Loss of Heterozygosity Predicts Poor Survival After Resection of Pancreatic Adenocarcinoma

Overview

Journal J Gastrointest Surg

Specialty Gastroenterology

Date 2008 Aug 5

PMID 18677542

Citations 14

Authors

Jan Franko

Alyssa M Krasinskas

Marina N Nikiforova

Narcis O Zarnescu

Kenneth K W Lee

Steven J Hughes

David L Bartlett

Herbert J Zeh 3rd

A James Moser

Affiliations

Soon will be listed here.

Abstract

Background: American Joint Committee on Cancer (AJCC) staging for pancreatic adenocarcinoma is a validated predictor of prognosis but insufficiently discriminates postresection survival. We hypothesized that genetic analysis of resected cancers would correlate with tumor biology and postoperative survival.

Methods: Resected pancreatic ductal and ampullary adenocarcinomas (n = 50) were analyzed for loss of heterozygosity (LOH) at 15 markers including 5q(APC), 6q(TBSP2), 9p(p16), 10q(PTEN), 12q(MDM2), 17p(TP53), and 18q(DCC/SMAD4). KRAS exon 1 mutations were detected by sequencing. The primary endpoint of this interim data analysis was survival at 18 month median follow-up.

Results: Negative margins were achieved in 43 (86%) cases. AJCC stage was: Ia/b (3), IIa (16), IIb (31). KRAS mutations were detected in 31 cases (62%) and LOH in 26 (52%) with mean fractional allelic loss score 23 +/- 16%. Median survival was significantly shorter with LOH (15.2 months versus not reached; p = 0.021) and KRAS mutations (19.6 months versus not reached; p = 0.038). Combining KRAS mutation with LOH was a powerful negative predictor in Cox regression (HR = 10.6, p = 0.006). Stage, nodal and margin status were not predictive of survival.

Conclusion: LOH and KRAS mutations indicate aggressive tumor biology and correlate strongly with survival in resected pancreatic ductal and ampullary carcinomas. Genetic analysis may improve risk stratification in future clinical trials.

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