NEW ORLEANS, LA USA (UroToday.com) - In this study out of Fox Chase Cancer Center, the authors compared copy number alterations in sarcomatoid renal cell carcinoma (RCC) to those in clear cell, papillary, and chromophobe RCC in order to identify unique changes which might harbor genetic drivers of sarcomatoid RCC. Sarcomatoid differentiation develops in approximately 5% of RCC and may arise from any histologic subtype. It is associated with dismal overall survival as patients typically present with metastatic disease, and effective systemic therapy has yet to be identified.
The authors examined SNP microarrays performed on macrodissected tissue from 81 tumors, 17 of which had sarcomatoid differentiation. Copy number alterations present in over 25% of the cases were deemed significant, and significant copy number alterations in sarcomatoid specimens were compared to those found in the other 3 histologic subtypes. Sarcomatoid tumors were found to have significantly higher numbers of copy number alterations when compared to the other 3 histologies. Copy number alterations that were unique to sarcomatoid tumors included losses of 9q, 15q, 18p and q, and 22q as well as gains of 1q and 8q.
Of the cohort of sarcomatoid tumors, the authors reported that 9 arose in a background of clear cell RCC, 2 in papillary RCC, 2 in mixed clear cell and papillary RCC and 4 in unclassified RCC. Sarcomatoid patients, as expected, presented significantly more often with lymph node or distant metastatic disease. Patients with sarcomatoid tumors experienced a significantly worse overall survival. The authors reported that patients with higher numbers of copy number alterations also experience significantly worse overall survival.
The authors concluded that sarcomatoid differentiation is associated with a high rate of chromosomal imbalances. Further examination of candidate genes of interest on chromosome arms uniquely altered in sarcomatoid tumors may provide more insight into drivers of this aggressive phenotype, and ultimately may lead to the identification of novel therapeutic targets.
Presented by Timothy Ito, MD at the American Urological Association (AUA) Annual Meeting - May 15 - 19, 2015 - New Orleans, LA USA
Fox Chase Cancer Center, Philadelphia, PA USA
Reported by Philip Abbosh, MD, PhD, medical writer for UroToday.com