Racial disparities in molecular subtypes of endometrial cancer

Elizabeth A Dubil; Chunqiao Tian; Guisong Wang; Christopher M Tarney; Nicholas W Bateman; Douglas A Levine; Thomas P Conrads; Chad A Hamilton; George Larry Maxwell; Kathleen M Darcy

doi:10.1016/j.ygyno.2017.12.009

Racial disparities in molecular subtypes of endometrial cancer

Gynecol Oncol. 2018 Apr;149(1):106-116. doi: 10.1016/j.ygyno.2017.12.009.

Affiliations

¹ Gynecologic Cancer Center of Excellence, Department of Obstetrics & Gynecology, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States; Gynecologic Oncology Division, Department of Obstetrics and Gynecology, Naval Medical Center Portsmouth, 620 John Paul Jones Cir, Portsmouth, VA 23708, United States.
² Gynecologic Cancer Center of Excellence, Department of Obstetrics & Gynecology, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States.
³ Gynecologic Cancer Center of Excellence, Department of Obstetrics & Gynecology, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States; John P Murtha Cancer Center, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States.
⁴ Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY 10016, United States.
⁵ Gynecologic Cancer Center of Excellence, Department of Obstetrics & Gynecology, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States; John P Murtha Cancer Center, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States; Inova Schar Cancer Institute, Inova Center for Personalized Health, 3225 Gallows Road, Fairfax, VA 22037, United States.
⁶ Gynecologic Cancer Center of Excellence, Department of Obstetrics & Gynecology, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States; John P Murtha Cancer Center, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States; Inova Schar Cancer Institute, Inova Center for Personalized Health, 3225 Gallows Road, Fairfax, VA 22037, United States; Department of Obstetrics and Gynecology, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA, United States. Electronic address: George.Maxwell@inova.org.
⁷ Gynecologic Cancer Center of Excellence, Department of Obstetrics & Gynecology, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States; John P Murtha Cancer Center, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889, United States. Electronic address: darcyk@whirc.org.

PMID: 29605044
DOI: 10.1016/j.ygyno.2017.12.009

Abstract

Objectives: Racial differences in the molecular subtypes of endometrial cancer and associations with progression-free survival (PFS) were evaluated.

Methods: Molecular, clinical and PFS data were acquired from the Cancer Genome Atlas (TCGA) including classification into the integrative, somatic copy number alteration and transcript-based subtypes. The prevalence and prognostic value of the aggressive molecular subtypes (copy number variant [CNV]-high, cluster 4 or mitotic) were evaluated in Black and White patients.

Results: There were 337 patients including 14% self-designated as Black, 27% with advanced stage, and 82% with endometrioid histology. The CNV-high subtype was more common in Black than White patients (61.9% vs. 23.5%, P=0.0005) and suggested worse PFS in Black patients (hazard ratio [HR]=3.4, P=0.189). The cluster 4 subtype was more prevalent in Black patients (56.8% vs. 20.9%, P<0.0001) and associated with worse PFS in Black patients (HR=3.4, P=0.049). The mitotic subtype was more abundant in Black patients (64.1% vs. 33.7%, P=0.002), indicated worse PFS in Black patients (HR=4.1, P=0.044) including the endometrioid histology (HR=6.1, P=0.024) and exhibited race-associated enrichment in cell cycle signaling and pathways in cancer including PLK1 and BIRC7. All of these aggressive molecular subtypes also indicated worse PFS in White patients, with unique enrichments in mitotic signaling different from Black patients.

Conclusions: The aggressive molecular subtypes from TCGA were more common in Black endometrial cancer patients and indicated worse PFS in both Black and White patients. The mitotic subtypes also indicated worse PFS in Black patients with endometrioid histology. Enrichment patterns in mitotic signaling may represent therapeutic opportunities.

Keywords: Endometrial cancer; Mitotic subtype; Molecular subtypes; Racial disparities.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Black People*
Endometrial Neoplasms / ethnology*
Endometrial Neoplasms / genetics
Endometrial Neoplasms / pathology*
Female
Health Status Disparities*
Humans
Middle Aged
Neoplasm Grading
Neoplasm Staging
Prognosis
White People*