Molecular analyses of 6 different types of uterine smooth muscle tumors: Emphasis in atypical leiomyoma

Qing Zhang, Julianne Ubago, Li Li, Haiyang Guo, Yugang Liu, Wenan Qiang, J. Julie Kim, Beihua Kong*, Jian Jun Wei

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

BACKGROUND: Uterine smooth muscle tumors (USMTs) constitute a group of histologic, genetic, and clinical heterogeneous tumors that include at least 6 major histologically defined tumor types: leiomyoma (ULM), mitotically active leiomyoma (MALM), cellular leiomyoma (CLM), atypical leiomyoma (ALM), uncertain malignant potential (STUMP), and leiomyosarcoma (LMS). Apart from ULM and LMS, the nature of these variants is not well defined.

METHODS: A total of 167 cases of different USMT variants were collected, reviewed, and diagnostically confirmed based on the World Health Organization and Stanford schemes. These included 38 cases of LMS, 18 cases of STUMP, 42 cases of ALM, 22 cases of CLM, 7 cases of MALM, and 40 cases of ULM. Molecular analysis included selected microRNAs (miRNAs), oncogenes, and tumor suppressors that are highly relevant to USMT.

RESULTS: Overall, 49% (17/35) of LMS cases and 7% (1/14) of STUMP cases died due to their USMT, but no deaths were attributed to ALM. miRNA profiling revealed that ALM and LMS shared similar miRNA signatures. P53 mutations and PTEN deletions were significantly higher in LMS, ALM, and STUMP compared with other USMT variants (P<.01). In contrast, MED12 mutations were extremely common in ULM and MALM (>74%) but were significantly less common (<15%) in CLM, ALM, STUMP, and LMS (P<.01).

CONCLUSION: Six types of USMT have different gene mutation fingerprints. ALM shares many molecular alterations with LMS. Our findings suggest that ALM may be a precursor lesion of LMS or have similar genetic changes during its early stage.

Original languageEnglish (US)
Pages (from-to)3165-3177
Number of pages13
JournalCancer
Volume120
Issue number20
DOIs
StatePublished - Oct 15 2014

Keywords

  • Atypical leiomyoma
  • Gene mutations
  • Leiomyosarcoma
  • MicroRNA signature
  • Tumorigenesis
  • Uterine smooth muscle tumor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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