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. 2022 Dec 28;15(1):181. doi: 10.3390/cancers15010181

Figure 1.

Figure 1

Clinical and molecular influence on the aggressiveness of colorectal liver metastasis. (A) Clinical behavior of colorectal cancer is determined by several factors, including demographic data (age, gender, and race), tumor presentation (location and stage), and timing of presentation of metastasis (synchronous or metachronous). Embedded in the cancer cells are the molecular pathways, which follow distinct forms of genomic instability yet with partly overlapping areas. Hypermutated cancers belong to the microsatellite instable (MSI) cancers and in part the CpG-island methylator phenotype (CIMP) cancers. Nonhypermutated cancers follow in large part the chromosomal instability (CIN)–driven pathways, often involving KRAS mutations from an early stage. The propensity to develop metastasis may possibly be modified through the elevated microsatellite alterations at selected tetranucleotide repeat (EMAST) and associated mechanisms, such as regulation of microRNAs or activity and numbers of CD8+ immune cells. Finally, the microenvironment contains numerous factors that may facilitate or propagate metastasis to invade, spread, and settle in new organ sites, particularly the liver and the lungs. (B) Determined by the clinical presentation, the genetic traits, and molecular mechanisms, the prognosis in colorectal liver metastasis is related to resectabilty for long-term survival. “Good” cases amenable for surgery have fewer bad genetic traits, such as less likelihood for BRAF mutations or KRAS mutations and were more likely to have EMAST and MSI-L alone in the current study. Patients with concomitant liver and lung metastases have an “ugly” tumor biology and are more likely to have higher frequencies of both KRAS and BRAF mutations and respond poorly to any line of treatment. The “bad” cases are in between, and the shift from “nonresectable” to “resectable” experiences a positive drift with time and where changing practice in surgical strategy, novel techniques, and use of conversion chemotherapy regimens improve outcomes. Novel biomarkers may aid in understanding aggressiveness of liver metastasis, assist in clinical decision making, and help to find new and more efficient therapies. Reproduced with permission from Soreide et al. Gastroenterology 2016 Apr;150(4):811-4, 2016 © AGA, published by Elsevier.