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Originally published online as doi:10.2353/ajpath.2008.071102 on April 10, 2008

Published online before print April 10, 2008
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(American Journal of Pathology. 2008;172:1403-1410.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.071102

Molecular and Cytogenetic Characterization of Plexiform Leiomyomata Provide Further Evidence for Genetic Heterogeneity Underlying Uterine Fibroids

Jennelle C. Hodge*{dagger}, Bradley J. Quade{dagger}{ddagger}, Mark A. Rubin{dagger}{ddagger}, Elizabeth A. Stewart*, Paola Dal Cin{dagger}{ddagger} and Cynthia C. Morton*{dagger}{ddagger}

From the Department of Obstetrics and Gynecology and Reproductive Biology,* and the Department of Pathology,{ddagger} Brigham and Women’s Hospital, Boston; and Harvard Medical School,{dagger} Boston, Massachusetts

The plexiform variant of uterine leiomyomata (UL) is named for its ribbons or nests of smooth muscle cells that have a rounded, epithelioid shape caused by their entrapment in abundant extracellular matrix. Plexiform UL are currently classified as epithelioid smooth muscle tumors alongside the less predictable, "true" epithelioid tumors (ie, leiomyoblastomas). Karyotypes of six plexiform UL cases were studied, and their abnormalities were found to differ from those of leiomyoblastomas. Analyses using real-time polymerase chain reaction, immunohistochemistry, and fluorescence in situ hybridization demonstrated elevated mRNA and protein levels of the architectural factor HMGA2 and, in some cases, increased DNA copy number. Four of these plexiform UL were profiled with Affymetrix human U133 plus 2.0 expression arrays. Cluster analysis using genes previously shown to discriminate benign and malignant uterine smooth muscle tissues revealed that the plexiform tumors form an isolated group in the benign branch. This is in contrast to an earlier finding in which another variant, cellular UL characterized by loss of a portion of the short arm of chromosome 1, clustered with malignant leiomyosarcomas. These results provide additional evidence of genetic heterogeneity underlying UL of various histological types. We further suggest that plexiform UL should be classified among tumors with extensive hyalinization rather than with "true" epithelioid smooth muscle neoplasms.






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Copyright © 2008 by the American Society for Investigative Pathology.