K-ras-2 topographic genotyping of pancreatic adenocarcinoma
S. D. Finkelstein, R. Przygodzki, V. E. Pricolo, R. Sayegh, A. Bakker, P. A. Swalsky and G. Keller
Department of Pathology, Prebyterian University Hospital, University of Pittsburgh, Pa.
OBJECTIVE: To determine the frequency distribution of K-ras-2 point
mutation genotypes in pancreatic adenocarcinoma and to evaluate the
effectiveness of K-ras-2 genotyping as a means to predict localized disease
and potential long-term survival. DESIGN: Topographic genotyping from
archival formalin-fixed, paraffin-embedded large- and biopsy-sized tissue
specimens as well as cytologic fluid using polymerase chain reaction
products and direct sequencing together with clinicopathologic and
statistical analysis. SETTING: Tertiary care medical center with molecular
diagnostics pathology laboratory. PATIENTS: Patients treated between 1988
and 1993 at Rhode Island Hospital, Providence, yielding 55 primary and 56
metastatic specimens of pancreatic adenocarcinoma. RESULTS: Each primary
pancreatic adenocarcinoma was found to contain one of eight specific
genotypes that was maintained in all metastatic deposits of that individual
tumor. Primary adenocarcinomas confined to the pancreatic bed at diagnosis
were predominantly of a normal genotype (56% [14/25]). Pancreatic
adenocarcinomas progressing to distant hematogenous metastasis were almost
exclusively mutated (88% [7/8]; P < .005). Patients undergoing
pancreatic resection (Whipple's operation) and having a normal
K-ras-2-genotype (58% [11/19]) had a significantly longer survival (21.3
months) than similar patients with mutated tumors (8.2 months).
CONCLUSIONS: The findings support the feasibility of K-ras-2 topographic
genotyping to identify potentially indolent disease and suggest a
potentially useful role in the preoperative evaluation of pancreatic
adenocarcinoma.
