Influence of MRE11, RAD50 and NIBRIN protein expression on survival in pancreatic carcinoma after curative resection

• Published in: Pathology, research and practice research and practice, 2013-10, Vol.209 (10), p.635-639
• Main Authors: Horst, Klemens, Ganzera, Silke, Kaisers, Wolfgang, Munding, Johanna, Flott-Rahmel, Berenike, Tannapfel, Andrea, Zirngibl, Hubert
• Format: Article
• Language: English
• Subjects: Acid Anhydride Hydrolases; Aged; Biomarkers, Tumor - analysis; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - surgery; Cell Cycle Proteins - analysis; Cell Cycle Proteins - biosynthesis; DNA Repair Enzymes - analysis; DNA Repair Enzymes - biosynthesis; DNA-Binding Proteins - analysis; DNA-Binding Proteins - biosynthesis; Female; Humans; Immunohistochemistry; Male; Middle Aged; MRE11; MRE11 Homologue Protein; NIBRIN; Nuclear Proteins - analysis; Nuclear Proteins - biosynthesis; Pancreatic carcinoma; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - surgery; Prognosis; Proportional Hazards Models; RAD50; Survival; Survival Analysis
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1016/j.prp.2013.07.003

The MRE11/RAD50/NIBRIN complex, a protein complex that repairs DNA double-strand breaks, could serve as an early marker for new lesions in pancreatic cancer. We determined the expression of MRE11, RAD50 and NIBRIN, and their possible prognostic value regarding survival. Forty-one patients with ductal adenocarcinoma of the pancreas were included. All underwent curative surgery. Immunohistochemistry was performed for MRE11, RAD50 and NIBRIN. Subsequent analyses were based on a modified immunoreactive score. Statistical analysis was conducted using the statistics program “R”. The mean follow-up period was 509 days. The mean age of the patients was 67±8 years, male=56%, female=44%. Eighty-seven percent underwent a Kausch-Whipple procedure, whereas a left side resection was performed in 22% of patients. Positive lymph nodes were found in 80% of cases, and patients were staged UICC IIa (12%), IIb (56%) and IV (29%). Overall significant results were found for MRE11 (p=0.02) and NIBRIN (p=0.01) expression and postoperative survival. We found a significant relation between the expression of MRE11, NIBRIN and the postoperative survival of patients with ductal adenocarcinoma. The link between the expression of the MRN complex, ATM and pancreatic cancer can be used to develop new treatment options for pancreatic carcinoma.