| Objective:To investigate the expression of succinate dehydrogenase(SDH)subunit A(SDHA)and subunit B(SDHB)in patients with renal cell carcinoma(RCC),and its relationship with clinicopathologic characteristics.Methods: The expression of SDHA and SDHB was detected in 179 cases of RCC by immunohistochemical SP two-step technique and the relationship between the SDHA and SDHB expression and clinicopathologic characteristics of RCC was analyzed.The three-dimensional structure of the SDHB wild type and mutant protein was constructed,and the mutated protein conformation was analyzed.Results:In179 cases of RCC,109 cases were male and 70 cases were female.The age ranged 24~84 years old with the median age of 57 years old.94 cases(52.5%)of tumor was located in left kidney and 85cases(47.5%)in right.The clear cell RCC in 162 cases(90.5%),papillary RCC in 9 cases(5.0%),chromophobe cell RCC in 5 cases(2.8%)and multilocular cystic RCC in 3(1.7%).The well-differentiated group had 156 cases(87.1%),moderatelydifferentiated group had 20 cases(11.2%)and poorly-differentiatied group had 3 cases(1.7%).165 cases(92.2%)positively expressed SDHA,1 cases(0.6%)negatively expressed it and 13 cases(7.3%)suspicious-negative expressed it.173 cases(96.6%)positively expressed SDHB,3 cases(1.7%)negatively expressed it and 3 cases(1.7%)suspiciously-negative expressed it.The difference in the expression of SDHA between the different pathological grade was statistically significant(P<0.05)and in the expression of SDHB between the different pathological grade were no statistically significant(P>0.05).It had no statistically significant difference among different gender,age,location and histological types(P>0.05).There were 18 cases(10.1%)of SDHA and SDHB expressed negatively or suspiciously-negative.2 cases(1.12%)was SDHA and SDHB expressed both suspicious negative.In 18 cases of SDH-deficient RCC,9 cases(5.03%)was male and 9 cases(5.03%)was female,The age ranged 39~78 years old with the median age of 55.5 years old.12 cases(66.7%)of tumor was located in left kidney and 6 cases(33.3%)in right kidney.The clear cell RCC in 17 cases(94.5%)and papillary RCC in 1 cases(5.5%).In 17 cases SDH-deficient RCC,1 cases(5.9%)was accompanied with cystic degeneration and 1 cases(5.9%)was accompanied with sarcomatous change.The well-differentiated group had 15 cases(83.3%),moderately-differentiatied group had 1 cases(5.6%)and poorly-differentiatied group had 2 cases(11.1%).Well-differentiated group was more common.Most of SDH negative and suspicious negative RCC had the following characteristics: The tumor was composed of polygonal cells arranged in nest that was separated by fine fibrovascular stroma.The nuclei were round with vesicular chromatin.Normal renal tubule could be seen within the tumor,the cytoplasm of tumor cells was eosinophilic flocculet material,vacuole and eosinophilic inclusion body.PCR amplification was successful.In 18 cases SDHA/SDHB protein expression negatively/suspicious-negatively,1 case showed SDHB gene exon 3 point mutations,1 case showed SDHB gene exon 4 point mutations,1 case showed SDHB gene exon 6 point mutations,SDHA gene mutation was not found.Mutants may cause hydrophilic properties,stability and functional changes.18 cases SDHA/SDHB protein expression negatively/suspicious-negatively RCC in 2 cases of were followed,including 1 case with no tumor recurrence,1 case died after 6 months(for unknown reasons).Conclusion: The vast majority of RCC cases express SDHA and SDHB protein(positive)while a few cases loss of these protein expression(negative).The RCC cases which lack of SDHA and SDHB protein expression have unique histological features and the significantly higher incidence of left kidney than right kidney.SDHA/SDHB protein expression negatively/suspicious-negatively RCC should be further detected SDHA and SDHB gene mutation. |
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