Fumarate Hydratase Mutations and Alterations in Leiomyoma With Bizarre Nuclei.

Abstract

Leiomyoma with bizarre nuclei (LM-BN), is a variant of uterine smooth muscle tumor with atypical histologic features. Although some LM-BN share several significant genetic alterations with leiomyosarcoma, including p16 and p53, the underlying tumorigenesis of LM-BN remains largely unknown. As we previously reported, LM-BN can be divided into 2 subtypes, type I and type II, based on different nuclear features. Type I LM-BN have similar histologic features as uterine smooth muscle tumors with fumarate hydratase (FH) alterations. In this study, we examined FH expression and FH mutations in 77 LM-BN (40 type I cases and 37 type II cases). FH expression was examined by immunohistochemistry using S-(2-succino)-cysteine antibodies (2SC, a protein modification associated with FH inactivation and subsequent fumarate accumulation) and FH antibodies (FH gene products). Seventy-two LM-BN tumors underwent Sanger sequencing to detect FH mutations. We found that 51% (39/77) of LM-BN showed FH alterations detected by immunohistochemistry with both 2SC and FH. Mutational analysis showed that 21% (15/72) of LM-BN harbored FH gene mutations. Further analysis revealed that 85% (34/40) of those with FH alterations were type I LM-BN while 19% (7/37) were type II LM-BN. Our findings suggest that over half of histologically diagnosed LM-BN may be related to FH alterations or FH mutations and the majority of these have the characteristic histologic features of type I LM-BN.

• Authors: Qing Zhang, Kate Poropatich, Julianne Ubago, Jia Xie, Xiuhua Xu, Norma Frizzell, Julie Kim, Beihua Kong, Jian-Jun Wei
• Journal: International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists (Int J Gynecol Pathol) Vol. 37 Issue 5 Pg. 421-430 (Sep 2018) ISSN: 1538-7151 [Electronic] United States
• PMID: 28863073 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Fumarate Hydratase

Topics

• Adult
• Aged
• Biomarkers, Tumor (analysis)
• Cell Nucleus (pathology)
• DNA Mutational Analysis
• Female
• Fumarate Hydratase (genetics)
• Humans
• Leiomyoma (enzymology, genetics, pathology)
• Middle Aged
• Mutation
• Uterine Neoplasms (enzymology, genetics, pathology)
• Young Adult