PIK3CA Mutations in Early-Onset Appendiceal Adenocarcinoma.
Princy Gupta1, Rushabh Gujarathi2, Lu Qiao1
1Department of Surgery, Yale School of Medicine, New Haven, CT.
JCO Precision Oncology
|February 19, 2026
Summary
Early-onset appendiceal cancer (EOAC) shows more PIK3CA mutations than late-onset disease. PIK3CA mutations are linked to worse overall survival in appendiceal cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Appendiceal cancer (AC) affects patients of all ages, with a significant portion diagnosed before 50.
- Early-onset appendiceal cancer (EOAC) presents unique characteristics, suggesting underlying biological distinctions from late-onset AC (LOAC).
- Molecular underpinnings of EOAC and LOAC disparities remain largely unexplored.
Purpose of the Study:
- To compare the mutational profiles of EOAC and LOAC.
- To investigate the impact of these molecular differences on overall survival (OS).
Main Methods:
- Retrospective analysis of appendiceal adenocarcinoma cases from the Memorial Sloan Kettering-Metastatic Events and Tropisms database.
- Stratification of patients into EOAC (<50 years) and LOAC (≥50 years) groups.
- Validation using the American Association for Cancer Research Genomics Evidence Neoplasia Information Exchange (GENIE) project data; survival analysis via Kaplan-Meier and Cox models.
Main Results:
- EOAC patients demonstrated a higher prevalence of PIK3CA mutations compared to LOAC patients (17.1% vs 7.7%).
- PIK3CA mutations were more frequent in metastatic disease and in adenocarcinoma not otherwise specified (NOS) compared to mucinous tumors.
- PIK3CA mutations were independently associated with significantly worse overall survival (HR, 2.62; P < .01).
Conclusions:
- PIK3CA mutations are more prevalent in early-onset appendiceal cancer and are an independent predictor of poorer survival.
- Appendiceal cancer prognosis may benefit from incorporating PIK3CA mutation status.
- Targeted therapies inhibiting PIK3CA warrant investigation for appendiceal adenocarcinoma treatment.
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