Expanding upon the Human Myometrial Stem Cell Hypothesis and the Role of Race, Hormones, Age, and Parity in a Profibroid Environment

Lauren E. Prusinski Fernung, Kimya Jones, Aymara Mas, Daniel T Kleven, Jennifer L Waller, Ayman Al-Hendy

Research output: Contribution to journalArticle

Abstract

Uterine fibroids (UFs) are clonal, hormonally regulated, benign smooth-muscle myometrial tumors that severely affect female reproductive health, although their unknown etiology limits effective care. UFs occur fourfold more commonly in African American women than in Caucasian women, and African American women generally have earlier disease onset and greater UF tumor burden, although the mechanism of this ethnic disparity has not been identified. Recent findings have linked cancer (ie, tumor) risk to increased tissue-specific stem cell division and self-renewal and suggest that somatic mutations in myometrial stem cells (MyoSCs) convert them into tumor-initiating cells, leading to UF. Specifically, preliminary results in paraffin-embedded myometrial tissues have shown increased STRO-1+/CD44+ MyoSCs in African American versus Caucasian women. Using specific methods of flow cytometry and automated quantitative pathology imaging, a large cohort of myometrial samples were investigated to determine how the STRO-1+/CD44+ MyoSCs change with regard to a patient's race, age, parity, fibroid and hormone statuses, and the location of UFs within the uterus. We confirmed that the STRO-1+/CD44+ MyoSC population is expanded in African American women, is correlated with parity and fibroid number, and fluctuates with cyclic menstrual cycle hormone changes and age. Our data suggest that an expanded MyoSC population increases the formation of tumor-initiating cells, ultimately contributing to increased UF prevalence and burden in African American women.

Original languageEnglish (US)
Pages (from-to)2293-2306
Number of pages14
JournalAmerican Journal of Pathology
Volume188
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

Leiomyoma
Parity
Stem Cells
Hormones
African Americans
Neoplastic Stem Cells
Smooth Muscle Tumor
Reproductive Health
Menstrual Cycle
Tumor Burden
Cell Division
Paraffin
Population
Neoplasms
Flow Cytometry
Pathology
Mutation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Expanding upon the Human Myometrial Stem Cell Hypothesis and the Role of Race, Hormones, Age, and Parity in a Profibroid Environment. / Prusinski Fernung, Lauren E.; Jones, Kimya; Mas, Aymara; Kleven, Daniel T; Waller, Jennifer L; Al-Hendy, Ayman.

In: American Journal of Pathology, Vol. 188, No. 10, 01.10.2018, p. 2293-2306.

Research output: Contribution to journalArticle

Prusinski Fernung, Lauren E. ; Jones, Kimya ; Mas, Aymara ; Kleven, Daniel T ; Waller, Jennifer L ; Al-Hendy, Ayman. / Expanding upon the Human Myometrial Stem Cell Hypothesis and the Role of Race, Hormones, Age, and Parity in a Profibroid Environment. In: American Journal of Pathology. 2018 ; Vol. 188, No. 10. pp. 2293-2306.
@article{cedbb310fc8c4b65826ce3701ef3eed9,
title = "Expanding upon the Human Myometrial Stem Cell Hypothesis and the Role of Race, Hormones, Age, and Parity in a Profibroid Environment",
abstract = "Uterine fibroids (UFs) are clonal, hormonally regulated, benign smooth-muscle myometrial tumors that severely affect female reproductive health, although their unknown etiology limits effective care. UFs occur fourfold more commonly in African American women than in Caucasian women, and African American women generally have earlier disease onset and greater UF tumor burden, although the mechanism of this ethnic disparity has not been identified. Recent findings have linked cancer (ie, tumor) risk to increased tissue-specific stem cell division and self-renewal and suggest that somatic mutations in myometrial stem cells (MyoSCs) convert them into tumor-initiating cells, leading to UF. Specifically, preliminary results in paraffin-embedded myometrial tissues have shown increased STRO-1+/CD44+ MyoSCs in African American versus Caucasian women. Using specific methods of flow cytometry and automated quantitative pathology imaging, a large cohort of myometrial samples were investigated to determine how the STRO-1+/CD44+ MyoSCs change with regard to a patient's race, age, parity, fibroid and hormone statuses, and the location of UFs within the uterus. We confirmed that the STRO-1+/CD44+ MyoSC population is expanded in African American women, is correlated with parity and fibroid number, and fluctuates with cyclic menstrual cycle hormone changes and age. Our data suggest that an expanded MyoSC population increases the formation of tumor-initiating cells, ultimately contributing to increased UF prevalence and burden in African American women.",
author = "{Prusinski Fernung}, {Lauren E.} and Kimya Jones and Aymara Mas and Kleven, {Daniel T} and Waller, {Jennifer L} and Ayman Al-Hendy",
year = "2018",
month = "10",
day = "1",
doi = "10.1016/j.ajpath.2018.06.023",
language = "English (US)",
volume = "188",
pages = "2293--2306",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "10",

