ITF-2B protein levels are correlated with favorable prognosis in patients with colorectal carcinomas.
The majority of sporadic forms of colorectal carcinomas is characterized by deregulation of Wnt/β-catenin signaling early in colorectal carcinogenesis. As a consequence, ITF-2B protein levels are increased in adenomas of these patients. However, ITF-2B protein levels are strongly reduced with increasing carcinoma stages, suggesting that reduction of ITF-2B protein is required for progression of adenomas to colorectal carcinomas. To find out if ITF-2B protein levels are correlated with the survival of patients with colorectal carcinomas, a tissue microarray containing samples from 213 colorectal carcinomas (T-categories T2 and T3) with corresponding survival information was stained with an ITF-2B antibody. In addition, we analyzed if detection of ITF-2B in microsatellite instable and microsatellite stable carcinomas as well as in colorectal carcinomas with KRAS mutations is correlated with survival. Detection of cytoplasmic ITF-2B protein was associated with better overall and progression free survival of patients with colorectal carcinomas (P=0.033 and 0.024, respectively). Multivariate Cox regression analysis revealed an increased risk to suffer from poor overall survival and recurrent disease if no cytoplasmic ITF-2B was detectable (HR=1.91; P=0.033 and HR=1.75; P=0.033, respectively). Similarly, patients with MSS carcinomas had a better overall survival, if they showed cytoplasmic positivity for ITF-2B (P=0.013). Remarkably, patients with colorectal carcinomas carrying KRAS mutations had a better overall and progression free survival rate if the carcinomas were positive for cytoplasmic ITF-2B (HR=4.71; P=0.002 and HR=2.57; P=0.024, respectively). These data suggest that cytoplasmic protein levels of ITF-2B could be used as a prognostic marker for patients with colorectal carcinomas.
Department of Pathology, University of Munich D-80337 Munich, Germany.
Lydia
L
Brandl
Department of Pathology, University of Munich D-80337 Munich, Germany.
David
D
Horst
Department of Medicine II, University of Munich D-81377 Munich, Germany.
Enrico
E
de Toni
Department of Pathology, University of Munich D-80337 Munich, Germany ; German Cancer Consortium (DKTK) Im Neuenheimer Feld 280, 69120 Heidelberg, Germany ; German Cancer Research Center (DKFZ) Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Thomas
T
Kirchner
Department of Medicine II, University of Munich D-81377 Munich, Germany.
Andreas
A
Herbst
Department of Medicine II, University of Munich D-81377 Munich, Germany ; German Cancer Consortium (DKTK) Im Neuenheimer Feld 280, 69120 Heidelberg, Germany ; German Cancer Research Center (DKFZ) Im Neuenheimer Feld 280, 69120 Heidelberg, Germany ; Department of Internal Medicine and Gastroenterology, HELIOS Klinikum Berlin-Buch D-13125 Berlin, Germany.
Frank T
FT
Kolligs
CIN; ITF2; KRAS; MSI; MSS; colorectal carcinomas; prognosis