Expression Of Mismatch Repair Genes HMLH1, HMSH2and P53, Rb In Condylomata Acuminate

Background and Objective:Human mismatch repair genes are a group of highly conserved housekeeping genes, which function in the repair of DNA damage, the maintenance of the fidelity of information transfer. hMLH1and hMSH2are the two most important genes in the human mismatch repair gene family, which maintain the fidelity of DNA replication and control gene mutations. There exists a close correlation between the functional defects caused by the loss of protein expression of hMLHl and hMSH2and the occurrence of colorectal cancer, uterine cancer and cervical cancer. It still remains unclear, however, what the mutation in hMLHl/hMSH2and its mechanism of action are in condylomata acuminate(CA). This study aims to measure the expression of hMLH1, hMSH2and p53, Rb in CA, skin squamous cell carcinoma (SCC) and normal skin tissue, and to investigate their correlation with the occurrence and development of CA.Materials and Methods:Immunohistochemistry was used to measure the protein expression of hMLHl, hMSH2and p53, Rb in surgical specimens from60cases of CA and in specimens from control groups20cases of SCC and10cases of normal skin tissues. And correlations were analyzed between the abnormal protein expression of hMLHl and hMSH2with the expression of p53and Rb proteins in CA. All the data were analyzed through Spss17.0statistical software.Results:1. The protein expression of hMLH1, hMSH2:the positive expression rates of hMLH1, hMSH2in normal skin, CA and SCC groups were90%,70%,40%and100%,80%,35%respectively, of which the expression rate in CA was higher than that in the skin carcinoma group (P<0.05). The difference was not statistically significant among the three groups (P<0.05).2.There was no correlation among the expression rates of hMLH1, hMSH2and the tissue type, the age and the gender difference in CA (P>0.05).3. The protein expression of p53:The positive expression rates of p53in normal skin, CA and skin carcinomas groups were10%,65%and55%respectively, with increased positive rates in both CA and skin carcinomas groups while there was low positive expression rate in normal skin group. The difference among the three groups was statistically significant (P<0.05).4. The expression of Rb protein:The positive expression rates of Rb in normal skin, CA and skin carcinomas groups were40%,57.3%and70%respectively, which showed a gradually increasing trend. No statistically significant difference among the three groups was found (P>0.05).5The optical density analysis:There were differences in optical density between hMLH1, hMSH2and Rb in CA and skin SCC groups, which were t=4.941, P<0.05; t=4.229, P<0.05and t=2.643, P<0.05respectively. There was no statistical significance between CA and skin SCC groups in optical density (t=1.576, P>0.05).6The analysis of correlations among various indicators in CA:Both the indicators of hMLHl and hMSH2and those of hMLHl and Rb showed a positive phase (r=0.460, r=0.803, P<0.05), which demonstrated a negative correlation with p53expression (r=-0.15, P<0.05); MSH2and Rb, a positive correlation (r=0.319, P<0.05), showing a negative correlation with p53(r=-0.416, P<0.05); Rb and p53, a negative correlation (r=-0.120, P<0.05).Conclusions:1.Compared with the normal skin group, group of CA reduced expression of hMLH1and hMSH2, compared with SCC group, group of CA increased expression of hMLH1and hMSH2, prompted the two proteins may be associate with CA, development of a certain relevance.2. hMLH1and hMSH2began to lose and mutate in CA group,suggesting that hMMR gene has been mutation or dysfunction had existed during the stage of CA.While the mutation rate of skin SCC increased, may be is due to skin squamous cell carcinoma of hMLH1, hMSH2itself mutation encoding a product of functional decline caused by the non-functional protein expression increased, thereby to increase its deletion and mutation rate.3.The positive rate of p53protein expression gradually increased in normal skin, CA and skin SCC groups, which showed that p53was correlative with the occurrence of genital condylomata and cancers.4. The expressions of Rb protein in normal skin, CA and skin carcinomas groups showed an increasing trend, but no statistically significant difference was found, suggesting that Rb pathway may not be the main cause for the occurrence of CA.5. hMLH1and hMSH2are closely related to p53, which may increase to repair damaged DNA genes in tissues of CA.