Clonal Origin Of Multifocal Clear Cell Renal Cell Carcinoma Studied By X-chromosome Inactivation

Objective:Nephron sparing surgery (NSS) has been widely accepted as a major treatment for early localized renal cell carcinoma. Multicentricity is one of the important factors that cause postoperative local recurrence. Our previous studies had proven that clear cell renal cell carcinoma is (cc-RCC) monoclonal origin tumors. In female patients, the most accurate marker in detecting the origin of tumor clones is non-random X-chromosome inactivation. This prospective study was designed to study the clonal origin of multifocal clear cell renal cell carcinoma.Methods:44 tissue specimens were taken from radical nephrectomy samples of 11 cases of female patients with pathologically proven clear cell renal cell carcinoma and corresponding normal kidney. Genomic DNA was extracted. After Hha I digestion of the human androgen receptor (HUMARA), gene fragment was done polymerase chain reaction (PCR) and electrophoresis, and stained by silver nitrate, and electrophoretic band was observed and studied to determine the status of its clonality.Results:HUMARA gene heterozygosity rate was 90.9%(10/11). The same pattern of the X-chromosome inactivation between the primary tumor and multicentric foci was noticed in 90%(9/10) of cc-RCC patients, while different pattern of X-chromosome inactivation was also observed in one patient (10%,1/10),Conclusions:Majority of the multifocal cc-RCC has same pattern of X-chromosome inactivation, which implies a possible monoclonal origin of the primary tumor and the multifocal lesion, i.e. the satellite lesion is the most probably a result of intrarenal metastasis. While a small portion of the cases also reveal a different X-chromosome inactivation pattern, the evidence of multiclonal origin, i.e. the multiple tumors in the same kidney were independently originated. More studies are needed to confirm these conclusions.