Abstract 539: Usefulness of genetic markers in pancreatic juice for the diagnosis of pancreatic cancer distinguishing from chronic inflammation: A meta-analysis

Abstract

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) shows frequent genomic alterations in the 4 major genes, KRAS, CDKN2A/p16, TP53, and SMAD4/DPC4. Furthermore, a recent high-sensitivity mutational analysis discovered KRAS mutations in over 90% of pancreatic intraepithelial neoplasms. The genomic alterations of those genes in the pancreatic juice (PJ) have been studied for the early detection of PDAC, but the results were heterogeneous and its application was limited mainly because of the low diagnostic specificity; KRAS gene mutations have been also detected in chronic pancreatitis (CP). Therefore, for the diagnosis of early pancreatic cancer distinguishing from CP using PJ samples, more sensitive and specific method should be developed. Objective: To evaluate the diagnostic accuracy of the genetic or molecular markers in PJ samples distinguishing PDAC from CP, which is associated with a risk of pancreatic cancer development. Methods: We conducted a quantitative meta-analysis of the diagnostic studies using PJ samples, and validated the diagnostic utility of the 4 major genes, the telomerase activity, and combination assays. A systematic search of all relevant literature was performed in MEDLINE, Cochrane Database, and Web of Science. Quality assessment was conducted by adopting the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist. Data are presented as forest plots and hierarchical summary receiver operating characteristic curve analysis was used to summarize the overall test performance. Results: Thirty-nine studies fulfilled the inclusion criteria, and data were pooled for the analysis. Pooled estimates for the KRAS analysis were as follows: sensitivity 0.67 (95% CI: 0.63-0.71); specificity 0.82 (95% CI: 0.79-0.85); diagnostic odds ratio (DOR) 9.24 (95% CI: 6.00-14.23). Pooled estimates for the telomerase activity analysis were: sensitivity 0.82 (95% CI: 0.76-0.87); specificity 0.96 (95% CI: 0.90-0.99); DOR 54.38 (95% CI: 21.80-135.66). All 3 tumor suppressor genes, TP53, CDKN2A/p16, and SMAD4/DPC4, demonstrated low sensitivity. The combined analysis of KRAS with telomerase activity revealed higher diagnostic sensitivity (0.94, 95% CI: 0.83-0.99) than KRAS alone. The combined assay of telomerase activity with cytology revealed more reliable diagnosis of PDAC than telomerase activity alone with respect to sensitivity (0.88, 95% CI: 0.74-0.96) and specificity (1.00, 95% CI: 0.91-1.00). Conclusion: The most reliable marker for the diagnosis of PDAC in PJ samples was telomerase activity. The assessment by each 3 major tumor suppressor was not unsatisfactory. Telomerase activity can play a central role in diagnostic analysis using PJ samples, and combination assays with KRAS mutations or cytological examination would increase diagnostic accuracy. Citation Format: Tatsuo Hata, Masaharu Ishida, Fuyuhiko Motoi, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Michiaki Unno. Usefulness of genetic markers in pancreatic juice for the diagnosis of pancreatic cancer distinguishing from chronic inflammation: A meta-analysis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 539. doi:10.1158/1538-7445.AM2015-539