}

TY - JOUR

T1 - Expanding upon the Human Myometrial Stem Cell Hypothesis and the Role of Race, Hormones, Age, and Parity in a Profibroid Environment

AU - Prusinski Fernung, Lauren E.

AU - Jones, Kimya

AU - Mas, Aymara

AU - Kleven, Daniel T

AU - Waller, Jennifer L

AU - Al-Hendy, Ayman

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Uterine fibroids (UFs) are clonal, hormonally regulated, benign smooth-muscle myometrial tumors that severely affect female reproductive health, although their unknown etiology limits effective care. UFs occur fourfold more commonly in African American women than in Caucasian women, and African American women generally have earlier disease onset and greater UF tumor burden, although the mechanism of this ethnic disparity has not been identified. Recent findings have linked cancer (ie, tumor) risk to increased tissue-specific stem cell division and self-renewal and suggest that somatic mutations in myometrial stem cells (MyoSCs) convert them into tumor-initiating cells, leading to UF. Specifically, preliminary results in paraffin-embedded myometrial tissues have shown increased STRO-1+/CD44+ MyoSCs in African American versus Caucasian women. Using specific methods of flow cytometry and automated quantitative pathology imaging, a large cohort of myometrial samples were investigated to determine how the STRO-1+/CD44+ MyoSCs change with regard to a patient's race, age, parity, fibroid and hormone statuses, and the location of UFs within the uterus. We confirmed that the STRO-1+/CD44+ MyoSC population is expanded in African American women, is correlated with parity and fibroid number, and fluctuates with cyclic menstrual cycle hormone changes and age. Our data suggest that an expanded MyoSC population increases the formation of tumor-initiating cells, ultimately contributing to increased UF prevalence and burden in African American women.

AB - Uterine fibroids (UFs) are clonal, hormonally regulated, benign smooth-muscle myometrial tumors that severely affect female reproductive health, although their unknown etiology limits effective care. UFs occur fourfold more commonly in African American women than in Caucasian women, and African American women generally have earlier disease onset and greater UF tumor burden, although the mechanism of this ethnic disparity has not been identified. Recent findings have linked cancer (ie, tumor) risk to increased tissue-specific stem cell division and self-renewal and suggest that somatic mutations in myometrial stem cells (MyoSCs) convert them into tumor-initiating cells, leading to UF. Specifically, preliminary results in paraffin-embedded myometrial tissues have shown increased STRO-1+/CD44+ MyoSCs in African American versus Caucasian women. Using specific methods of flow cytometry and automated quantitative pathology imaging, a large cohort of myometrial samples were investigated to determine how the STRO-1+/CD44+ MyoSCs change with regard to a patient's race, age, parity, fibroid and hormone statuses, and the location of UFs within the uterus. We confirmed that the STRO-1+/CD44+ MyoSC population is expanded in African American women, is correlated with parity and fibroid number, and fluctuates with cyclic menstrual cycle hormone changes and age. Our data suggest that an expanded MyoSC population increases the formation of tumor-initiating cells, ultimately contributing to increased UF prevalence and burden in African American women.

UR - http://www.scopus.com/inward/record.url?scp=85053764535&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053764535&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2018.06.023

DO - 10.1016/j.ajpath.2018.06.023

M3 - Article

C2 - 30075150

AN - SCOPUS:85053764535

VL - 188

SP - 2293

EP - 2306

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 10

ER -