Background: CRC patients with PM have a significantly worse median overall survival (OS) when compared to those with liver and lung metastases. We studied MSLN protein expression using immunohistochemistry (IHC) on primary resected CRC (PRC), its correlation with future development of PM and its effect on OS. Our hypothesis is that PRC tumors from patients who later developed PM will have an increased proportion of positive MSLN scores based on IHC. Methods: We performed a retrospective case control study of all localized CRC (Stage I, II, III) patients who underwent curative resection from 2000- 2017 at the University of Oklahoma. The target population consisted of PRC patients who had distant recurrence during surveillance. Control group comprised of patients who never recurred after a minimum of 5 years of surveillance. MSLN score was calculated by the sum of staining percentage and intensity scores on each MSLN stained slide. Kaplan-Meier method was used to estimate OS and differences in survival were estimated using log-rank test. Results: Among 100 patients with recurrent CRC, 19 patients had PM, 51 had solid organ only metastases (SOM) and 66 are in the control group. MSLN staining results by IHC were satisfactory in 87 patients (Table). 91%, 46% and 21% of the patients in PM, SOM, and control groups had a positive MSLN score on PRC respectively. A significant association between MSLN score and future development of PM was observed (p<0.001) based on Fisher’s exact test. Sensitivity of MSLN as a marker for future PM was 93% and specificity was 58%. Patients with a positive MSLN score had a poor OS when compared to those with a negative MSLN score on univariate analysis (95% CI: 4.1-NR (not reached), p <0.001), which lost significance on multi-variable cox proportional analyses. Conclusions: A higher proportion of patients in the PM group had a positive MSLN score on PRC when compared to the SOM and control groups. MSLN was found to be a highly sensitive marker for future PM in CRC. We intend to expand this work by examining an additional cohort to validate these findings.

OS and MSLN score in three groups.