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01-10-2008 | ssat plerery presentation

Loss of Heterozygosity Predicts Poor Survival After Resection of Pancreatic Adenocarcinoma

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 III, A. James Moser

Published in: Journal of Gastrointestinal Surgery | Issue 10/2008

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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Title: Loss of Heterozygosity Predicts Poor Survival After Resection of Pancreatic Adenocarcinoma
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 III
A. James Moser
Publication date: 01-10-2008
Publisher: Springer-Verlag
Published in: Journal of Gastrointestinal Surgery / Issue 10/2008
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-008-0577-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Loss of Heterozygosity Predicts Poor Survival After Resection of Pancreatic Adenocarcinoma

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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