Details

Autor(en) / Beteiligte

• Mohri, Dai
• Asaoka, Yoshinari
• Ijichi, Hideaki
• Miyabayashi, Koji
• Kudo, Yotaro
• Seto, Motoko
• Ohta, Miki
• Tada, Motohisa
• Tanaka, Yasuo
• Ikenoue, Tsuneo
• Tateishi, Keisuke
• Isayama, Hiroyuki
• Kanai, Fumihiko
• Fukushima, Noriyoshi
• Tada, Minoru
• Kawabe, Takao
• Omata, Masao
• Koike, Kazuhiko

Titel

Different subtypes of intraductal papillary mucinous neoplasm in the pancreas have distinct pathways to pancreatic cancer progression

Ist Teil von

• Journal of gastroenterology, 2012-02, Vol.47 (2), p.203-213

Ort / Verlag

Japan: Springer Japan

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Springer LINK 全文期刊数据库

Beschreibungen/Notizen

• Background Intraductal papillary mucinous neoplasm (IPMN) is recognized as a precursor lesion to pancreatic cancer, a unique pathological entity. IPMN has subtypes with different clinical characteristics. However, the molecular mechanisms of cancer progression from IPMN remain largely unknown. In this study we examined the differences in genetic alteration(s) among the IPMN subtypes. Methods Surgically resected IPMNs ( n  = 25) were classified into four subtypes by hematoxylin and eosin (H&E) and mucin immunostaining. Mutations in KRAS , BRAF , and PIK3CA genes and expression of CDKN2A, TP53, SMAD4, phospho-ERK, and phospho-SMAD1/5/8 proteins were examined. Results There were 11 gastric, 11 intestinal, one pancreatobiliary, and two oncocytic types in this study. We then compared the two major subtypes, gastric-type and intestinal-type IPMN. Gastric-type IPMN showed a significantly higher incidence of KRAS mutations (9/11, 81.8%) compared with intestinal type (3/11, 27.3%; p  < 0.05), although the intestinal type showed a higher grade of dysplasia than gastric type ( p  < 0.01). All cases with KRAS mutations showed phospho-ERK immunostaining. In contrast, intestinal type (9/11, 81.8%) showed more frequent SMAD1/5/8 phosphorylation compared with gastric-type IPMN (3/11, 27.3%; p  < 0.05%). Conclusions There may be distinct mechanisms of pancreatic cancer progression in the different subtypes of IPMN. In particular, KRAS mutation and bone morphogenetic protein-SMAD signaling status may be crucial diverging steps for the two representative pathways to pancreatic cancer in IPMN patients.