Extensive alteration in the expression profiles of TGFB pathway signaling components and TP53 is observed along the gastric dysplasia-carcinoma sequence.
The expression patterns of TGFB signaling proteins, such as TGFB1/2, TGFBR1(ALK5), TGFBR2, SMAD1/2/3, SMAD2/3, SMAD4, SMAD7, and of downstream targets of TGFB signaling, CDKN1A (p21CIP1), CDKN1B (p27KIP1), MYC, CDC25A, TP53, and RELA (p65NF-kB) were investigated in gastric carcinomas and other gastric lesions.



A total of 112 gastric carcinomas, 37 dysplasias, 54 intestinal metaplasias, 29 chronic atrophic gastritis and 54 normal gastric epithelium were analyzed by tissue microarray-based immunohistochemical analysis. Extensive changes in expression profiles of these proteins were observed. Three types of expression patterns were observed along the normal epithelium-atrophic gastritis-dysplasia-carcinoma sequence. (1) Expression of TGFB1/2, TGFBR1, MYC, and TP53 continually increased along this sequence. (2) Expression of SMAD4, CDKN1A, SMAD1/2/3, SMAD2/3, and CDKN1B was enhanced in dysplasia but decreased in carcinoma. (3) Expression of TGFBR2, SMAD7, RELA, and CDC25A was enhanced in dysplasia and the enhanced level was maintained in carcinoma. In addition, we also evaluated the clinical significance of the expression of TGFB signaling proteins in gastric carcinoma. TGFB and MYC were positively correlated with advanced stages, whereas SMAD1/2/3 and SMAD4 were strongly associated with earlier stages.



The extensive change in expression of TGFB signaling components is implicated during tumorigenesis of gastric neoplasias.
Kim
Seok-Hyung
SH
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Lee
Seung-Hyun
SH
Choi
Yoon-La
YL
Wang
Li-Hui
LH
Park
Cheol Keun
CK
Shin
Young Kee
YK
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C495901:TP53 protein, human; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53