Oh N, et al. Ann Surg Treat Res. 2023 May;104(5):269-273. https://doi.org/10.4174/astr.2023.104.5.269

Mucinous adenocarcinoma (MAC) is a histological subtype of colorectal cancer. The oncologic behavior of MAC differs from nonmucinous adenocarcinoma (non-MAC). Our aim in this study was to characterize patients with colorectal MAC through evaluation of a large, institutional-based cohort with long-term follow-up. A total of 6475 patients with stages I to III colorectal cancer who underwent radical surgery were enrolled from January 2000 to December 2010. Prognostic comparison between MAC (n = 274, 4.2%) and non-MAC was performed. The median follow-up period was 48.0 months. Patients with MAC were younger than those without MAC (P = 0.012) and had larger tumor size (P < 0.001), higher preoperative carcinoembryonic antigen (P < 0.001), higher pathologic T stage (P < 0.001), more right-sided colon cancer (49.3%, P < 0.001), and more frequent high-frequency microsatellite instability (10.2%, P < 0.001). Five-year disease-free survival (DFS) was 76.5% in the MAC group and 83.2% in the non-MAC group (P = 0.008), and 5-year overall survival was 81.4% versus 87.4%, respectively (P = 0.005). Mucinous histology (MAC vs non-MAC) in the entire cohort was not an independent prognostic factor of DFS but had a statistical tendency (P = 0.071). In subgroup analysis of colon cancer without rectal cancer, mucinous histology was an independent prognostic factor (P = 0.026). MAC was found at more advanced stage, located mainly at the right side and was an independent factor of survival in colon cancer. Because of the unique biological behavior of MAC, patients with MAC require special consideration during follow-up.

Purpose: Tumors continuously evolve to maintain growth; secondary mutations facilitate this process, resulting in high tumor heterogeneity. In this study, we compared mutations in paired primary and metastatic colorectal cancer tumor samples to determine whether tumor heterogeneity can predict tumor metastasis. Experimental Design: Somatic variations in 46 pairs of matched primary-liver metastatic tumors and 42 primary tumors without metastasis were analyzed by whole-exome sequencing. Tumor clonality was estimated from single-nucleotide and copy-number variations. The correlation between clinical parameters of patients and clonal heterogeneity in liver metastasis was evaluated. Results: Tumor heterogeneity across colorectal cancer samples was highly variable; however, a high degree of tumor heterogeneity was associated with a worse disease-free survival. Highly heterogeneous primary colorectal cancer was correlated with a higher rate of liver metastasis. Recurrent somatic mutations in APC, TP53, and KRAS were frequently detected in highly heterogeneous colorectal cancer. The variant allele frequency of these mutations was high, while somatic mutations in other genes such as PIK3CA and NOTCH1 were low. The number and distribution of primary colorectal cancer subclones were preserved in metastatic tumors. Conclusions: Heterogeneity of primary colorectal cancer tumors can predict the potential for liver metastasis and thus, clinical outcome of patients. Clin Cancer Res; 23(23); 7209–16. ©2017 AACR.

The prognostic role of surgical resection of primary tumors is not well established in patients with asymptomatic unresectable stage IV colorectal cancer. The aims of this study were to reveal the prognostic role of surgical resection of primary tumors and to define prognostic factors affecting long-term oncological outcomes in patients with asymptomatic unresectable synchronous metastases. This study was a retrospective analysis of prospectively collected data. Between 2000 and 2008, a total of 416 patients with asymptomatic unresectable stage IV colorectal cancer were analyzed with propensity score matching. Prematching baseline characteristics were compared by bivariate analysis, and 113 pairs were selected after 1:1 matching with propensity scores estimated from logistic regression. The primary end point was overall survival. Among 416 patients, 218 (52.4%) underwent palliative resection of the primary tumor. Before propensity score matching, palliative resection resulted in a better survival rate than nonresection in univariate analysis (p < 0.001), but not in multivariate analysis (p = 0.08). After matching, the 5-year overall survival rate was significantly lower for patients with peritoneal metastasis and clinical M1b stage tumors in univariate analysis (p = 0.004 and p = 0.02). However, neither peritoneal metastasis nor clinical M1b stage showed any prognostic significance in multivariate analysis. The overall 5-year survival rate of the postmatching group was 4.9% and 3.5% in the palliative resection and nonresection groups. Consequently, palliative resection was not associated with a significant increase in survival compared with nonresection (p = 0.27). A subgroup analysis performed according to the site of metastasis also did not show any significant survival benefit of palliative resection after matching. Selection bias and potential confounders were limitations of this study. Resection of the primary tumor in patients with asymptomatic unresectable stage IV colorectal cancer was not associated with an improvement in overall survival after propensity score matching.