GNAS is frequently mutated in both low-grade and high-grade disseminated appendiceal mucinous neoplasms but does not affect survival

Hum Pathol. 2014 Aug;45(8):1737-43. doi: 10.1016/j.humpath.2014.04.018. Epub 2014 May 8.

Abstract

We analyzed a series of 55 disseminated appendiceal mucinous neoplasms treated at our institution for GNAS and KRAS mutations in an attempt to correlate mutation status with clinicopathological findings and patient survival. GNAS mutations (p.R201H, c.602G>A and p.R201C, and c.602C>T) were identified in 17 (31%) of 55 of disseminated mucinous neoplasms and were found in 8 (35%) of 23 low-grade mucinous neoplasms, 7 (37%) of 19 high-grade mucinous adenocarcinomas lacking a signet ring cell component, and 2 (15%) of 13 high-grade mucinous adenocarcinomas with a signet ring cell component. All 7 mucinous adenocarcinomas composed of pure (>95%) signet ring cells harbored wild-type GNAS. There was no significant association between GNAS mutations and sex and age (both with P > .05) or between GNAS mutations and individual adverse histologic features including cytologic grade, destructive invasion, tumor cellularity, angiolymphatic invasion, perineural invasion, and signet ring cells (all with P > .05). KRAS mutations were identified in 22 (40%) of 55 disseminated mucinous neoplasms. GNAS-mutated disseminated appendiceal mucinous neoplasms more frequently harbored concurrent KRAS mutations compared with GNAS wild-type tumors (65% versus 29%, P = .018). GNAS mutations were not significantly associated with overall survival (both with P > .05). Only overall tumor grade was an independent predictor of overall survival in the multivariate analysis (P = .01). Our results indicate that GNAS mutations are frequently identified in both low-grade and high-grade disseminated appendiceal mucinous neoplasms indicating that GNAS mutation status cannot be used to distinguish between low-grade from high-grade appendiceal mucinous neoplasms.

Keywords: Appendix; Disseminated peritoneal adenomucinosis; GNAS; Low-grade mucinous neoplasm; Mucinous adenocarcinoma; Peritoneal mucinous carcinomatosis; Pseudomyxoma peritonei.

MeSH terms

  • Adenocarcinoma, Mucinous / genetics*
  • Adenocarcinoma, Mucinous / mortality
  • Adenocarcinoma, Mucinous / pathology
  • Adult
  • Aged
  • Appendiceal Neoplasms / genetics*
  • Appendiceal Neoplasms / mortality
  • Appendiceal Neoplasms / pathology
  • Chromogranins
  • DNA Mutational Analysis
  • Female
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Prognosis
  • Young Adult

Substances

  • Chromogranins
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs