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

doi:10.1002/jso.27198

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

J Surg Oncol. 2023 Apr;127(5):815-822. doi: 10.1002/jso.27198. Epub 2023 Jan 11.

Authors

Andrew M Fleming¹, Benjamin W Deschner^{1

2}, Forrest W Williard³, Justin A Drake¹, Ari Vanderwalde^{4

5}, Joanne Xiu⁵, Bradley G Somer⁴, Danny Yakoub⁶, Miriam W Tsao^{1

2}, Evan S Glazer^{1

2}, Paxton V Dickson^{1

2}, David Shibata^{1

2}, Philip A Philip⁷, Jimmy J Hwang⁸, Anthony F Shields⁷, John L Marshall⁹, W Michael Korn¹⁰, Heinz-Josef Lenz¹¹, Jeremiah L Deneve^{1

2}

Affiliations

¹ Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
² Division of Surgical Oncology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
³ College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
⁴ West Cancer Center, Germantown, Tennessee, USA.
⁵ Caris Life Sciences, Irving, Texas, USA.
⁶ Department of Surgery, Mayo Clinic Health System, Eau Claire, Wisconsin, USA.
⁷ Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
⁸ Division of Hematology/Oncology, Atrium Health Levine Cancer Institute, Charlotte, North Carolina, USA.
⁹ Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia, USA.
¹⁰ Division of Hematology/Oncology, University of California, San Francisco, California, USA.
¹¹ Keck School of Medicine, Norris Comprehensive Cancer Center, Division of Medical Oncology, University of Southern California, Los Angeles, California, USA.

PMID: 36629137
DOI: 10.1002/jso.27198

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.

Keywords: appendiceal neoplasms; colorectal neoplasms; neoplasm metastasis; peritoneal neoplasms; peritoneum.

MeSH terms

Appendiceal Neoplasms* / genetics
Appendiceal Neoplasms* / pathology
Biomarkers, Tumor / genetics
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / pathology
DNA Copy Number Variations
Humans
Microsatellite Instability
Mutation
Peritoneal Neoplasms* / genetics
Peritoneal Neoplasms* / secondary

Substances

Biomarkers, Tumor