p53 expression status is associated with cancer-specific survival in stage III and high-risk stage II colorectal cancer patients treated with oxaliplatin-based adjuvant chemotherapy.

BACKGROUND: We attempted to elucidate whether p53 expression or TP53 mutation status was associated with cancer-specific survival in adjuvant FOLFOX-treated patients with stage III or high-risk stage II colorectal cancer (CRC). METHODS: We analysed CRCs (N = 621) for the presence of TP53 alterations and for p53 expression, using targeted resequencing and immunohistochemistry. CRCs were grouped into four subsets according to the p53 expression status, which included p53-no, mild, moderate and strong expression. RESULTS: The distributions of CRCs were 19.85, 11.05, 17.7% and 51.5% in the p53-no, mild, moderate and strong expression groups, respectively. Cases in the p53-mild to moderate expression group were associated with a more frequent proximal location, undifferentiated histology, lower N category, extraglandular mucin production, microsatellite instability, CIMP-P1, CK7 expression and decreased CDX2 expression compared with those of cases of the p53-no expression and p53-strong expression groups. According to survival analysis, the p53-mild expression group showed a poor 5-year relapse-free survival (hazard ratio (HR): 2.71, 95% confidence interval (CI) = 1.60-4.60, P < 0.001) and poor 5-year cancer-specific survival (HR: 2.90, 95% CI = 1.28-6.57, P = 0.011). CONCLUSIONS: p53-mild expression status was found to be an independent prognostic marker in adjuvant FOLFOX-treated patients with stage III and high-risk stage II CRC.

Associations and prognostic implications of Eastern Cooperative Oncology Group performance status and tumoral LINE-1 methylation status in stage III colon cancer patients.

BACKGROUND: Low methylation status of LINE-1 in tumors is associated with poor survival in patients with colon cancer. Eastern Cooperative Oncology Group performance status (ECOG-PS) is a method to assess the functional status of a patient. We retrospectively evaluated the relationship between ECOG-PS and LINE-1 methylation in colorectal cancers (CRCs) and their prognostic impact in CRC or colon cancer patients receiving adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX). RESULTS: LINE-1 methylation and microsatellite instability were analyzed in stage III or high-risk stage II CRCs (n = 336). LINE-1 methylation levels were correlated with clinicopathological features, including PS and recurrence-free survival (RFS). The association between the tumoral LINE-1 methylation level and PS was observed (OR = 2.56, P < 0.001). Differences in LINE-1 methylation levels in cancer tissue between the PS 0 and 1 groups were significant in patients older than 60 years (P = 0.001), the overweight body mass index group (P = 0.005), and the stage III disease group (P = 0.008). Prognostic significances of LINE-1 methylation status or combined PS and LINE-1 methylation statuses were identified in stage III colon cancers, not in stage III and high-risk stage II CRCs. Low LINE-1 methylation status was closely associated with a shorter RFS time. The difference between PS(0)/LINE-1(high) and PS(≥1)/LINE-1(low) was significant, which suggests that colon cancer patients with concurrent PS(≥1)/LINE-1 (low) have a higher recurrence rate. CONCLUSIONS: PS was associated with LINE-1 methylation in CRC tissue. LINE-1 methylation was associated with RFS in stage III colon cancer patients who were treated with adjuvant FOLFOX chemotherapy. Combined PS and LINE-1 methylation status might serve as a useful predictor of cancer recurrence.