Abstract
BackgroundColorectal cancer (CRC) remains a serious health concern worldwide. Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRC patients subjected to tumor resection with curative intent, develop disease relapse. Moreover, the therapeutic strategy adopted after surgery is not consensual for these patients. This supports the imperative need to find new prognostic and predictive biomarkers for stage II CRC.MethodsFor this purpose, we used a one-hospital series of 227 stage II CRC patient samples to assess the biomarker potential of the immunohistochemical expression of MUC2 mucin and CDX2 and SOX2 transcription factors. The Kaplan-Meier method was used to generate disease-free survival curves that were compared using the log-rank test, in order to determine prognosis of cases with different expression of these proteins, different mismatch repair (MMR) status and administration or not of adjuvant chemotherapy.ResultsIn this stage II CRC series, none of the studied biomarkers showed prognostic value for patient outcome. However low expression of MUC2, in cases with high expression of CDX2, absence of SOX2 or MMR-proficiency, conferred a significantly worst prognosis. Moreover, cases with low expression of MUC2 showed a significantly clear benefit from treatment with adjuvant chemotherapy.ConclusionIn conclusion, we observe that patients with stage II CRC with low expression of MUC2 in the tumor respond better when treated with adjuvant chemotherapy. This observation supports that MUC2 is involved in resistance to fluorouracil-based adjuvant chemotherapy and might be a promising future predictive biomarker in stage II CRC patients.
Highlights
Colorectal cancer (CRC) remains a serious health concern worldwide
The decision of giving adjuvant treatment based on the administration of fluoropyrimidine to stage II CRC patients is recommended to high risk patients with one or more risk factors: primary tumors diagnosed in T4; poorly differentiated grade, except if associated with mismatch repair (MMR) deficiency; presence of lymphovascular and/or perineural invasion; perforation and/or obstruction; close, undetermined or positive resection margins or less than 12 lymph nodes in the surgical resection specimen [8]
MMR deficiency was evaluated by analysing the expression of the MMR proteins - MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6) and PMS1 homolog 2 (PMS2) – by IHC
Summary
Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRC patients subjected to tumor resection with curative intent, develop disease relapse. Despite that disease-free survival (DFS) among patients with stage III CRC increases significantly with adjuvant chemotherapy regimens, the same is not observed in earlier stages of Ribeirinho-Soares et al BMC Cancer (2021) 21:359. The decision of giving adjuvant treatment based on the administration of fluoropyrimidine to stage II CRC patients is recommended to high risk patients with one or more risk factors: primary tumors diagnosed in T4; poorly differentiated grade, except if associated with mismatch repair (MMR) deficiency; presence of lymphovascular and/or perineural invasion; perforation and/or obstruction; close, undetermined or positive resection margins or less than 12 lymph nodes in the surgical resection specimen [8]. Patients with very high risk - microsatellite stable (MSS) and T4 or more than one corroborated risk factor - may be considered for the addition of oxaliplatin to fluoropyrimidine, whereas for patients with low-risk only follow-up is recommended (Labianca et al, 2013 and respective ESMO Guidelines Committee eUpdate, 2019) [9]
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