KRAS Mutation Analysis on Cytological Specimens of Metastatic Colo-Rectal Cancer

Recent evidences showed that metastatic colorectal cancer (CRC) patients with tumors harboring a KRAS gene mutation do not derive benefit from the administration of epidermal growth factor receptor-directed monoclonal antibodies. Typically, the specimens available for KRAS mutational analysis are formalin-fixed paraffin- embedded (FFPE) primary tumor tissue blocks. However, in patients with rectal tumours undergoing neoadjuvant therapy, the source of FFPE material is limited. In this setting, CRC cytological samples taken from the metastatic site may be exploited. However, these specimens show at least some degree of necrosis; thus, their suitability for the KRAS assay needs to be tested. Here, we show that 18/19 (94.7%) metastatic CRC smears were perfectly adequate for codon 12 and 13 KRAS mutational analysis by direct gene sequencing. Only one case (5.3%) showing abundant necrotic debris and poor cellular preservation was not informative for KRAS status. Codon 12 gene mutations were found in 4/18 (22.2%) of the adequate cases (c35G>T n = 2; c34G>T n = 1; c35G>A n - 1). Concordance between cytological and FFPE samples, both available in 13 patients, occurred in 92.3% (12/13) of the cases. Thus, whenever histological specimens of CRC are not available, KRAS testing may be reliably performed on cytological specimens. Diagn. Cytopathol. 2010;38:869-873. (C) 2010 Wiley-Liss, Inc.