Association of overexpression of TIF1γ with colorectal carcinogenesis and advanced colorectal adenocarcinoma

• Published in: World journal of gastroenterology : WJG Vol. 17; no. 35; pp. 3994 - 4000
• Main Authors: Jain, Shilpa, Singhal, Shashideep, Francis, Franto, Hajdu, Cristina, Wang, Jin-Hua, Suriawinata, Arief, Wang, Yin-Quan, Zhang, Miao, Weinshel, Elizabeth H, Francois, Fritz, Pei, Zhi-Heng, Lee, Peng, Xu, Ru-Liang
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Co., Limited 21-09-2011
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Brief; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Humans; Microarray Analysis; Protein-Serine-Threonine Kinases - metabolism; Receptors, Transforming Growth Factor beta - metabolism; Smad4; Smad4 Protein - metabolism; Transcription Factors - metabolism; 免疫组织化学; 协会; 大肠癌; 石蜡包埋组织; 腺癌; 转化生长因子-β; 过度表达; Transcriptional intermediary factor 1 gamma; Smad4; Colorectal cancer; Transforming growth factor-beta signaling pathway
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v17.i35.3994

AIM：To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma （TIF1γ）,Smad4 and transforming growth factor-beta （TGFβR） across a spectrum representing colorectal cancer （CRC） development.METHODS：Tissue microarrays were prepared from archival paraffin embedded tissue,including 51 colorectal carcinomas,25 tubular adenomas （TA） and 26 HPs,each with matched normal colonic epithelium.Immunohistochemistry was performed using antibodies against TIF1γ,Smad4 and TGFβ RⅡ.The levels of expression were scored semi-quantitatively （score 0-3 or loss and retention for Smad4）.RESULTS：Overexpression of TIF1γ was detected in 5/26 （19%） HP;however,it was seen in a significantly higher proportion of neoplasms,15/25 （60%） TAs and 24/51 （47%） CRCs （P0.05）.Normal colonic mucosa,HP,and TAs showed strong Smad4 expression,while its expression was absent in 22/51 （43%） CRCs.Over- expression of TGFβ RⅡ was more commonly seen in neoplasms,13/25 （52%） TAs and 29/51 （57%） CRCs compared to 9/26 （35%） HP （P0.05）.Furthermore,there was a correlation between TIF1γ overexpression and Smad4 loss in CRC （Kendall tau rank correlation value=0.35,P0.05）.The levels of TIF1γ overexpression were significantly higher in stage Ⅲ than in stage Ⅰ and Ⅱ CRC （P0.05）.CONCLUSION：The findings suggest that over-expression of TIF1γ occurs in early stages of colorectal carcinogenesis,is inversely related with Smad4 loss,and may be a prognostic indicator for poor outcome.