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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 12/2006

01-12-2006

Analysis of Loss of Heterozygosity for Tumor-Suppressor Genes Can Accurately Classify and Predict the Clinical Behavior of Mucinous Tumors Arising From the Appendix

Authors: Vivek Maheshwari, MD, Allan Tsung, MD, Yan Lin, PhD, Herb J. Zeh III, MD, Sydney D. Finkelstein, David L. Bartlett, MD

Published in: Annals of Surgical Oncology | Issue 12/2006

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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.
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Metadata
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
Authors
Vivek Maheshwari, MD
Allan Tsung, MD
Yan Lin, PhD
Herb J. Zeh III, MD
Sydney D. Finkelstein
David L. Bartlett, MD
Publication date
01-12-2006
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 12/2006
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-006-9081-1

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