Differences in TGF-β1 signaling and clinicopathologic characteristics of histologic subtypes of gastric cancer

BMC Cancer

Research Article

Dong Hoon Kim¹  Hyunki Kim²  Kyung Ho Pak³  Do Hyung Lee⁴  Jae-Ho Cheong⁵ 

[1] Department of Pathology, Hallym University Medical Center, Hwasung, Korea;Department of Pathology, Yonsei University College of Medicine, Seoul, Korea;Department of Surgery, Hallym University Medical Center, Hwasung, Korea;Department of Medicine, Yonsei University Graduate School, Seoul, Korea;Depatment of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, 120-752, Seodaemun-gu, Seoul, Korea;Depatment of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, 120-752, Seodaemun-gu, Seoul, Korea;Department of Biochemistry & Molecular Biology, Yonsei University College of Medicine, Seoul, Korea;Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea;Open NBI Convergence Technology Research Laboratory, Yonsei University College of Medicine, Seoul, Korea;

关键词: TGF-β1;    Lauren classification;    Gastric cancer;   

DOI  :  10.1186/s12885-016-2091-x

 received in 2015-08-05, accepted in 2016-01-28,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundAberrant TGF-β1 signaling is suggested to be involved in gastric carcinogenesis. However, the role of TGF-β1 in intestinal-type [i-GC] and diffuse-type [d-GC] gastric cancer remains largely unknown. In this study, we evaluated the expression of TGF-β1 signaling molecules and compared the clinicopathological features of i-GC and d-GC.MethodsPatients (n=365, consecutive) who underwent curative gastrectomy for gastric adenocarcinoma in 2005 were enrolled. We performed immunohistochemical staining of TGF-β1, TGF-β1 receptor-2 (TβR2), Smad4, p-ERK1/2, TGF-activated kinase (TAK)1, and p-Akt in 68 paraffin-embedded tumor blocks (33 i-GC and 35 d-GC), scored the expression according to the extent of staining, and evaluated differences between the histologic subtypes.ResultsPatients with d-GC differed from those with i-GC as follows: younger and more likely to be female; more aggressive stage; higher recurrence rate. The expression of TGF-β1 and TβR2 was higher in i-GC (P = 0.05 and P <0.001, respectively). The expression of Smad4, a representative molecule of the Smad-dependent pathway, was decreased in both subtypes. TAK1 and p-Akt, two major molecules involved in the Smad-independent pathway, were over-expressed (69 ~ 87 % of cases stained), without a statistically significant difference between i-GC and d-GC. Of note, the expression of p-ERK1/2, a Smad-independent pathway, was significantly increased in i-GC (P = 0.008).ConclusionsThe clinicopathological characteristics vary in different histologic gastric cancer subtypes. Although TGF-β1 signaling in gastric cancer cells appears hyper-activated in i-GC compared to d-GC, the Smad-dependent pathway seems down-regulated while the Smad-independent pathway seems up-regulated in both histologic subtypes.

【 授权许可】

CC BY   
© Pak et al. 2016