Mucinous cystic neoplasms of the liver and pancreas: relationship between KRAS driver mutations and disease progression

被引：23

作者：

Fujikura, Kohei ^{[1
]}

Akita, Masayuki ^{[1
]}

Abe-Suzuki, Shiho ^{[1
]}

Itoh, Tomoo ^{[1
]}

Zen, Yoh ^{[1
]}

机构：

[1] Kobe Univ, Grad Sch Med, Dept Diagnost Pathol, Kobe, Hyogo 6500017, Japan

来源：

HISTOPATHOLOGY | 2017年 / 71卷 / 04期

关键词：

driver mutation; KRAS; liver; mucinous cystic neoplasm; pancreas; INTRADUCTAL PAPILLARY NEOPLASMS; K-RAS MUTATIONS; BILE-DUCT; SEQUENTIAL ACCUMULATION; P53; OVEREXPRESSION; DIAGNOSIS; CANCER; MALIGNANCY; MANAGEMENT; FEATURES;

D O I：

10.1111/his.13271

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Aims: To compare the oncogenic mutation status among mucinous cystic neoplasms (MCNs) of different histological grades and between liver and pancreatic MCNs. Methods and results: KRAS, GNAS, RNF43 and PIK3CA were sequenced in 25 surgical cases of hepatopancreatic MCN. Molecular features were correlated with clinicopathological and immunohistochemical findings. KRAS mutations were identified in five cases (20%), whereas GNAS, RNF43 and PIK3CA were wild-type in all cases. KRAS mutations were uncommon in cases of low-grade dysplasia (1/20, 5%), whereas KRAS was mutated in all cases of higher grades, except for one liver MCN with intermediate-grade dysplasia (4/5, 80%; P = 0.002). This genetic alteration was slightly more frequent in the pancreas than in the liver [4/17 (24%) versus 1/8 (13%), P = not significant]. KRAS-mutated MCNs more commonly had a multilocular cystic appearance (P = 0.040) and expression of mucin (MUC) 1 (P = 0.040), MUC2 (P = 0.016) and MUC5AC (P = 0.015) than KRAS-wild-type tumours. In cases of KRAS-mutated MCNs with intermediate-grade or high-grade dysplasia, identical mutations were also detected in areas of adjacent low-grade dysplasia. Conclusions: KRAS mutations appear to be major driver genetic alterations in both liver and pancreatic MCNs. As identical KRAS mutations were present in low-grade and higher-grade areas in individual cases, KRAS mutations occurring in low-grade MCNs may lead to tumour progression. Thus, preoperative KRAS testing may contribute to estimations of malignant potential. The lower incidence of KRAS mutations in liver MCNs may also explain why the risk of malignant transformation in liver MCNs is lower than that in pancreatic MCNs.

引用

页码：591 / 600

页数：10

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