Reply to Jérôme Verine, Christophe Leboeuf and Philippe Ratajczak's Letter to the Editor re: Jimsgene Sanjmyatav, Sven Hauke, Mieczyslaw Gajda, et al. Establishment of a Multicolour Fluorescence In Situ Hybridisation-based Assay for Subtyping of Renal Cell Tumours. Eur Urol 2013;64:689–91

Abstract

We appreciate the comments by Verine and colleagues regarding our paper [1]. The authors correctly state that a recent online survey by the International Society of Urological Pathology (ISUP) demonstrated that fluorescence in situ hybridization (FISH) is not commonly used in the diagnostic algorithms of practicing pathologists [2]. However, wewould conclude that this fact underscores the need to prove the impact of genetic analysis based on FISH tests, as we performed in our study. Does FISH help to overcome the limitations of pathologic classification? Because the paper was accepted as a short communication, it was impossible to present detailed data of our FISH results in each tumor sample. In our retrospective validation study, we used cases with unequivocal histopathologic diagnosis. As we discussed in the paper, it is especially useful to identify specific genetic alterations to distinguish poorly differentiated clear cell renal cell carcinoma (RCC) from variants of papillary type 2 RCC. Although there was a genetic overlap between these entities, a clear diagnosis could be made in the majority of cases on the basis of our FISH analysis. An overlap was also found between chromophobe RCC and oncocytomas. Histologically defined chromophobe RCCs were correctly identified based on FISH. In some oncocytomas, however, multiple chromosomal losses were detected in small numbers of cell nuclei in contrast to chromophobe RCCs, with >50% of altered nuclei per tumor. The oncocytomas with several chromosomal losses were independently evaluated by three pathologists, showing some interobserver variability in the classification of such tumors with equivocal FISH results. Further studies are necessary to characterize this specific subgroup of oncocytomas, which seems to be in a close relationshipwith chromophobe RCC. At the Vancouver ISUP conference, consensus was that such hybrid oncocytic chromophobe tumors should be placed, for the time being, in the chromophobe RCC category [3].