Maliha Khan1, Jonathan M Loree2, Shailesh M Advani3, Jing Ning4, Wen Li4, Allan A L Pereira2, Michael Lam2, Kanwal Raghav2, Van K Morris2, Russell Broaddus5, Dipen Maru5, Michael J Overman2, Scott Kopetz6. 1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. 2. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. 3. Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC. 4. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX. 5. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. 6. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: SKopetz@mdanderson.org.
Abstract
BACKGROUND: The mucinous histologic subtype accounts for 5% to 20% of colorectal cancer (CRC) cases but remains poorly characterized. The present study characterized the baseline characteristics, mutational profile, and clinical outcomes of patients diagnosed with mucinous CRC. MATERIALS AND METHODS: We identified 1877 patients with metastatic CRC with available histologic findings and molecular profiling and summarized the baseline clinical and pathologic characteristics and overall survival (OS) stratified by the histologic type. The data from separate cohorts with consensus molecular subtype (CMS) and CpG island methylator information were also summarized. RESULTS: The mucinous histologic type was found in 277 of the 1877 patients (14.8%) and was associated with an increased prevalence of microsatellite instability (P < .001) and a right-sided primary (P < .001). An increased frequency of CMS1 (microsatellite instability immune) and lower rates of CMS2 (canonical) were identified, with mucinous compared with nonmucinous adenocarcinoma (P < .0001). Mutations in SMAD4 (P < .001), GNAS (P < .001), ERBB2 (P = .02), BRAF (P < .001), and KRAS (P < .001) occurred at greater frequencies in the mucinous CRC cases, and TP53 (P < .001), APC (P < .001), and NRAS mutations (P = .03) were less common. Univariate (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.17-1.63; P < .001) and multivariate analysis (HR, 1.36; 95% CI, 1.12-1.64; P = .002) demonstrated that the mucinous histologic type is associated with worse OS. The features associated with the mucinous histologic subtype were independent predictors for shorter OS, including BRAF (HR, 1.74; 95% CI, 1.35-2.25; P < .001) and KRAS (HR, 1.42; 95% CI, 1.22-1.65; P < .001) mutations, right-sided location (HR, 1.20; 95% CI, 1.04-1.39; P = .01), and synchronous metastases (HR, 2.92; 95% CI, 2.49-3.42; P < .001). CONCLUSION: Compared with nonmucinous adenocarcinoma, the mucinous histologic type is associated with a worse prognosis, even when controlling for known prognostic features. This unique biologic behavior should be considered in the treatment and prognostic assessment of patients with CRC.
BACKGROUND: The mucinous histologic subtype accounts for 5% to 20% of colorectal cancer (CRC) cases but remains poorly characterized. The present study characterized the baseline characteristics, mutational profile, and clinical outcomes of patients diagnosed with mucinous CRC. MATERIALS AND METHODS: We identified 1877 patients with metastatic CRC with available histologic findings and molecular profiling and summarized the baseline clinical and pathologic characteristics and overall survival (OS) stratified by the histologic type. The data from separate cohorts with consensus molecular subtype (CMS) and CpG island methylator information were also summarized. RESULTS: The mucinous histologic type was found in 277 of the 1877 patients (14.8%) and was associated with an increased prevalence of microsatellite instability (P < .001) and a right-sided primary (P < .001). An increased frequency of CMS1 (microsatellite instability immune) and lower rates of CMS2 (canonical) were identified, with mucinous compared with nonmucinous adenocarcinoma (P < .0001). Mutations in SMAD4 (P < .001), GNAS (P < .001), ERBB2 (P = .02), BRAF (P < .001), and KRAS (P < .001) occurred at greater frequencies in the mucinous CRC cases, and TP53 (P < .001), APC (P < .001), and NRAS mutations (P = .03) were less common. Univariate (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.17-1.63; P < .001) and multivariate analysis (HR, 1.36; 95% CI, 1.12-1.64; P = .002) demonstrated that the mucinous histologic type is associated with worse OS. The features associated with the mucinous histologic subtype were independent predictors for shorter OS, including BRAF (HR, 1.74; 95% CI, 1.35-2.25; P < .001) and KRAS (HR, 1.42; 95% CI, 1.22-1.65; P < .001) mutations, right-sided location (HR, 1.20; 95% CI, 1.04-1.39; P = .01), and synchronous metastases (HR, 2.92; 95% CI, 2.49-3.42; P < .001). CONCLUSION: Compared with nonmucinous adenocarcinoma, the mucinous histologic type is associated with a worse prognosis, even when controlling for known prognostic features. This unique biologic behavior should be considered in the treatment and prognostic assessment of patients with CRC.
Authors: Ashok K Dilly; Brendon D Honick; Robin Frederick; Anuleka Elapavaluru; Sachin Velankar; Hima Makala; T Kevin Hitchens; Lesley M Foley; Jianxia Guo; Jan H Beumer; Lora Heather Rigatti; Yong J Lee; David L Bartlett; Haroon A Choudry Journal: Transl Res Date: 2020-10-22 Impact factor: 7.012
Authors: Ronja S Adam; Dennis Poel; Leandro Ferreira Moreno; Joey M A Spronck; Tim R de Back; Arezo Torang; Patricia M Gomez Barila; Sanne Ten Hoorn; Florian Markowetz; Xin Wang; Henk M W Verheul; Tineke E Buffart; Louis Vermeulen Journal: Mol Oncol Date: 2022-04-29 Impact factor: 7.449
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