TY - JOUR
T1 - Association of overexpression of TIF1γ with colorectal carcinogenesis and advanced colorectal adenocarcinoma
AU - Jain, Shilpa
AU - Singhal, Shashideep
AU - Francis, Franto
AU - Hajdu, Cristina
AU - Wang, Jin Hua
AU - Suriawinata, Arief
AU - Wang, Yin Quan
AU - Zhang, Miao
AU - Weinshel, Elizabeth H.
AU - Francois, Fritz
AU - Pei, Zhi Heng
AU - Lee, Peng
AU - Xu, Ru Liang
PY - 2011/9/21
Y1 - 2011/9/21
N2 - 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 archiival 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 TGFβR. 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 TGFβR 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.
AB - 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 archiival 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 TGFβR. 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 TGFβR 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.
KW - Colorectal cancer
KW - Smad4
KW - Transcriptional intermediary factor 1 gamma
KW - Transforming growth factor-beta signaling pathway
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U2 - 10.3748/wjg.v17.i35.3994
DO - 10.3748/wjg.v17.i35.3994
M3 - Article
C2 - 22046087
AN - SCOPUS:80054865985
SN - 1007-9327
VL - 17
SP - 3994
EP - 4000
JO - World journal of gastroenterology
JF - World journal of gastroenterology
IS - 35
ER -
