Expression of DNA mismatch repair proteins hMSH2 and hMLH1 and the cyclin G1 inhibitor, p21(waf1/cip1) in pediatric tumors: correlation with response to therapy.
The expression of the DNA mismatch repair proteins hMSH2 and hMLH1 and p21(waf1) the cyclin G1 inhibitor, may determine response of adult cancers to anti-cancer drugs, that include alkylating agents and platinum-based drugs. The role of DNA mismatch repair proteins (hMSH2 and hMLH1) and p21(waf1) in pediatric tumor responses to chemotherapy and irradiation is described in the present study of 23 pediatric solid cancers (4 wilms' tumors, 9 neuroblastomas, 3 hepatoblastomas, 3 lymphomas and 4 sarcomas) using immunohistochemical methods. Immunostaining was scored for intensity (0-3) and extent (0-3). Most tumors stained strongly for hMSH2 and weakly or negative for hMLH1. All the hMLH1 negative tumors (1 wilms', 1 hepatoblastoma, 1 sarcoma, 2 lymphomas and 2 neuroblastomas) achieved complete response. p21(waf1) negative and positive tumors achieved relatively similar treatment response. The results suggest that the expression of DNA mismatch repair proteins hMLH1 and hMSH2, and p21(waf1) do not influence individual cancer responses to treatment and the results may reflect the use of multiple drugs and irradiation that cause many different types of DNA damage.
Idikio
H A
HA
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta T6G 2B7, Canada. hidikio@gpu.srv.ualberta.ca
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents / Q000627:therapeutic use; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D002648:Child; D002675:Child, Preschool; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000378:metabolism*; D018197:Hepatoblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008223:Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012509:Sarcoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein