The selected biomarker analysis in 5 types of uterine smooth muscle tumors

Qing Zhang, Margaux Jenna Kanis, Julianne Ubago, Dachao Liu, Denise M. Scholtens, Anna E. Strohl, John R. Lurain, Shohreh Shahabi, Beihua Kong, Jian Jun Wei*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Uterine smooth muscle tumors (USMTs) consist of a group of histologically heterogeneous and clinically diverse diseases ranging from malignant leiomyosarcoma (LMS) to benign leiomyoma (ULM). The genetic alterations in LMS are complex, with some genetic alterations present in both LMS and other atypical histologic variants of USMT. In this study, we reviewed 119 USMTs with a diagnosis of LMS, smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, and cellular leiomyoma, as well as 46 ULMs and 60 myometrial controls. We selected 17 biomarkers highly relevant to LMS in 4 tumorigenic pathways including steroid hormone receptors (estrogen receptor [ER] and progesterone receptor [PR]), cell cycle/tumor suppressor genes, AKT pathway markers, and associated oncogenes. ER and PR expression was significantly lower in LMS than smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, cellular leiomyoma, and ULM (P <.01). Sixty-five percent of LMSs showed complete loss of ER, and 75% of LMSs showed complete loss of PR. All cell cycle genes were differentially expressed in different types of tumor, but significant overlap was noted. More than 75% of LMSs had Ki-67 index greater than 33%, and only 5% in all other types of USMT. Expression of the selected oncogenes varied widely among different types of USMT. PR positivity and p53 had a borderline association with progression-free survival (P =.055 for PR and P =.0847 for p53). Furthermore, high PR expression was significantly associated with a longer overall survival (P =.0163, hazard ratio 0.198). Cell proliferative indices (Ki-67) and sex steroid hormone receptors were the most valuable markers in differentiating LMS from other USMT variants.

Original languageEnglish (US)
Pages (from-to)17-27
Number of pages11
JournalHuman pathology
Volume76
DOIs
StatePublished - Jun 2018

Keywords

  • Atypical smooth muscle tumor
  • Biomarker
  • Clinical correlation
  • Immunohistochemistry
  • Leiomyosarcoma
  • Uterine smooth muscle tumor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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