Clinical Utility of Fluorescence In Situ Hybridization (FISH) for Deletion of Chromosome 3p in the Work-up of Renal Masses

Chromosome 3p deletion is a well-established genetic aberration in clear cell renal cell carcinoma (RCC). We aimed to evaluate the clinical utility of 3p fluorescence in situ hybridization (FISH) on formalin-fixed paraffin-embedded tissue in surgical pathology specimens. 3p:3q <0.8 was established as the cut-off for 3p loss. The 2015 Medicare allowable billing rates were used to estimate the cost. Over 2.5 years (2013 to 2015), 3p FISH was performed on 18 cases per year. Among tested cases, 70% (30/43) were nephrectomies and 30% (14/43) metastases. 3p loss was detected in 44% (19/43) of cases, with a higher rate of loss in radical compared with partial nephrectomies (71% vs. 15%; P=0.003). A definitive RCC subtype was assigned in 65% (28/43) of cases. More partial nephrectomies had a definitive subtype assigned, compared with radical nephrectomies (92% vs. 59%; P=0.04), possibly related to more high-grade, high-stage tumors in submitted radical nephrectomies. Tested nephrectomies were most commonly diagnosed as clear cell (41%) or clear cell papillary RCC (32%). Half of unclassifiable RCCs had 3p loss (53%, 8/15). Annual 3p FISH costs were $3446.64, with 79% of costs from ancillary studies attributable to immunostains. 3p FISH was performed infrequently in nephrectomy specimens and was not cost prohibitive. RCC cases that are unclassifiable by morphology and other ancillary tests, but which have 3p FISH deletion may merit a comment in the pathology report, raising the possibility of clear cell RCC, as the oncologic approach may be altered despite the lack of a definitive RCC subtype.