40. Correlation of histology, CCND1 over-expression, and CCND1 rearrangement in Renal Cell Carcinomas

      Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, comprising approximately 3% of all adult malignancies and 90-95% of neoplasms derived from the kidney. RCCs can be sporadic or associated with genetic syndromes. RCCs are categorized into subtypes according to the 2016 WHO system: clear cell, papillary, chromophobe, emerging/provisional, and unclassified RCCs. Accurate classification of RCCs is essential for appropriate clinical management and prognosis prediction. RCCs are classified by molecular and histopathological subtypes, but some renal tumors are diagnostically challenging due to having a combination of features that are characteristic of different subtypes. Classification also may be complicated by the presence of significant intra-tumoral genetic heterogeneity. There are greater than 10+ molecular and histopathological subtypes, likely prompting further RCC classification revision due to advances in morphological and molecular characterizations of renal tumors. For the morphologically similar chromophobe RCC subtype and benign renal oncocytoma (RO), currently, there are no widely-accepted immunohistochemical (IHC) or fluorescence in situ hybridization (FISH) markers that are used clinically to distinguish between the two. Cytogenetically, chromophobe RCCs can exhibit a hypodiploid karyotype, with losses of chromosomes 1, 2, 6, 10, 13, 17, and 21,+/-Y, in addition to deletions in 9p21.3. In contrast, benign RO can display a diploid karyotype, losses of chromosomes 1, Y, 14 or rearrangement of 11q13, including the CCND1 gene. Therefore, evaluating the over-expression of CCND1 protein by IHC with concurrent CCND1 rearrangement by FISH could guide the differential of chromophobe from benign RO, helping resolve and reduce unnecessary treatment. In this retrospective study, we assessed the potential correlative value of CCND1 over-expression by IHC and concurrent CCND1 gene rearrangement by FISH using a tissue microarray (TMA) prepared from histologically confirmed RCCs. A summary of the results will be presented.
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