820PLOSS OF CHROMOSOMES 9P AND 14Q: RE-PROFILING METASTATIC TISSUE FOR RE-TARGETING PATIENTS WITH METASTATIC RENAL CELL CARCINOMA

ABSTRACT Aim: Loss of chromosomes 9p and 14q correlates with poor prognosis in patients (pts) with clear cell renal cell carcinoma (ccRCC). Both chromosomal loci also do harbor several hot spot molecular pathways suitable for targeted therapies. We sought to investigate the presence of losses of the hot spots chromosomal loci 9p and 14q in primary ccRCC and matched metastatic cancer tissue in pts treated with angiogenic inhibitors. Methods: 7 pts with ccRCC, with available metastatic tissue were recruited. CD10 and CD13 was performed at immunophenotypical level. Molecularly, cytogenetic interphase fluorescente in situ hybridization analysis was performed on formalin-fixed and paraffin embedded primary and matched metastatic tissues by using the locus specific probes mapping the 9p and 14q loci. Cases were scored as having loss of chromosome if >40% nuclei presented single signals and gains when >15% showed three or more signals. Results: Loss of chromosome 9p was observed in 6/7 (85%) primary ccRCC and in 6/7 (85%) matched metastases; one case showed discordance between primary tumor and metastases. Loss of chromosome 14q was detected in 4/7 (57%) primary ccRCC and in 4/7 matched metastases. The concordance of the 14q chromosomal status between primary tumors and corresponding tissue metastases was not demonstrated in 3/7 cases (42%). 3/4 cases (75%) with concordance in cytogenetic status for chromosome 14q developed metastases after at least 3 years of follow-up, the remaining within 1 year. Conclusions: Heterogeneity of cytogenetic status between metastatic and primary ccRCC is observed for loss of chromosome 14q rather than chromosome 9p. Chromosome 14q cytogenetic status, harboring the HIF-1 gene, may affect the efficacy of targeted inhibitors, whereas loss of chromosome 9p, harboring the p16 gene, seems to influence the metastatic behavior per se, without cytogenetic modulation. Those pts showing an homogeneous status for chromosome 14q loss developed metastases after longer years of follow-up. Re-profiling metastatic tissue for re-targeting pts affected by metastatic renal cell carcinoma may be proposed to overcome resistance to anti-angiogenic agents. Disclosure: All authors have declared no conflicts of interest.