Abstract 4943: Detection of specific KRAS mutation type, Gly12Asp (GGT&gt;GAT), in EUS-guided fine needle aspiration cytology (EUS-FNAC) identifies pancreatic cancer patients with poor prognosis
Authors: Minarik Marek , Halkova Tereza , Belsanova Barbora , Bunganic Bohus , Zavoral Miroslav , Benesova Lucie 
Published: July 2016

Background

Although the disease progression of pancreatic ductal adenocarcinoma (PDAC) is very rapid with median survival typically around 3 to 6 months, there are rare cases of patients remaining on therapy for longer periods of time. Early estimation of survival prognosis would allow for rational decisions on complex therapy interventions, including radical surgery and robust systemic therapy regimens. Understandably, there is a great interest in finding prognostic markers that can be used for patient stratification. KRAS, often mutated in PDAC, has been a frequent subject of studies in molecular pancreatic cancer research. It was reported early on that KRAS mutation detected in pancreatic mass itself does not show any prognostic value (1). In this work we have investigated role of various KRAS mutation types on the prognosis of pancreatic cancer patients. Similar to other types of solid tumors it is expected that different KRAS mutations will result in slightly different clinical outcome (2,3)

Methods

A total of 118 pacients with PDAC clinically confirmed by EUS-FNAC were included in the study. DNA was extracted from FNAB slides following a standard cytology evaluation to ensure adequacy (viability, quantity) and to mark tumor cell fraction. Kaplan-Meier survival curves were calculated for individual KRAS mutation types.

Results summary

KRAS mutation was detected in 90% of specimes (106/ 118). All mutations were localized at exon 2, codon 12 with Gly12Asp (GGT&gt;GAT) as the most frequent at 45% (48/106), followed by other types including Gly12Val (GGT&gt;GTT) at 31% (33/106), Gly12Arg (GGT&gt;CGT)at 17% (18/106), Gly12Cys (GGT/TGT) at 5% (5/106) and Gly12Ser (GGT/AGT) at 1% (1/106). Overall survival for patients with the Gly12Asp mutation was only 107 days, compared to 198 days for the Gly12Val, 286 days for Gly12Arg and 206 days for Gly12Cys (P = 0.01, long-rank test). Survival of patients with the Gly12Asp was less than a half when compared to all of the other mutation types combined (107 days vs. 218 days, P = 0.002, long-rank test).

Conclusions

The overall survival of PDAC patients correlates with the type of KRAS mutation present in the tumor. The most frequent Gly12Asp (GGT&gt;GAT) mutation confers the worst prognosis resulting in a reduction of survival typically by 3 - 6 months. KRAS testing from EUS-FNAC slides presents a useful tool for stratification of PDAC patients. Supported by IGA MZ grant no. NT13638.

Literature:

1) Salek C et al. Anticancer Res. 2009, 29, 1803-1810

2) Garassino MC, Ann Oncol, 2011, 22, 235-237

3) Fiala O et al., Cancer Genet., 2013, 206, 26-31.

Citation Format: Marek Minarik, Tereza Halkova, Barbora Belsanova, Bohus Bunganic, Miroslav Zavoral, Lucie Benesova. Detection of specific KRAS mutation type, Gly12Asp (GGT&gt;GAT), in EUS-guided fine needle aspiration cytology (EUS-FNAC) identifies pancreatic cancer patients with poor prognosis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4943.