AIM: The enzyme Cytochrome P450 2W1 (CYP2W1) is found in fetal colon tissue and is also detected in colorectal cancer but not in non-transformed tissue. In a pilot study, we reported that the immunohistochemically-detected expression of CYP2W1 might be of prognostic value since high expression of CYP2W1 was indicative of a worse prognosis. The aim of this study was to validate the pilot study's results using a larger, independent group of patients with colon cancer. MATERIALS AND METHODS: Immunohistochemical detection of CYP2W1 in 235 malignant colon tumors of stage II and III, was carried out using a polyclonal antibody. Grading of staining was carried out by two independent readers. The highest grade that involved more than 5% of the tumor area on each slide was used for the classification of CYP2W1 expression. RESULTS: CYP2W1 was expressed at high levels in 30% of the tumors. In the entire colon cancer group it was an independent prognostic factor in multivariate analysis (p=0.04), where high expression (grade 3) correlated with worse outcome. CYP2W1 expression was an independent prognostic factor in the subgroup of patients with colon cancer stage III (p=0.003), but not for those with stage II. In 107 cases, two slices from different areas of the same tumor were available, and no significant difference in CYP2W1 expression between the slices was observed (r=0.53, p<0.001). CONCLUSION: The results of the current study were in agreement with those of the previous pilot study and show that higher expression of CYP2W1 seems to be of prognostic value in colon cancer. Furthermore, we found equal expression in slices from two different areas of the same tumor. Since the CYP2W1 enzyme has been shown to catalytically activate compounds to cytotoxic products, the enzyme might be used as a novel drug target for the treatment of colon cancer.
AIM: The enzyme Cytochrome P450 2W1 (CYP2W1) is found in fetal colon tissue and is also detected in colorectal cancer but not in non-transformed tissue. In a pilot study, we reported that the immunohistochemically-detected expression of CYP2W1 might be of prognostic value since high expression of CYP2W1 was indicative of a worse prognosis. The aim of this study was to validate the pilot study's results using a larger, independent group of patients with colon cancer. MATERIALS AND METHODS: Immunohistochemical detection of CYP2W1 in 235 malignant colon tumors of stage II and III, was carried out using a polyclonal antibody. Grading of staining was carried out by two independent readers. The highest grade that involved more than 5% of the tumor area on each slide was used for the classification of CYP2W1 expression. RESULTS:CYP2W1 was expressed at high levels in 30% of the tumors. In the entire colon cancer group it was an independent prognostic factor in multivariate analysis (p=0.04), where high expression (grade 3) correlated with worse outcome. CYP2W1 expression was an independent prognostic factor in the subgroup of patients with colon cancer stage III (p=0.003), but not for those with stage II. In 107 cases, two slices from different areas of the same tumor were available, and no significant difference in CYP2W1 expression between the slices was observed (r=0.53, p<0.001). CONCLUSION: The results of the current study were in agreement with those of the previous pilot study and show that higher expression of CYP2W1 seems to be of prognostic value in colon cancer. Furthermore, we found equal expression in slices from two different areas of the same tumor. Since the CYP2W1 enzyme has been shown to catalytically activate compounds to cytotoxic products, the enzyme might be used as a novel drug target for the treatment of colon cancer.
Authors: Jolantha Beyerle; Andreana N Holowatyj; Mariam Haffa; Eva Frei; Biljana Gigic; Petra Schrotz-King; Juergen Boehm; Nina Habermann; Marie Stiborova; Dominique Scherer; Torsten Kölsch; Stephanie Skender; Nikolaus Becker; Esther Herpel; Martin Schneider; Alexis Ulrich; Peter Schirmacher; Jenny Chang-Claude; Hermann Brenner; Michael Hoffmeister; Ulrike Haug; Robert W Owen; Cornelia M Ulrich Journal: Cancer Epidemiol Biomarkers Prev Date: 2019-11-18 Impact factor: 4.254
Authors: Paola Nolé; Britt Duijndam; Adam Stenman; C Christofer Juhlin; Mikael Kozyra; Catharina Larsson; Magnus Ingelman-Sundberg; Inger Johansson Journal: PLoS One Date: 2016-09-06 Impact factor: 3.240
Authors: Silvia Yumi Bando; Priscila Iamashita; Beatriz E Guth; Luis F Dos Santos; André Fujita; Cecilia M Abe; Leandro R Ferreira; Carlos Alberto Moreira-Filho Journal: PLoS One Date: 2017-12-18 Impact factor: 3.240
Authors: Martin J Ronis; Kelly E Mercer; Kartik Shankar; Casey Pulliam; Kim Pedersen; Magnus Ingelman-Sundberg; Simonetta Friso; Derrick Samuelson; Luis Del Valle; Chris Taylor; David A Welsh Journal: Chem Biol Interact Date: 2020-05-14 Impact factor: 5.192