Intraductal papillary mucinous neoplasms of the pancreas: Clinical association with KRAS

Intraductal papillary mucinous neoplasms of the pancreas (IPMN) are among the most important precancerous lesions in the pancreas. V-Ki-ras 2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most important genes involved in pancreatic neoplasms, and exhibits a high mutation rate in pancreatic ductal adenocarcinomas and pancreatic intraepithelial neoplasia. The present study aimed to further elucidate the associations among IPMN subtypes (gastric, intestinal, pancreatobiliary and oncocytic), pathological classifications [low-grade, intermediate-grade, and high-grade IPMN, and associated minimally invasive carcinoma (invasive depth ≤0.5 cm) and advanced invasive carcinoma (invasive depth >0.5 cm)]. A total of 56 cases of IPMN were studied using scorpion amplified refractory mutation system analysis of KRAS mutations, pathological features and prognosis. KRAS mutations were identified in 50% (28/56 cases). The frequency was 60% (9/15 cases) in gastric-type, 52.6% (10/19 cases) in intestinal-type, 47.3% (9/19 cases) in pancreatobiliary-type and zero (0/3 cases) in oncocytic-type IPMN. Except for oncocytic type IPMN, the frequencies of KRAS mutations in IPMN with low, intermediate and high grade, and IPMN-associated carcinoma were 58.3% (7/12 cases), 27.3% (3/11 cases), 80% (4/5 cases) and 56% (14/25 cases), respectively. With more advanced dysplasia and invasion, the prevalence of KRAS mutations in intestinal-type IPMN increased (P=0.012). The Kaplan-Meier survival curve demonstrated that survival rate was not associated with KRAS mutation (log-rank test; P=0.308). The prevalence of KRAS mutations was lowest in intestinal-type IPMN, and was in proportion to the degree of dysplasia and invasion. Therefore, KRAS mutation in IPMN does not correlate with histological subtype, dysplasia grade, depth of invasion or survival.