Combining interphase and metaphase analyses in the differential diagnosis among renal cell neoplasms with distal nephron differentiation

Cytogenetic analysis usually reveals low number of chromosomes 1, 2, 6, 10 and 17 in chromophobe renal cell carcinoma and a normal numerical complement of chromosomes in renal oncocytoma. However, different chromosomal patterns have been rarely reported in both renal cell neoplasms. We investigated 23 renal cell neoplasms (11 chromophobe renal cell carcinomas, 12 renal oncocytomas) by metaphase karyotyping and interphase FISH for chromosomes 1, 2, 6, 10 and 17 and flow cytometric analyses on tissue sections. FISH showed losses of two or more chromosomes in 10 chromophobe renal cell carcinomas (91%) and gains of multiple chromosomes in one (9%). Six (50%) renal oncocytomas were totally disomic, five (42%) showed one chromosomal loss (chromosome 1 in 3 cases), one case (8%) two losses. Among 9 chromophobe renal cell carcinomas with available istograms 6 (67%) showed aneuploid stemlines whereas the three remaining and 8/9 (89%) renal oncocytomas were diploid. Karyotypically, 3 chromophobe renal cell carcinomas (33%) were hypodiploid, 3 (33%) were polydiploid, one (11%) was diploid and 4 (36%) failed to grow. Nine out of 12 (75%) renal oncocytomas were diploid, one showed -Y (8%), one 47,XX,+7 (8%), one multiple different clones (9%). All chromophobe renal carcinomas which failed to grow and 2/3 (75%) showing gains by metaphase analyses displayed multiple chromosomal losses by FISH. Eight renal oncocytomas with normal DNA content and those three with additional chromosomal abnormalities (91%) by karyotyping showed normal complement of chromosomes by FISH. Conclusion: 1) chromophobe renal carcinomas usually display multiple chromosomal losses by FISH analysis in spite of a different spectrum found by karyotyping and flow cytometric analyses; 2) chromophobe renal carcinomas that fail to grow in culture are characterized by chromosomal losses in FISH; 3) renal oncocytomas usually show a normal numerical complement of chromosomes by both interphase and metaphase analyses.