Pattern‐Based P53 Immunohistochemistry Predicts Recurrence in Colorectal Liver Metastases Without Complete Pathologic Response After Neoadjuvant Chemotherapy

ABSTRACT Background Aberrant p53 expression may have prognostic significance in colorectal cancer; however, its role in patients with colorectal liver metastases (CRLM) who receive neoadjuvant chemotherapy but do not achieve pathological complete response (pCR) remains unclear. Aims We evaluated whether aberrant p53 expression assessed by immunohistochemistry (IHC) predicts recurrence‐free survival (RFS) in patients with CRLM receiving neoadjuvant FOLFOXIRI followed by resection without achieving pCR. Methods and Results A prospective cohort study was conducted on 39 patients with CRLM who met the inclusion criteria. All patients received neoadjuvant chemotherapy with the FOLFOXIRI regimen. Following surgical resection of both primary colorectal tumors and liver metastases, none of the patients achieved pCR. Immunohistochemistry was performed to assess p53 expression in resected liver metastasis specimens using a pattern‐based interpretation model. RFS was analyzed using univariate and multivariate Cox proportional hazards models. Aberrant p53 expression was observed in 20 patients (51.3%). In univariate analysis, aberrant p53 expression (HR = 2.20; 95% CI: 1.02–4.71; p  = 0.043), total tumor size > 6 cm (HR = 5.62; 95% CI: 2.31–13.68; p   4 (HR = 4.41; 95% CI: 1.59–12.26; p  = 0.004), and positive surgical margin (HR = 2.62; 95% CI: 1.16–5.91; p  = 0.021) were significantly associated with recurrence. In multivariate analysis, aberrant p53 expression (HR = 3.78; 95% CI: 1.56–9.15; p  = 0.003) and total tumor size > 6 cm (HR = 5.23; 95% CI: 1.56–17.55; p  = 0.007) remained independent prognostic factors for shorter RFS.cnr270701_RedLinePDF. Conclusion Aberrant p53 expression, as assessed by immunohistochemistry on post‐neoadjuvant chemotherapy specimens, is an independent prognostic factor for early recurrence in patients with CRLM who did not achieve pCR. Together with total tumor size, aberrant p53 expression may serve as a useful marker for risk stratification and personalized postoperative treatment strategies in this high‐risk patient population.