title: Analysis of loss of heterozygosity for tumor-suppressor genes can accurately classify and predict the clinical behavior of mucinous tumors arising from the appendix.
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.
authors.affiliation: Department of Surgery, Division of Surgical Oncology, UPMC Cancer Pavillion, 5150 Centre Avenue, Room 415, Pittsburgh, Pennsylvania 15232, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Maheshwari
authors.forename: Allan
authors.initials: A
authors.lastname: Tsung
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Herb J
authors.initials: HJ
authors.lastname: Zeh
authors.forename: Sydney D
authors.initials: SD
authors.lastname: Finkelstein
authors.forename: David L
authors.initials: DL
authors.lastname: Bartlett
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001063:Appendiceal Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D017354:Point Mutation; D011553:Pseudomyxoma Peritonei / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm