Co-mutation of p53,K-rasgenes and accumulation of p53 protein and its correlation to clinicopatholog

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AIM:To determine the accuracy of p53 gene mutations predictedby overexpression of p53 protein immunohistochemically,and to investigate the co-mutation of p53 and K-rasgenesin rectal cancer and its effect on promoting malignant biologicbehaviors of tumors.METHODS:Ninety-seven specimens of rectal cancer weresurgically resected in our hospital from August 1996 toOctober 1997.The hot mutation areas of p53 gene (inexons 5-8) and K-rasgene (in codon 5/12 and 13) weredetected with polymerase chain reaction-single strand con-formation polymorphism (PCR-SSCP),and overexpressionof p53 protein was detected with immunohistochemistry(IHC) in the 97 specimens of rectal cancer.Correlationbetween gene mutations and tumor clinicopathologic factorswas studied,and survival analysis was penfomed as well.RESULTS:There were 36 cases of p53 gene mutations in61 p53 protein positive cases,and 21 cases of p53 genenon-mutation in 36 p53 protein negative cases respectively.The coincidence rate of p53 gene mutation by IHC methodwith PCR-SSCP method was 58.8% (57/97).The mutationrate of p53 gene was 52.6% (51/97),while K-ras genemutation was observed in codons 12 and 13 in 61 caseswith a mutation rate of 62.9% (61/97).Single gene mutationof p53 or K-raswas found in 32 cases.Both p53 and K-rasgene mutation were found in 48 cases.Statistical analysisshowed that p53 and K-ras gene mutations were not relatedto the clinicopathologic factors,including tumor size,grosstumor type,histological classification,differentiation,invasionto intestinal veins,lymphatics and nerves,invasive depth towall,lymph node metastasis,and Dukes’ stages (P>0.05).The survival in patients with no gene mutation,single genemutation and both gene mutations were similar (P>0.05).CONCLUSION:IHC has a certain false positive and falsenegative rate in detecting p53 gene mutations.Malignantbiological behaviours of rectal cancer are not enhanced byp53 and K-rasgene mutations.Co-mutation of p53 and K-rasgene has neither synergic carcinogenesis-promoting effect,nor prognostic effect on rectal cancer. AIM: To determine the accuracy of p53 gene mutations predicted overexpression of p53 protein immunohistochemically, and to investigate the co-mutation of p53 and K-rasgenes in rectal cancer and its effect on promoting malignant biologic behaviors of tumors. METHODS: Ninety-seven specimens of rectal cancer weresurgically resected in our hospital from August 1996 to October 1997. The hot mutation areas of p53 gene (inexons 5-8) and K-rasgene (in codon 5/12 and 13) weredetected with polymerase chain reaction-single strand con-formation polymorphism (PCR-SSCP), and overexpression of p53 protein was detected with immunohistochemistry (IHC) in the 97 specimens of rectal cancer. Correlation between gene mutations and tumor clinicopathologic factorswas studied, and survival analysis was penfomed as well .RESULTS: There were 36 cases of p53 gene mutations in 61 p53 protein positive cases, and 21 cases of p53 gene non-mutation in 36 p53 protein negative cases respectively. coincidence rate of p53 gene mutatio n by IHC method with PCR-SSCP method was 58.8% (57/97). The mutation rate of p53 gene was 52.6% (51/97), while K-ras genemutation was observed in codons 12 and 13 in 61 cases with a mutation rate of 62.9% (61/97). Single gene mutationof p53 or K-raswas found in 32 cases.Both p53 and K-rasgene mutations were found in 48 cases. Statistical analysis of p53 and K-ras gene mutations were not related to the clinicopathologic factors , including tumor size, grosstumor type, histological classification, differentiation, invasion to intestinal veins, lymphatics and nerves, invasive depth towalls, lymph node metastasis, and Dukes’ stages (P> 0.05) .the survival in patients with no gene mutation, single genemutation CONCLUSION: IHC has a certain false positive and falsenegative rate of detecting p53 gene mutations. Malignant biological behavieties of rectal cancer are not enhanced by p53 and K-rasgene mutations. Co-mutation of p53 and K-rasgene has neither synergic carcinogenesis-promoting effect, nor prognostic effect on rectal cancer.
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