262 Chapter 11 without. Almost all articles (n = 10/14) state that RAS pathway mutated tumors are not likely to have PM and were not more common in patients with PM compared to without PM. PIK3CA Outcomes The potential association of PIK3CA mutations with PM was analyzed in seven studies. In five studies, the PIK3CA mutations were not significantly associated with PM 28, 33, 35, 37, 44. Christensen et al. even found that PIK3CA mutations were associated with the absence of PM and a decreased hazard of developing PM (HR = 0.31; 95%CI = 0.11–0.86, p = 0.024) in mCRC patients who had received chemo- or immunotherapy treatments 44. Two studies did not report any outcomes, although PIK3CA mutations were investigated 29, 39. TP53 Outcomes TP53 mutations were analyzed in four studies. Two studies showed a significant association between PM and TP53 mutations. Lee et al. detected more TP53 mutations in patients with small obstructive CRC with PM compared to large non-obstructive tumors without PM 30. Sjo et al. performed a multivariate analysis in stage IV CRC patients and showed that PM was significantly associated with TP53 mutations 36. Lan et al. stated that stage IV CRC patients with PM had a higher frequency of TP53 mutations, although the authors did not perform statistical analysis on this association 29. Sayagués et al. did not find a significant association between TP53 mutational status and PM in Caucasian patients diagnosed with CRC 34. Other DNA Outcomes AR, ASXL1, ARID1A, Kif18A, NEK2, MACC1, PAX5, PKHD1, REG1A, RET, Tip60, and UBR5 were mentioned as possible mutated genes associated with PM by several authors 20, 29-32, 38, 41, 50 but were, except for ARID1A, all investigated in only one study. NGS was performed by Yang et al. to detect RET mutations in mCRC without neoadjuvant treatment 50. The presence of RET mutations was significantly associated with PM compared to WT tumors. Tip60 regulation analysis was performed with RT-PCR in patients undergoing surgery for CRC by Sakuraba et al. 32. The authors found that a downregulation of Tip60 was significantly associated with PM. To conclude, all previous mentioned genes showed a significant association with PM, but all were studied by a single study only. RNA Outcomes Nagahara et al. report that Kif18A overexpression, measured by RT-PCR, in CRC patients without neoadjuvant treatment significantly correlates with PM 31. The expression profile of NEK2 was analyzed by Takahashi et al. in patients with CRC who underwent surgical treatment 38, demonstrating that the high NEK2 expression group had significantly greater peritoneal dissemination compared to the low expression group. MACC1 expression was found to be significantly associated with PM by Shirahata et al. 42. The expression of REG1A was explored in non-pretreated CRC patients by Astrosini et al. and showed a positive e correlation with the formation of PM 20. In addition, Heublein et al. analyzed MicroRNAs (miRNAs) expression
RkJQdWJsaXNoZXIy MTk4NDMw