학술논문

Expression of the DNA repair gene MLH1 correlates with survival in patients who have resected pancreatic cancer and have received adjuvant chemoradiation: NRG Oncology RTOG Study 9704
Document Type
article
Source
Cancer. 124(3)
Subject
Rare Diseases
Clinical Research
Pancreatic Cancer
Clinical Trials and Supportive Activities
Digestive Diseases
Cancer
Genetics
Adult
Aged
Aged
80 and over
Chemoradiotherapy
Adjuvant
DNA Damage
Female
Humans
Male
Middle Aged
MutL Protein Homolog 1
Pancreatic Neoplasms
Proportional Hazards Models
Prospective Studies
biomarkers
chemotherapy
adjuvant
clinical trial phase 3
mutL protein homolog 1
pancreatic neoplasms
radiotherapy
tumor
Oncology and Carcinogenesis
Public Health and Health Services
Oncology & Carcinogenesis
Language
Abstract
BACKGROUND:The majority of patients with pancreatic cancer who undergo curative resection experience rapid disease recurrence. In previous small studies, high expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in pancreatic cancers was associated with better outcomes. The objective of this study was to validate the association between MLH1 expression and survival in patients who underwent resection of pancreatic cancer and received adjuvant chemoradiation. METHODS:Samples were obtained from the NRG Oncology Radiation Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials.gov identifier NCT00003216), which compared 2 adjuvant protocols in patients with pancreatic cancer who underwent resection. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded, resected tumor tissues. MLH1 expression was quantified using fluorescence immunohistochemistry and automated quantitative analysis, and expression was dichotomized above and below the median value. RESULTS:Immunohistochemical staining was successfully performed on 117 patients for MLH1 (60 and 57 patients from the 2 arms). The characteristics of the participants who had tissue samples available were similar to those of the trial population as a whole. At the time of analysis, 84% of participants had died, with a median survival of 17 months. Elevated MLH1 expression levels in tumor nuclei were significantly correlated with longer disease-free and overall survival in each arm individually and in both arms combined. Two-year overall survival was 16% in patients who had low MLH1 expression levels and 53% in those who had high MLH1 expression levels (P