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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

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Abstract

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.

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Data Availability

The data supporting this study’s findings are not openly available. Further enquiries can be directed to the corresponding author.

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Authors and Affiliations

  1. Department of Medical Oncology, Medical Faculty, Istanbul Medipol University, TEM Avrupa Otoyolu Goztepe, Cikisi, No:1, Bagcilar, 34214, Istanbul, Turkey

    Sabin Goktas Aydin, Omer Fatih Olmez, Ahmet Bilici, Ozgur Acikgoz, Ebru Karci, Yasin Kutlu & Jamshid Hamdard

  2. Department of Medical Oncology, Okmeydani Training and Research Hospital, Kaptan Paşa Mahallesi, Darülaceze Cad. No:25, 34384, Okmeydani, Istanbul, Turkey

    Oguzhan Selvi & Caglayan Geredeli

  3. Department of Pathology, Medical Faculty, Istanbul Medipol University, TEM Avrupa Otoyolu Goztepe, Cikisi, No:1, Bagcilar, 34214, Istanbul, Turkey

    Ferhat Ozden

  4. Department of Internal Medicine, Medical Faculty, Istanbul Medipol University, TEM Avrupa Otoyolu Goztepe, Cikisi, No:1, Bagcilar, 34214, Istanbul, Turkey

    Ahmet Aydin

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  1. Sabin Goktas Aydin
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Contributions

S. Goktas Aydin and O.F. Olmez designed the study. S. Goktas Aydin and O. F. Olmez wrote the manuscript. A. Bilici and S. Goktas Aydin conceived the statistical data analysis. Y. Kutlu, J. Hamdard, O. Selvi, C. Geredeli, O. Acikgoz, E. Karci, and A. Aydin contributed substantial input to the conception and acquisition of the work. F. Ozden was responsible for pathologic evaluation. All authors read and gave their stamp of approval for the submission of the final version of the manuscript.

Corresponding author

Correspondence to Sabin Goktas Aydin.

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Ethics Approval

The Local Ethics Committee of Istanbul Medipol University approved this multicenter study in December 2020 with the E-10840098-772.02-65178 decision number. Written informed consent had been obtained from patients.

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The authors declare no competing interests.

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Aydin, S.G., Olmez, O.F., Selvi, O. et al. 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. J Gastrointest Canc 55, 227–236 (2024). https://doi.org/10.1007/s12029-023-00953-0

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