Daniel B Azambuja1, Natalia M Leguisamo2, Helena C Gloria3, Antonio Nocchi Kalil4, Ernani Rhoden5, Jenifer Saffi6. 1. Department of Colorectal Surgery, Santa Casa de Misericórdia de Porto Alegre (ISCMPA), Porto Alegre, Rio Grande do Sul, 90050-170, Brazil; Laboratory of Genetic Toxicology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, 90050-17, Brazil. Electronic address: dazambuja@uol.com.br. 2. Laboratory of Genetic Toxicology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, 90050-17, Brazil; Molecular and Celular Cardiology Laboratory, Instituto de Cardiologia/Fundação Universitária de Cardiologia do Rio Grande do Sul (IC/FUC), Porto Alegre, Rio Grande do Sul, 90040-371, Brazil. Electronic address: nmleguisamo@gmail.com. 3. Laboratory of Genetic Toxicology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, 90050-17, Brazil. Electronic address: helenadecastroegloria@gmail.com. 4. Department of Colorectal Surgery, Santa Casa de Misericórdia de Porto Alegre (ISCMPA), Porto Alegre, Rio Grande do Sul, 90050-170, Brazil. Electronic address: ankalil@terra.com.br. 5. Department of Surgery, Santa Casa de Misericórdia de Porto Alegre (ISCMPA), Porto Alegre, Rio Grande do Sul, 90050-170, Brazil. Electronic address: ernanirhoden@ufcspa.edu.br. 6. Laboratory of Genetic Toxicology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, 90050-17, Brazil. Electronic address: jenifers@ufcspa.edu.br.
Abstract
OBJECTIVE: to evaluate the prognostic value of base excision repair proteins in sporadic colorectal cancer. METHODS: Pre-treatment tumor samples from 72 patients with sporadic colorectal adenocarcinoma were assessed for APC, MPG, Polβ, XRCC1 and Fen1 expression by immunohistochemistry. The associations of molecular data were analyzed in relation to clinical features and TNM staging as a prognosis predictor and disease-free survival. RESULTS: Higher levels of MPG, Polβ and XRCC1, but not Fen1, were associated with unfavorable pathological outcomes, such as poor cellular differentiation, advanced TNM stages, presence of lymphatic and perineural invasions and metastatic lymph nodes. MPG and Polβ overexpression were associated with right-sided CRC. However, only MPG high expression is associated with shorter disease-free survival in CRC patients. CONCLUSIONS: Our results suggest that increased expression of MPG, Polβ and XRCC1 are more likely to evolve to poor pathological outcomes, but only the elevated expression of MPG protein predicts recurrence. The BER proteins appear to be suitable candidates to refine the TNM current staging of colorectal cancer.
OBJECTIVE: to evaluate the prognostic value of base excision repair proteins in sporadic colorectal cancer. METHODS: Pre-treatment tumor samples from 72 patients with sporadic colorectal adenocarcinoma were assessed for APC, MPG, Polβ, XRCC1 and Fen1 expression by immunohistochemistry. The associations of molecular data were analyzed in relation to clinical features and TNM staging as a prognosis predictor and disease-free survival. RESULTS: Higher levels of MPG, Polβ and XRCC1, but not Fen1, were associated with unfavorable pathological outcomes, such as poor cellular differentiation, advanced TNM stages, presence of lymphatic and perineural invasions and metastatic lymph nodes. MPG and Polβ overexpression were associated with right-sided CRC. However, only MPG high expression is associated with shorter disease-free survival in CRC patients. CONCLUSIONS: Our results suggest that increased expression of MPG, Polβ and XRCC1 are more likely to evolve to poor pathological outcomes, but only the elevated expression of MPG protein predicts recurrence. The BER proteins appear to be suitable candidates to refine the TNM current staging of colorectal cancer.