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Molecular analyses of 6 different types of uterine smooth muscle tumors: Emphasis in atypical leiomyoma
Author(s) -
Zhang Qing,
Ubago Julianne,
Li Li,
Guo Haiyang,
Liu Yugang,
Qiang Wenan,
Kim J. Julie,
Kong Beihua,
Wei JianJun
Publication year - 2014
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.28900
Subject(s) - pten , leiomyoma , leiomyosarcoma , medicine , smooth muscle tumor , oncology , pathology , pi3k/akt/mtor pathway , biology , signal transduction , genetics
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. Cancer 2014;120:3165–3177. © 2014 American Cancer Society .