Abstract 3348: Immunophenotyping, xenotransplantability and molecular cytogenetic features of the sarcomatoid renal carcinoma cell line RCC52: Pathobiological significance

Abstract

Abstract The immunobiology of sarcomatoid renal cell carcinoma (RCC) and how it has been transformed or progressed from clear cell-RCC are currently poorly understood. We analyzed a sarcomatoid renal carcinoma cell line (RCC52) derived from a primary clear cell renal carcinoma with intensive sarcomatoid differentiation, with respect to its immunophenotyping, molecular cytogenetic features and xenotransplantability. RCC52 cells grown as monolayers consisted of mostly small-sized epithelioid cells along with a small proportion of spindle/fibroblast-like cells, suggestive of growth of the sarcomatoid, but not clear cell component of the tumor. Cytofluorometric analysis revealed a phenotype of cell surface HLA-I−, E-CDH−, N-CDH−, EpCAM−, CD44+, CD54+, CD58+, URO1+ and URO10+ and cytoplasmic AE1+, E-CDH−, N-CDH+, Vimentin+, S100+ and VEGF+. Spectral karyotyping (SKY) show the chromosomal abnormalities in 22 metaphases examined to be 40-42<2n>,X,-Y[22]; der(2)t(2,3)(q35;q21)[20]; der(14)(14;17)(p11;q12)[22]; −3[11]; +7,+7[14]; −14[9]; −15[14]; −10[10]; −22[16]. Numerical imbalances were also assessed by comparative genomic hybridization, which are found to be consistent with the findings determined by banding and SKY. These results along with the documented genotype have established the identity of the RCC52 cell lines. Nude mouse xenografts resulting from RCC52 cell s.c. injection and the original tumor shared similar histopathology with mostly sarcomatoid elements with occasional clear cell areas, suggesting malignant potential of this cell line and the capability of sarcomatoid RCC cells to undergo transdifferentiation or dedifferentiation. The total HLA class I loss caused by the two distinctive mutations in the β2-microglobulin gene and loss of heterozygosity (LOH) in chromosome 15 observed recently (Cancer ImmunoI Immunother, 58:395-408, 2009) did not prevent sarcomatoid RCC52 cells from undergoing such transdifferentiation. Overall our results is of immunological (evasion of the host immunosurveillance) and pathobiological (progression/differentiation/transdifferentiation) significance, which forms the basis of further investigations with additional cell lines/ clones and tissues of clear cell-RCCs with sarcomatoid differentiation to confirm (i) loss HLA class I expression in most, if not all, sarcomatoid RCCs, and (ii) the proposed sequence of clear cell-RCC → fibroblast-like sarcomatoid RCC → epithelioid sarcomatoid RCC, which could in turn transdifferentiate into clear cell-RCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3348.