Pathological risk factors for lymph node metastasis in patients with submucosal invasive colorectal carcinoma

Background: Risk grade assessment determines therapy in patients with submucosal invasive colorectal carcinoma (CRC). However, treatment decisions are often difficult due to a lack of consensus on which risk factors should be considered. We aimed to identify predictive risk factors for lymph node metastasis (LNM) in a large cohort of submucosal invasive CRC patients from China. Patients and methods: Following collection of clinicopathological data and disease-free survival (DFS) rates from 290 patients who underwent radical intestinal resection with regional lymphadenectomy, we immunohistochemically assessed expression of DNA mismatch repair (MMR) proteins and p53. The correlation between clinicopathological parameters, MMR expression, p53 status, and LNM status was determined using chi-squared tests and logistic analysis. Receiver operator characteristic curve analysis was used to compare the predictive values. The DFS curves were plotted using the Kaplan-Meier method. Results: LNM was detected in 15.5% of the cases (45/290 patients). Three pathological characteristics, high tumor differentiation grade, lymphovascular invasion (LVI), and tumor budding, were all positively related to LNM in univariate and multivariate analyses (P<0.05). MMR status did not correlate with either LNM or the pathological characteristics (P>0.05). Overexpression of p53 was associated with tumor budding status (P=0.036). With a negative predicative value of 0.92 and area under the curve of 0.76 (95% CI: 0.68-0.85), the combination of these three factors provided optimal predictive ability. Patients with all three risk factors had poorer DFS (P<0.001). Conclusion: High tumor grade, LVI, and positive tumor budding serve as useful LNM predictors in submucosal invasive CRC.