The Prognostic Role of Mismatch Repair Status and CDX-2 Expression with Inflammatory Markers and Pathological Risk Factors in Stage II and III Colon Cancer: Multicenter Real-Life Data

• Published in: Journal of gastrointestinal cancer Vol. 55; no. 1; pp. 227 - 236
• Main Authors: Aydin, Sabin Goktas, Olmez, Omer Fatih, Selvi, Oguzhan, Geredeli, Caglayan, Ozden, Ferhat, Bilici, Ahmet, Acikgoz, Ozgur, Karci, Ebru, Kutlu, Yasin, Hamdard, Jamshid, Aydin, Ahmet
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2024
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer Research; CDX2 Transcription Factor - analysis; CDX2 Transcription Factor - genetics; CDX2 Transcription Factor - metabolism; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - mortality; Colonic Neoplasms - pathology; DNA Mismatch Repair; Female; Gastroenterology; Humans; Inflammation - metabolism; Inflammation - pathology; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Recurrence, Local - epidemiology; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Oncology; Prognosis; Radiotherapy; Retrospective Studies; Risk Factors; Inflammatory marker; MSI; Colon cancer; CDX-2; Disease-free survival
• ISSN: 1941-6628; 1941-6636
• DOI: 10.1007/s12029-023-00953-0

Objective Colorectal cancer is common worldwide, and adjuvant treatment’s benefit is still controversial. We designed this study to determine the role of MSI and CDX-2 status determined by immunohistochemistry (IHC) combined with the inflammatory markers and pathological parameters in predicting disease recurrence in stage II and III colon cancer. Methods A total of 226 stage II/III colon cancer patients with a median age of 59 years who underwent initial surgery were included in this retrospective study. The pathologic assessment of MSI and CDX-2 was performed twice by immunohistochemistry (IHC) and two different pathologists. No staining/weak staining below 10% of the tumor was accepted as CDX-2 negative, and any MSI clones with weak staining below 10% were accepted as MSI-H. The laboratory parameters were noted at the initial diagnosis. Results One hundred twenty-one and 105 patients were diagnosed with stage III and II colon cancer. 58.0% of patients were male, 46 (20.4%) of tumor tissue were MSS, and 17 (7.5%) were CDX-2 negative. One hundred twenty-nine tumors were localized in the right colon. Disease recurrence was significantly correlated with tumor localization, CDX-2 status, stage at diagnosis, and preoperatively median CRP and CEA levels. DFS rates for MSS patients with CDX-2 negative and positive were 36.7% and 98.1%, respectively [ p  < 0.001]. There was no significant correlation between MSI status and CDX-2 status. MSI status, the presence of adjuvant treatment, and systemic inflammatory markers were not significant prognostic factors for DFS. CDX-2 status [HR:0.08, CI 95% 0.03–0.17, p  < 0.001 HR: 1.7, CI 95% 1.1–3.0, p  = 0.03], disease stage [HR:2.6, CI 95% 1.43–4.74], and preoperatively CEA levels [HR:4.1 CI 95% 2.18–785, p  < 0.001 were independent significant prognostic factors for DFS. Conclusion CDX-2 loss was an independent prognostic factor for DFS and disease recurrence in early-stage colon cancer. MSS patients with CDX-2 loss had significantly worse survival outcomes, and this might be the reason for deciding on adjuvant chemotherapy.