Analysis of loss of heterozygosity for tumor-suppressor genes can accurately classify and predict the clinical behavior of mucinous tumors arising from the appendix

Vivek Maheshwari, Allan Tsung, Yan Lin, Herb J. Zeh, Sydney D. Finkelstein, David L. Bartlett

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Background: Pseudomyxoma peritonei is a rare heterogenous clinical syndrome with a variable clinical course. On the basis of the hypothesis that cumulative mutational damage can predict biological aggressiveness, we evaluated the utility of integrated histopathology and molecular analysis for patients with pseudomyxoma peritonei syndrome. Methods: Tissue specimens from 23 mucinous appendiceal tumors were analyzed. DNA samples from multiple sites were analyzed for loss of heterozygosity by using a panel of 15 allelic loss microsatellite markers and K-ras-2 point mutational damage. The fractional mutational rate (FMR), determined as the number of mutated markers divided by the total number of informative markers, was calculated by using the six most informative markers and the K-ras-2 gene. Kappa statistics were calculated to test the association between FMR and the histopathologic classification. Results: Our study included 6 female and 17 male patients with a mean age of 53.6 years and a mean survival of 43.9 months. We found an association between tumor loss of heterozygosity markers and histopathologic classification (P < .05). In addition, there was also an association between the FMR and pathological classification as well as between the FMR and survival (P < .05). An FMR less than .25 indicated low-grade disease, an FMR of .25 to .50 indicated intermediate grade, and an FMR greater than .5 indicated a high-grade tumor. Conclusions: Mutational profiling of accumulated allelic loss and point mutational damage correlated strongly with histopathologic definitions of pseudomyxoma peritonei disease and helped to predict the prognosis of these patients. FMR, along with histopathology, offers a comprehensive classification of these rare tumors.

Original languageEnglish (US)
Pages (from-to)1610-1616
Number of pages7
JournalAnnals of Surgical Oncology
Volume13
Issue number12
DOIs
StatePublished - Dec 1 2006
Externally publishedYes

Keywords

  • Appendix
  • Disseminated peritoneal adenomucinosis
  • Loss of heterozygosity
  • Peritoneal mucinous carcinomatosis
  • Pseudomyxoma peritonei

ASJC Scopus subject areas

  • Surgery
  • Oncology

Fingerprint Dive into the research topics of 'Analysis of loss of heterozygosity for tumor-suppressor genes can accurately classify and predict the clinical behavior of mucinous tumors arising from the appendix'. Together they form a unique fingerprint.

  • Cite this