title: EZH2 and ALDH1 expression in ductal carcinoma in situ: complex association with recurrence and progression to invasive breast cancer.
abstract: The diagnosis of ductal carcinoma in situ (DCIS) is an increasingly common event due to widespread use of screening mammography. However, appropriate clinical management of DCIS is a major challenge in the absence of prognostic markers. Tumor-initiating cells may be particularly relevant for disease pathogenesis; therefore, two markers associated with such cells, EZH2 and ALDH1, were evaluated. A cohort of 248 DCIS patients was used to determine the association of EZH2 and ALDH1 with ipsilateral breast event, DCIS recurrence and progression to invasive breast cancer (IBC). In this cohort, high EZH2 expression was associated with the risk of an ipsilateral breast event and DCIS recurrence but not invasive progression. ALDH1 expression was observed in both the tumor and stromal compartment; however, in neither compartment were ALDH1 levels independently associated with evaluated study endpoints. Interestingly, the combination of high EZH2 with high epithelial ALDH1 was associated with disease progression. Therefore, ALDH1 within the DCIS lesion can add to the prognostic significance of EZH2, particularly in the context of risk of development of invasive disease.
authors.affiliation: Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Erik S
authors.initials: ES
authors.lastname: Knudsen
authors.forename: Ornella
authors.initials: O
authors.lastname: Dervishaj
authors.forename: Celina G
authors.initials: CG
authors.lastname: Kleer
authors.forename: Thomas
authors.initials: T
authors.lastname: Pajak
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Schwartz
authors.forename: Agnieszka K
authors.initials: AK
authors.lastname: Witkiewicz
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology* / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000201:enzymology*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
keywords: ALDH1; DCIS; EZH2; IBC; ductal carcinoma in situ; invasive breast cancer; prognostic markers; tumor-initiating cells