Annals of Surgical Oncology

, Volume 13, Issue 12, pp 1610–1616 | Cite as

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. ZehIII
  • Sydney D. Finkelstein
  • David L. Bartlett



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.


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.


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.


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.


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


  1. 1.
    Sugarbaker PH, Ronnett BM, Archer A, et al. Pseudomyxoma peritonei syndrome. Adv Surg 1996; 30:233–80PubMedGoogle Scholar
  2. 2.
    Ronnett BM, Zahn CM, Kurman RJ, et al. Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis. A clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to “pseudomyxoma peritonei.” Am J Surg Pathol 1995; 19:1390–408PubMedCrossRefGoogle Scholar
  3. 3.
    Ronnett BM, Yan H, Kurman RJ, et al. Patients with pseudomyxoma peritonei associated with disseminated peritoneal adenomucinosis have a significantly more favorable prognosis than patients with peritoneal mucinous carcinomatosis. Cancer 2001; 92:85–91PubMedCrossRefGoogle Scholar
  4. 4.
    Mohamed F, Gething S, Haiba M, et al. Clinically aggressive pseudomyxoma peritonei: a variant of a histologically indolent process. J Surg Oncol 2004; 86:10–5PubMedCrossRefGoogle Scholar
  5. 5.
    Kabbani W, Houlihan PS, Luthra R, et al. Mucinous and nonmucinous appendiceal adenocarcinomas: different clinicopathological features but similar genetic alterations. Mod Pathol 2002; 15:599–605PubMedCrossRefGoogle Scholar
  6. 6.
    Butterworth SA, Panton ON, Klaassen DJ, et al. Morbidity and mortality associated with intraperitoneal chemotherapy for pseudomyxoma peritonei. Am J Surg 2002; 183:529–32PubMedCrossRefGoogle Scholar
  7. 7.
    Deraco M, Baratti D, Inglese MG, et al. Peritonectomy and intraperitoneal hyperthermic perfusion (IPHP): a strategy that has confirmed its efficacy in patients with pseudomyxoma peritonei. Ann Surg Oncol 2004; 11:393–8PubMedCrossRefGoogle Scholar
  8. 8.
    Glehen O, Mohamed F, Gilly FN. Peritoneal carcinomatosis from digestive tract cancer: new management by cytoreductive surgery and intraperitoneal chemohyperthermia. Lancet Oncol 2004; 5:219–28PubMedCrossRefGoogle Scholar
  9. 9.
    Ahmad SA, Kim J, Sussman JJ, et al. Reduced morbidity following cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion. Ann Surg Oncol 2004; 11:387–92PubMedCrossRefGoogle Scholar
  10. 10.
    Popescu NC, Zimonjic DB. Molecular cytogenetic characterization of cancer cell alterations. Cancer Genet Cytogenet 1997; 93:10–21PubMedCrossRefGoogle Scholar
  11. 11.
    Schwab M. Oncogene amplification in solid tumors. Semin Cancer Biol 1999; 9:319–25PubMedCrossRefGoogle Scholar
  12. 12.
    Finkelstein SD, Marsh W, Demetris AJ, et al. Microdissection-based allelotyping discriminates de novo tumor from intrahepatic spread in hepatocellular carcinoma. Hepatology 2003; 37:871–9PubMedCrossRefGoogle Scholar
  13. 13.
    Dreesen JC, Bras M, Coonen E, et al. Allelic dropout caused by allele-specific amplification failure in single-cell PCR of the cystic fibrosis delta F508 deletion. J Assist Reprod Genet 1996; 13:112–4PubMedCrossRefGoogle Scholar
  14. 14.
    Findlay I. Approaches for cystic fibrosis diagnosis. Hum Reprod 1997; 12:166–9PubMedGoogle Scholar
  15. 15.
    Ray PF, Winston RM, Handyside AH. Reduced allele dropout in single-cell analysis for preimplantation genetic diagnosis of cystic fibrosis. J Assist Reprod Genet 1996; 13:103–6CrossRefGoogle Scholar
  16. 16.
    Panteix G, Guillamont M, Cherpin L, et al. Study of the pharmacokinetics of mitomycin C in humans during intraperitoneal chemohyperthermia with special mention of the concentration in local tissues. Oncology 1993; 50:366–70PubMedCrossRefGoogle Scholar
  17. 17.
    Sugarbaker PH. Cytoreductive surgery and intraperitoneal chemotherapy with peritoneal spread of cystadenocarcinoma. Eur J Surg 1991; 561:75–82Google Scholar
  18. 18.
    Sugarbaker PH, Chang D. Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy. Ann Surg Oncol 1999; 6:727–31PubMedCrossRefGoogle Scholar
  19. 19.
    Witkamp AJ, de Bree E, Kaag MM, et al. Extensive surgical cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei. Br J Surg 2001; 88:458–63PubMedCrossRefGoogle Scholar
  20. 20.
    Misdraji J, Yantiss RK, Graeme-Cook FM, et al. Appendiceal mucinous neoplasms: a clinicopathologic analysis of 107 cases. Am J Surg Pathol 2003; 27:1089–103PubMedCrossRefGoogle Scholar
  21. 21.
    Hiraga Y, Tanaka S, Haruma K, et al. Immunoreactive MUC1 expression at the deepest invasive portion correlates with prognosis of colorectal cancer. Oncology 1998; 55:307–19PubMedCrossRefGoogle Scholar
  22. 22.
    Yonezawa S, Sato E. Expression of mucin antigens in human cancers and its relationship with malignancy potential. Pathol Int 1997; 47:813–30PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2006

Authors and Affiliations

  • Vivek Maheshwari
    • 1
  • Allan Tsung
    • 1
  • Yan Lin
    • 2
  • Herb J. ZehIII
    • 1
  • Sydney D. Finkelstein
    • 3
  • David L. Bartlett
    • 1
  1. 1.Department of Surgery, Division of Surgical OncologyUPMC Cancer PavillionPittsburghUSA
  2. 2.Department of BiostatisticsGraduate School of Public Health, University of PittsburghPittsburghUSA
  3. 3.Redpath Integrated Pathology, Inc.PittsburghUSA

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