in HRS cells of HD, although it could participate in the induction of the expression of HLA-DR molecule in the EBV positive cases of HD.
Subject(s)
Herpesvirus 4, Human , Histocompatibility Antigens Class II/analysis , Histocompatibility Antigens Class I/analysis , Hodgkin Disease/immunology , Hodgkin Disease/virology , Tumor Virus Infections/immunology , beta 2-Microglobulin/analysis , Humans , In Situ Hybridization , RNA, Messenger/analysis , RNA, Viral/analysisABSTRACT
We have investigated the immunohistochemical expression of beta 2-microglobulin and HLA-DR proteins in nasopharyngeal carcinoma (NPC) in relation to the expression of the Epstein-Barr virus (EBV)-encoded EBER 1-2 mRNAs and LMP-1 protein. beta 2-Microglobulin is expressed in association with MHC-I molecules on most nucleated cells and HLA-DR belongs to the MHC-II molecules which are expressed mostly on antigen-presenting cells. Formalin-fixed paraffin-embedded tissue from 37 NPC cases was stained with immunohistochemistry for beta 2-microglobulin, HLA-DR and LMP-1 proteins and by RNA in situ hybridization for EBER 1-2 mRNAs. beta 2-Microglobulin-positive staining was found in neoplastic cells in all cases. In 19/37 NPC cases the positive staining was found in most neoplastic cells. In the remaining 18 NPC cases more than 25% of the neoplastic cells showed significantly reduced or negative staining in comparison to the normal epithelium and infiltrating small lymphocytes. HLA-DR-positive staining was found in 27/37 NPC cases. EBER 1-2 transcripts were deteced in neoplastic cells in 13/37 NPC cases. LMP-1 expression in tumour cells was found in 4/13 EBER1-2-positive cases. No correlation was found between the presence of EBER1-2 transcripts or LMP-1 protein and the beta 2-microglobulin-reduced expression in NPC. Thus, EBV does not seem to use downregulation of MHC-I to avoid the T cell cytotoxic immune response in NPC. HLA-DR expression was observed in all 13 EBV-positive cases of NPC, suggesting that EBV may participate in the induction of HLA-DR expression in a proportion of NPC.
