title: Differences in TGF-β1 signaling and clinicopathologic characteristics of histologic subtypes of gastric cancer.
abstract: Aberrant 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.
  
  
  
  Patients (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.
  
  
  
  Patients 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).
  
  
  
  The 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.
authors: Department of Surgery, Hallym University Medical Center, Hwasung, Korea. sweetpkh@gmail.com.|Department of Medicine, Yonsei University Graduate School, Seoul, Korea. sweetpkh@gmail.com.
authors: Kyung Ho
authors: KH
authors: Pak
authors: Department of Pathology, Hallym University Medical Center, Hwasung, Korea. homed@hallym.or.kr.
authors: Dong Hoon
authors: DH
authors: Kim
authors: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea. kimhyunki@yuhs.ac.
authors: Hyunki
authors: H
authors: Kim
authors: Depatment of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, 120-752, Seoul, Korea. dhlee5285@daum.net.
authors: Do Hyung
authors: DH
authors: Lee
authors: Depatment of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, 120-752, Seoul, Korea. jhcheong@yuhs.ac.|Department of Biochemistry & Molecular Biology, Yonsei University College of Medicine, Seoul, Korea. jhcheong@yuhs.ac.|Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. jhcheong@yuhs.ac.|Open NBI Convergence Technology Research Laboratory, Yonsei University College of Medicine, Seoul, Korea. jhcheong@yuhs.ac.
authors: Jae-Ho
authors: JH
authors: Cheong
mesh_terms: D000368:Aged; D051017:Apoptosis Regulatory Proteins; D063646:Carcinogenesis / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D053773:Transforming Growth Factor beta1