Profiling markers of prognosis in colorectal cancer.

Abstract

Purpose: Colorectal cancer is one of the most common forms of cancer in developed nations and the incidence of this disease is increasing. There is a need to further stratify prognostically distinct groups of colorectal cancer, and the purpose of this study was to identify prognostically significant immunohistochemical marker profiles in colorectal cancer. Experimental Design: In this study, a range (n = 23) of markers [pRb, p16, p21, p27, p53, proliferating cell nuclear antigen, cyclin D1, bcl-2, epidermal growth factor receptor, C-erb-B2, topoisomerase-I, liver fatty acid^binding protein, matrix metalloproteinases (MMP) 1-3, 7, 9, and 13, MT1-MMP, MT2-MMP, and tissue inhibitors of MMP 1-3] of putative prognostic significance have been investigated by immunohistochemistry on formalin-fixed, wax-embedded sections in a series (n = 90) of stage III (Dukes C) colorectal cancers. An immunohistochemical score based on the intensity of immunoreactivity and, where relevant, the proportion of immunoreactive cells was established for each marker. Results: Unsupervised two-dimensional hierarchical cluster analysis identified three distinct cluster groups (designated groups 1-3) with different marker profiles. There were significant survival differences between groups 1and 2 (log rank = 11.48; P = 0.0007) and between groups 1and 3 (log rank = 8.32; P = 0.0039). Multivariate analysis showed that the complete marker profile was independently the most significant prognostic factor (hazard ratio, 2.27; 95 % confidence interval, 1.15-4.48; P = 0.004). Conclusions: This study has identified an immunohistochemical marker profile of colorectal cancer and showed that it is an independent indicator of prognosis in this type of cancer.

Combination of p53 expression and p21 loss has an independent prognostic impact on sporadic colorectal cancer

“…In our study, patients with p53 expression had a better overall survival (p=0.048) which is in line with previous studies (9,22,23). These studies partly include large patient cohorts and long follow-up periods.…”

“…1A). Positive expression of p21 was defined as a nuclear staining reaction in >5% of the tumor cells according to other publications (9). We observed no p21 expression in 8 carcinomas, a nuclear expression in <5% of the tumor cells in 77 carcinomas and a nuclear expression in >5% in 31 colorectal carcinomas.…”

Hierarchical cluster analysis of myoepithelial/basal cell markers in adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma

“…In recent years, this statistical tool has been applied to analyze immunohistochemical results on Formalinfixed paraffin-embedded tissues using multiple antibodies, and has demonstrated that tumors clustered into groups that correlated to their site of origin, 23 phenotype, 24,25 biologic potential, 26 and prognosis. [27][28][29] Our goal was to identify a cluster of markers that can be used in combination in a diagnostic immunohistochemical panel for differentiating adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma. In this study, 47 tumors were immunostained with primary antibodies against six proteins, and their expressions were subclassified into three categories (negative, focal, and diffuse expression), generating a dataset comprising of 846 (47 Â 6 Â 3) individual observations.…”

Inhibition of STAT5 induces G1 cell cycle arrest and reduces tumor cell invasion in human colorectal cancer cells

“…In general, the molecular mechanisms that control CRC progression are related to the altered expression of different proto-oncogenes, tumor suppressor genes, cytokines and their receptors, including Ras, Src, p27 kip1 , p16 ink4a , interleukin (IL) and the epidermal growth factor receptor (EGFR). [1][2][3][4][5][6][7] Notably, these abnormalities involve the signal transducers and activators of transcription (STAT) signaling pathway, specifically STAT3 and STAT5 signaling, although very few studies have reported the abnormal expression or activation of STAT proteins in colorectal cancer. 8 Understanding the molecular mechanisms of STATs may further the development of novel therapies targeted in CRC treatment.…”