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SANGER SEQUENCING IN ROUTINE KRAS TESTING: AREVIEW OF 1720 CASES FROM A PATHOLOGIST’SPERSPECTIVE

By Umberto Malapelle, Claudio Bellevicine, Maria Salatiello, Caterina De Luca, Elisabetta Rispo, Palmira Riccio, Lucianna Sparano, Alfonso De Stefano, Chiara Carlomagno, Franceso Maiello, Giulia Vita, Osar Nappi and Giancarlo Troncone

Abstract

BACKGROUND. Sanger sequencing (SS) of PCR products is still the most frequent method to test colorectal cancer for KRAS mutations in routine practice. METHODS. An audit of SS on 1720 routine cases was carried out, taking into account age, gender, specimen type (resection vs biopsies), tumour site (primary vs metastasis), tumour stage, neoplastic cells abundance (>30% vs <30%) and fixation type (buffered formalin vs simple formalin). In a subset of 50 wild-type (WT) patients correlations between SS findings and response rate (RR), progression-free survival (PFS) and overall survival (OS) were also evaluated. RESULTS. The tests were informative in 1691 cases (98,3%). Mutations were detected in 671 cases (39,6%). No significant differences in mutation rates were observed respect to age (p=0.2), gender (p=0.2), specimen type (p=0.3) and formalin fixation (p=0.08). Conversely, KRAS mutant rate was higher in metastatic tissue (50% vs 39%: p=0.02), in sample with >30% of neoplastic cells (43,4% vs 26,6% p=0.02) and in tumours tested in stage IV (p=0.05). The RR of SS KRAS-WT patients was 26% (1 complete and 12 partial responses). The disease control rate (objective responses plus stable disease), was 56%. However, median PFS was 4.4 months and the median OS was 10.4 months. CONCLUSIONS. Pathological criteria that make SS a more robust method for KRAS testing and treatment responseprediction are neoplastic cell abundance, metastatic tissue sample and stage IV primary tumor

Topics: COLORECTAL CANCER, AUDIT, HISTOPATHOLOGY, LABORATORY TESTS, MOLECULAR PATHOLOGY
Publisher: 'BMJ'
Year: 2012
DOI identifier: 10.1136/jclinpath-2012-200773
OAI identifier: oai:www.iris.unina.it:11588/457773
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