TY - JOUR
T1 - Molecular analyses of 6 different types of uterine smooth muscle tumors
T2 - Emphasis in atypical leiomyoma
AU - Zhang, Qing
AU - Ubago, Julianne
AU - Li, Li
AU - Guo, Haiyang
AU - Liu, Yugang
AU - Qiang, Wenan
AU - Kim, J. Julie
AU - Kong, Beihua
AU - Wei, Jian Jun
N1 - Publisher Copyright:
© 2014 American Cancer Society.
PY - 2014/10/15
Y1 - 2014/10/15
N2 - 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.
AB - 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.
KW - Atypical leiomyoma
KW - Gene mutations
KW - Leiomyosarcoma
KW - MicroRNA signature
KW - Tumorigenesis
KW - Uterine smooth muscle tumor
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U2 - 10.1002/cncr.28900
DO - 10.1002/cncr.28900
M3 - Article
C2 - 24986214
AN - SCOPUS:84907966535
VL - 120
SP - 3165
EP - 3177
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 20
ER -
