Details

Autor(en) / Beteiligte

• Foote, Michael B
• Walch, Henry
• Chatila, Walid
• Vakiani, Efsevia
• Chandler, Chris
• Steinruecke, Felix
• Nash, Garrett M
• Stadler, Zsofia
• Chung, Sebastian
• Yaeger, Rona
• Braghrioli, Maria Ignez
• Shia, Jinru
• Kemel, Yelena
• Maio, Anna
• Sheehan, Margaret
• Rousseau, Benoit
• Argilés, Guillem
• Berger, Michael
• Solit, David
• Schultz, Nikolaus
• Diaz, Jr, Luis A
• Cercek, Andrea

Titel

Molecular Classification of Appendiceal Adenocarcinoma

Ist Teil von

• Journal of clinical oncology, 2023-03, Vol.41 (8), p.1553-1564

Ort / Verlag

United States: Wolters Kluwer Health

Erscheinungsjahr

2023

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Appendiceal adenocarcinomas (ACs) are rare, histologically diverse malignancies treated as colorectal cancers despite having distinct biology and clinical behavior. To guide clinical decision making, we defined molecular subtypes of AC associated with patient survival, metastatic burden, and chemotherapy response. A comprehensive molecular analysis was performed in patients with AC to define molecular subtypes. Associations between molecular subtype and overall survival, intraoperative peritoneal cancer index, and first-line chemotherapy response were assessed adjusting for histopathologic and clinical variables using multivariable Cox proportional hazards, linear regression, and logistic regression models. We defined distinct molecular lineages of mucinous appendiceal adenocarcinoma (MAAP) from co-occurring mutations in , , and . Of 164 MAAP tumors, 24 were RAS-mutant (mut) predominant ( -mut/ -wild-type [wt]/ -wt) with significantly decreased mutations and chromosomal alterations compared with tumors with mutations (GNAS-mut predominant) or mutations (TP53-mut predominant). No patient with RAS-mut predominant subtype metastatic MAAP died of cancer, and overall survival in this subgroup was significantly improved compared with patients with GNAS-mut ( = .05) and TP53-mut ( = .004) predominant subtypes. TP53-mut predominant subtypes were highly aneuploid; increased tumor aneuploidy was independently ( = .001) associated with poor prognosis. The findings retained significance in patients with any metastatic AC. RAS-mut predominant metastases exhibited reduced peritoneal tumor bulk ( = .04) and stromal invasion ( < .001) compared with GNAS-mut or TP53-mut predominant tumors, respectively. Patients with RAS-mut predominant MAAP responded more to first-line chemotherapy (50%) compared with patients with GNAS-mut predominant tumors (6%, = .03). AC molecular patterns identify distinct molecular subtypes: 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. Each subtype exhibits conserved clinical behavior irrespective of histopathology.