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©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
Association of overexpression of TIF1γ with colorectal carcinogenesis and advanced colorectal adenocarcinoma
Shilpa Jain, Shashideep Singhal, Franto Francis, Cristina Hajdu, Jin-Hua Wang, Arief Suriawinata, Yin-Quan Wang, Miao Zhang, Elizabeth H Weinshel, Fritz Francois, Zhi-Heng Pei, Peng Lee, Ru-Liang Xu
Shilpa Jain, Franto Francis, Cristina Hajdu, Miao Zhang, Zhi-Heng Pei, Ru-Liang Xu, Department of Pathology, New York University School of Medicine, New York, NY 10016, United States
Shashideep Singhal, Department of Medicine, The Brooklyn Hospital Center, Brooklyn, NY 11201, United States
Arief Suriawinata, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, United States
Jin-Hua Wang, NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, United States
Yin-Quan Wang, Department of General Surgery, the First Hospital of Shanxi Medical University, 030001 Taiyuan, Shanxi Province, China
Elizabeth H Weinshel, Fritz Francois, Department of Medicine, New York University School of Medicine, New York, NY 10016, United States
Peng Lee, NYU Cancer Institute, New York University School of Medicine, and New York Harbor Healthcare System, New York, NY 10016, United States
Author contributions: Jain S, Singhal S, Francis F, Hajdu C, Wang JH, Suriawinata A, Wang YQ, Zhang M, Lee P and Xu RL performed the study and wrote the manuscript; Weinshel EH, Francois F, Pei ZH participated in manuscript preparation and /or research design.
Supported by Department of Pathology Research Fund, NYU School of Medicine, New York, NY 10016, United States
Correspondence to: Ru-Liang Xu, MD, PhD, Department of Pathology, New York University School of Medicine, 560 First Avenue, New York, NY 10593, United States.
ruliang.xu@nyumc.org
Telephone: +1-212-2630728 Fax: +1-212-2637916
Received: December 16, 2010
Revised: January 11, 2011
Accepted: January 18, 2011
Published online: September 21, 2011
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 TGFβRII. 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 (P < 0.05). Normal colonic mucosa, HP, and TAs showed strong Smad4 expression, while its expression was absent in 22/51 (43%) CRCs. Overexpression of TGFβRII was more commonly seen in neoplasms, 13/25 (52%) TAs and 29/51 (57%) CRCs compared to 9/26 (35%) HP (P < 0.05). Furthermore, there was a correlation between TIF1γ overexpression and Smad4 loss in CRC (Kendall tau rank correlation value = 0.35, P < 0.05). The levels of TIF1γ overexpression were significantly higher in stage III than in stage I and II CRC (P < 0.05).
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.
