Renal oncocytomas with 11q13 rearrangements: cytogenetic, molecular, and immunohistochemical analysis of cyclin D1

Two groups of renal oncocytomas have been cytogenetically defined by the loss of one or both of chromosomes Y and 1 or by structural rearrangement involving 11q12~q13. We report five renal oncocytomas with structural chromosomal rearrangements involving 11q13 with previously unreported partner chromosomes (namely, 1, 6, and 7). For two of the five cases, a t(6;11)(p21;q13) translocation was revealed; the others had t(1;11)(p13;q13), t(7;11)(q11.2;q13), and t(5;11)(q35; q13). Fluorescence in situ hybridization confirmed translocation of CCND1 at 11q13 to partner chromosomes 5, 6, and 7. Overexpression of cyclin D1, the protein product of CCND1, was detected in three of the five cases (60%) by means of immunohistochemical staining of formalin-fixed, paraffin-embedded tumor sections. In three cases for which fresh tissue was available, Southern blot analysis using the MDL-5 probe for the BCL1 breakpoint did not reveal rearrangement of BCL1. In addition, six consecutive renal oncocytomas diagnosed at our institution between 1999 and 2002 whose karyotypes did not show 11q13 translocations were all negative for cyclin D1 overexpression under immunohistochemical analysis. The findings of CCND1 rearrangement with FISH and correlation with cyclin D1 overexpression under immunohistochemical analysis suggest that cyclin D1 alterations play a role in the subset of renal oncocytomas with 11q translocations, although other genes may also be involved. [Copyright &y& Elsevier]