The following is a summary of “Molecular Classification of Appendiceal Adenocarcinoma,” published in the March 2023 issue of Oncology by Foote, et al.
For a study, researchers aimed to identify molecular subtypes of appendiceal adenocarcinomas (AC) associated with patient survival, metastatic burden, and chemotherapy response.
They performed a comprehensive molecular analysis on patients with AC to define molecular subtypes and assessed the associations between molecular subtypes and overall survival, intraoperative peritoneal cancer index, and first-line chemotherapy response.
Distinct molecular lineages of mucinous appendiceal adenocarcinoma (MAAP) were defined based on co-occurring mutations in GNAS, RAS, and TP53. They found that patients with RAS-mutant (mut) predominant subtype metastatic MAAP had significantly improved overall survival compared with patients with GNAS-mut and TP53-mut predominant subtypes. Patients with TP53-mut predominant subtypes had highly aneuploid tumors, and increased tumor aneuploidy was associated with poor prognosis. They also found that RAS-mut predominant metastases exhibited reduced peritoneal tumor bulk and stromal invasion compared with GNAS-mut (P = .05) or TP53-mut (P = .004) predominant tumors, respectively. The subtype of TP53-mutant tumors was found to have high levels of aneuploidy, which was independently linked to a poor prognosis (P = .001), and this association was consistent across all patients with metastatic appendiceal cancer. On the other hand, metastatic tumors with RAS mutations had a smaller volume of peritoneal tumors (P = .04) and less stromal invasion (P < .001) compared to those with GNAS or TP53 mutations. Patients with RAS-mutant tumors had a higher response rate (50%) to first-line chemotherapy than those with GNAS-mutant tumors (6%, P = .03).
The findings suggested that AC molecular patterns identified distinct molecular subtypes that exhibit conserved clinical behavior irrespective of histopathology. The researchers identified a clinically indolent RAS-mut/GNAS-wt/TP53-wt subtype, a chemotherapy-resistant GNAS-mut predominant subtype, and an aggressive, highly aneuploid TP53-mut predominant subtype. The findings could guide clinical decision-making and inform treatment strategies for patients with AC.