Sidedness Matters: Surrogate Biomarkers Prognosticate Colorectal Cancer upon Anatomic Location

• Published in: The oncologist (Dayton, Ohio) Ohio), 2019-08, Vol.24 (8), p.e696-e701
• Main Authors: Ben‐Aharon, Irit, Goshen‐Lago, Tal, Sternschuss, Michal, Morgenstern, Sara, Geva, Ravit, Beny, Alexander, Dror, Ygael, Steiner, Mariana, Hubert, Ayala, Idelevich, Efraim, Shulman, Katerina, Mishaeli, Moshe, Man, Sophia, Liebermann, Nicky, Soussan‐Gutman, Lior, Brenner, Baruch
• Format: Article
• Language: English
• Subjects: CDX2; Gastrointestinal Cancer; Oncotype Recurrence Score assay; Prognostic biomarkers; Stage II colorectal cancer; Tumor location
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2018-0351

Background Anatomic location of primary tumors across the colon correlate with survival in the metastatic setting, whereas left‐sided tumors may exhibit superior survival compared with right‐sided tumors. The Oncotype Recurrence Score (RS) assay is a clinically validated predictor of recurrence risk in patients with stage II colorectal cancer (CRC). Previous studies had indicated that without adjuvant chemotherapy, CDX2‐negative stage II CRC tumors are associated with a lower rate of disease‐free survival than CDX2‐positive stage II CRC tumors. We aimed to evaluate whether these two validated prognostic biomarkers may correlate with primary tumor location, and whether tumor location may reflect differential prognosis in stage II CRC. Materials and Methods We retrospectively analyzed patients with T3 mismatch repair‐proficient (MMR‐P) stage II CRC for whom RS assay was performed. Pathological report was reviewed for exact primary tumor location and CDX2 immunostaining. RS and CDX2 expression were correlated with primary tumor location. Results The analysis included 1,147 patients with MMR‐P stage II CRC (median age 69 years [range 29–93]). Tumor distribution across the colon was as follows: 46% (n = 551) were right‐sided and 54% (n = 596) were left‐sided. RS was higher in right‐sided tumors (p = .01). The RS results gradually decreased across the colon (cecum, highest score; sigmoid, lowest score; p = .04). Right‐sided tumors exhibited more CDX2‐negative tumors (p = .07). Conclusion Our study indicates that right‐sided colorectal tumors may display worse prognosis compared with left‐sided tumors in MMR‐P stage II CRC. Primary tumor location may serve as a prognostic factor that should be taken into account for recurrence risk assessment and consideration of adjuvant treatment. Implications for Practice Sidedness matters, even in stage II colorectal cancer (CRC). Using two previously established prognostic tools, the Oncotype DX assay and CDX2 expression, this study found that right‐sided tumors may display worse prognosis compared with left‐sided tumors in mismatch repair‐proficient stage II CRC. Therefore, primary tumor location should be taken into account for recurrence risk assessment and consideration of adjuvant treatment. 摘要 背景。在转移性结直肠癌中，原发性肿瘤的解剖位置与存活率相关，而与右侧肿瘤相比，左侧肿瘤可能表现出更高的存活率。肿瘤基因复发评分 (RS) 测定是经过临床验证的 II 期结直肠癌 (CRC) 患者复发风险的预测因子。既往研究已表明，如果没有辅助化疗，CDX2 阴性的 II 期 CRC 肿瘤与 CDX2 阳性的 II 期 CRC 肿瘤相比具有更低的无病生存率。我们的目的是评估这两种经过验证的预后生物标记物是否与肿瘤的原发部位相关，以及肿瘤部位是否可能反映出