The Incorporation of Genomic Testing to the Evaluation of Appendiceal Mucinous Neoplasms Improves the Prognostic Classification of Patients with Disseminated Disease

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Conference Proceeding

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Publication Title

Mod Pathol


Background: Disseminated appendiceal mucinous neoplasms (AMNs) are a heterogeneous group of tumors with variable clinical behavior. Several studies have shown that the prognosis of disseminated AMNs is highly dependent on histologic grade as defined by the American Joint Cancer Conference (AJCC). Recently, comprehensive genomic profiling has elucidated the genomic landscape of AMNs; however, it's unclear if molecular testing can further stratify clinical outcome among patients with disseminated disease. Therefore, we evaluated the clinicopathologic and genomic features of 114 patients with disseminated AMN. Design: Tumors from consecutive patients with disseminated disease from 2016 to 2020 were analyzed by targeted nextgeneration sequencing of 28 genes associated with gastrointestinal tract neoplasms. Genomic alterations were correlated with several clinicopathologic findings, such as AJCC grade, lymphovascular and perineural invasion, regional lymph node metastases, peritoneal cancer index (PCI), cytoreductive surgery (CRS), completeness of cytoreduction (CC) score, hyperthermic intraperitoneal chemotherapy (HIPEC) treatment, and overall survival (OS). Results: Genomic alterations were identified in 110 of 114 (96%) disseminated AMNs. In descending order, the most prevalent genomic alterations were found in KRAS (82%), GNAS (61%), TP53 (25%), SMAD4 (21%), the mTOR genes (PIK3CA and PTEN, 8%), and CDKN2A (2%). No statistically significant clinicopathologic findings were associated with KRAS and/or GNAS mutations. However, collectively, alterations in TP53, SMAD4, CDKN2A, and the mTOR genes correlated with higher AJCC grade (G2/G3, 79% vs. 45%, p<0.001), lymphovascular invasion (30% vs. 11%, p=0.014), and perineural invasion (23% and 6%, p=0.011). In addition, the 3-year and 5-year OS rates for AMN patients with TP53, SMAD4, CDKN2A, and/or mTOR gene alterations were 71% and 48%, respectively, as compared with 88% and 83%, respectively, for patients that were wild-type for the aforementioned genes. By multivariate analysis, alterations in TP53, SMAD4, CDKN2A, and/or the mTOR genes in AMNs were a negative prognostic factor for OS and independent of AJCC grade, lymphovascular invasion, perineural invasion, PCI, CRS, CC score, and HIPEC treatment (p=0.029). Conclusions: Genomic alterations in TP53, SMAD4, CDKN2A, and the mTOR genes in disseminated AMNs correlate with adverse clinicopathologic features and poor patient OS. Thus, molecular testing may aid in the prognostication of AMN patients with disseminated disease.

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Not assigned.





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