Peritoneal metastases from primary appendiceal and colorectal carcinomas demonstrate distinct molecular identities on comprehensive tumor analysis

Andrew M. Fleming, Benjamin W. Deschner, Forrest W. Williard, Justin A. Drake, Ari Vanderwalde, Joanne Xiu, Bradley G. Somer, Danny Yakoub, Miriam W. Tsao, Evan S. Glazer, Paxton V. Dickson, David Shibata, Philip A. Philip, Jimmy J. Hwang, Anthony F. Shields, John L. Marshall, W. Michael Korn, Heinz Josef Lenz, Jeremiah L. Deneve

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Objectives: Published data comparing peritoneal metastases from appendiceal cancers (pAC) and colorectal cancers (pCRC) remain sparse. We compared pAC and pCRC using comprehensive tumor profiling (CTP). Methods: CTP was performed, including next-generation sequencing and analysis of copy number variation (CNV), microsatellite instability (MSI) and tumor mutational burden (TMB). Results: One hundred thirty-six pAC and 348 pCRC samples underwent CTP. The cohorts' age and gender were similar. pCRC demonstrated increased pathogenic variants (PATHs) in APC (48% vs. 3%, p < 0.01), ARID1A (12% vs. 2%, p < 0.01), BRAF (12% vs. 2%, p < 0.01), FBXW7 (7% vs. 2%, p < 0.01), KRAS (52% vs. 41%, p < 0.05), PIK3CA (15% vs. 2%, p < 0.01), and TP53 (53% vs. 23%, p < 0.01), and decreased PATHs in GNAS (8% vs. 31%, p < 0.01). There was no difference in CNV, fusion rate, or MSI. Median TMB was higher in pCRC (5.8 vs. 5.0 mutations per megabase, p = 0.0007). Rates of TMB-high tumors were similar (pAC 2.1% vs. pCRC 9.0%, p = 0.1957). pCRC had significantly more TMB-high tumors at lower thresholds. Conclusions: Despite a reduced overall TMB, pAC demonstrated mutations distinct from those seen in pCRC. These may serve as discrete biomarkers for future study.

Original languageEnglish (US)
Pages (from-to)815-822
Number of pages8
JournalJournal of Surgical Oncology
Volume127
Issue number5
DOIs
StateAccepted/In press - 2023
Externally publishedYes

Keywords

  • appendiceal neoplasms
  • colorectal neoplasms
  • neoplasm metastasis
  • peritoneal neoplasms
  • peritoneum

ASJC Scopus subject areas

  • Surgery
  • Oncology

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