title: Association of overexpression of TIF1γ with colorectal carcinogenesis and advanced colorectal adenocarcinoma.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Pathology, New York University School of Medicine, New York, NY 10016, United States.
authors: Shilpa
authors: S
authors: Jain
authors: Shashideep
authors: S
authors: Singhal
authors: Franto
authors: F
authors: Francis
authors: Cristina
authors: C
authors: Hajdu
authors: Jin-Hua
authors: JH
authors: Wang
authors: Arief
authors: A
authors: Suriawinata
authors: Yin-Quan
authors: YQ
authors: Wang
authors: Miao
authors: M
authors: Zhang
authors: Elizabeth H
authors: EH
authors: Weinshel
authors: Fritz
authors: F
authors: Francois
authors: Zhi-Heng
authors: ZH
authors: Pei
authors: Peng
authors: P
authors: Lee
authors: Ru-Liang
authors: RL
authors: Xu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D046228:Microarray Analysis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D051901:Smad4 Protein; C511956:TRIM33 protein, human; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II