Mucinous adenocarcinoma of the colon (MAC) is a distinct histological subtype of colorectal cancer (CRC), defined by the presence of ≥50% extracellular mucin. This CRC subtype exhibits unique clinical and molecular characteristics, including more frequent localization in the right colon, higher prevalence among younger patients, and associations with microsatellite instability-high (MSI-H) and BRAF gene mutations. Evidence suggests that MAC demonstrates a poorer response to conventional therapies; however, the independent prognostic value of the mucinous component remains unclear.

This narrative review aims to evaluate the prognostic significance of the mucinous component in CRC. Twenty relevant studies published between 2018 and 2025 were analyzed. Results indicate that MAC is more often detected at advanced stages and shows a weaker response to fluorouracil-based regimens and neoadjuvant chemoradiotherapy in rectal tumors. Nonetheless, several studies reported no significant difference in overall survival between mucinous and non-mucinous carcinomas. Additionally, immune-related factors such as tumor-infiltrating lymphocytes (TILs) and desmoplasia are gaining importance and may have greater prognostic value than mucinous differentiation itself.

MAC also frequently exhibits marked molecular heterogeneity, complicating prognosis and treatment decisions. Consequently, careful patient monitoring and timely molecular profiling are essential for optimizing therapy. Novel artificial intelligence–based models that integrate histological images, molecular biomarkers, and clinical data show promise for personalizing treatment in MAC.

In conclusion, although MAC is currently treated according to standard CRC guidelines, its distinct features underscore the need for individualized therapeutic approaches and further clinical research.

 

mucinous adenocarcinoma, colorectal cancer, prognosis, MSI-H, treatment response

 

1. Reynolds IS, O’Connell E, Fichtner M, McNamara DA, Kay EW, Prehn JHM, et al. Mucinous adenocarcinoma of the colon and rectum: a genomic analysis. J Surg Oncol. 2019;120(8):1427–35. doi: 10.1002/jso.25764.
2. Eunus MF, Saleh FM, Karim SN, Tanzim MA, Hossain MI. Clinicopathological characteristics of mucinous and non-mucinous adenocarcinoma of the colon and rectum. Mymensingh Med J. 2023;32(2):480–6.
3. Fadel MG, Malietzis G, Constantinides V, Pellino G, Tekkis P, Kontovounisios C. Clinicopathological factors and survival outcomes of signet-ring cell and mucinous carcinoma versus adenocarcinoma of the colon and rectum: a systematic review and meta-analysis. Discov Oncol. 2021;12(1):5. doi: 10.1007/s12672-021-00398-6.
4. Kim S, Huh JW, Lee WY, Yun SH, Kim HC, Cho YB, et al. Prognostic impact of mucinous adenocarcinoma in stage II and III colon cancer. Dis Colon Rectum. 2023;66(11):1473–80. doi: 10.1097/DCR.0000000000002733.
5. Zhu L, Ling C, Xu T, Zhang J, Zhang Y, Liu Y, et al. Clinicopathological features and survival of signet-ring cell carcinoma and mucinous adenocarcinoma of right colon, left colon, and rectum. Pathol Oncol Res. 2021;27:1609800. doi: 10.3389/pore.2021.1609800.
6. Reynolds IS, O’Connell E, Fichtner M, Blümel A, Mason SE, Kinross J, et al. An insight into the driver mutations and molecular mechanisms underlying mucinous adenocarcinoma of the rectum. Dis Colon Rectum. 2021;64(6):677–88. doi: 10.1097/DCR.0000000000001825.
7. Kepil N, Batur S, Goksel S. Immunohistochemical and genetic features of mucinous and signet-ring cell carcinomas of the stomach, colon and rectum: a comparative study. Int J Clin Exp Pathol. 2019;12(9):3483–91.
8. Huang L, Luo S, Lai S, Liu Z, Hu H, Chen M, et al. Survival after curative resection for stage I colorectal mucinous adenocarcinoma. BMC Gastroenterol. 2022;22(1):192. doi: 10.1186/s12876-022-02276-z.
9. Dai D, Zhou B, Zhong Y, Jin H, Wang X. Survival of patients with resected primary colorectal mucinous adenocarcinoma: A competing risk nomogram analysis. Oncol Lett. 2019;18(6):6594–604. doi: 10.3892/ol.2019.11024.
10. McCawley N, Clancy C, O’Neill BD, Deasy J, McNamara DA, Burke JP. Mucinous rectal adenocarcinoma is associated with a poor response to neoadjuvant chemoradiotherapy: a systematic review and meta-analysis. Dis Colon Rectum. 2016;59(12):1200–8. doi: 10.1097/DCR.0000000000000635.
11. Moretto R, Morano F, Ongaro E, Rossini D, Pietrantonio F, Casagrande M, et al. Lack of benefit from anti-EGFR treatment in RAS and BRAF wild-type metastatic colorectal cancer with mucinous histology or mucinous component. Clin Colorectal Cancer. 2019;18(2):116–24. doi: 10.1016/j.clcc.2019.02.007.
12. Wu M, Huang M, He C, Chen C, Li H, Wang J, et al. Risk of second primary malignancies based on the histological subtypes of colorectal cancer. Front Oncol. 2021;11:650937. doi: 10.3389/fonc.2021.650937.
13. Yang L, Dong D, Fang M, Zhu Y, Zang Y, Liu Z, et al. Can CT-based radiomics signature predict KRAS/NRAS/BRAF mutations in colorectal cancer? EurRadiol. 2018;28(5):2058–67. doi: 10.1007/s00330-017-5146-8.
14. Shaish H, Aukerman A, Vanguri R, Spinelli A, Armenta P, Jambawalikar S, et al. Radiomics of MRI for pretreatment prediction of pathologic complete response, tumor regression grade, and neoadjuvant rectal score in patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation: an international multicenter study. Eur Radiol. 2020;30(11):6263–73. doi: 10.1007/s00330-020-06968-6.
15. Li Y, Eresen A, Shangguan J, Yang J, Benson AB 3rd, Yaghmai V, et al. Preoperative prediction of perineural invasion and KRAS mutation in colon cancer using machine learning. J Cancer Res Clin Oncol. 2020;146(12):3165–74. doi: 10.1007/s00432-020-03354-z.
16. Caruso D, Polici M, Zerunian M, Monterubbiano A, Tarallo M, Pilozzi E, et al. CT-based radiogenomic analysis to predict high-risk colon cancer (ATTRACT): a multicentric trial. Eur Radiol. 2025 Jun 5. doi: 10.1007/s00330-025-11728-5. Online ahead of print.
17. Mei WJ, Mi M, Qian J, Xiao N, Yuan Y, Ding PR. Clinicopathological characteristics of high microsatellite instability/mismatch repair-deficient colorectal cancer: a narrative review. Front Immunol. 2022;13:1019582. doi:10.3389/fimmu.2022.1019582.
18. Golia Pernicka JS, Gagniere J, Chakraborty J, Yamashita R, Nardo L, Creasy JM, et al. Radiomic-based prediction of microsatellite instability in colorectal cancer at initial computed tomography evaluation. Abdom Radiol (NY). 2019;44(11):3755–63. doi: 10.1007/s00261-019-02117-w.
19. Abbaspour E, Karimzadhagh S, Monsef A, Joukar F, Mansour Ghanaei F, Hassanipour S. Application of radiomics for preoperative prediction of lymph node metastasis in colorectal cancer: a systematic review and meta-analysis. Int J Surg. 2024;110(6):3795–813. doi: 10.1097/JS9.0000000000001239.