EZH2 and ALDH1 expression in ductal carcinoma in situ: complex association with recurrence and progression to invasive breast cancer. 2013

Erik S Knudsen, and Ornella Dervishaj, and Celina G Kleer, and Thomas Pajak, and Gordon F Schwartz, and Agnieszka K Witkiewicz
Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA.

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.

UI MeSH Term Description Entries
D007527 Isoenzymes Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics. Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009361 Neoplasm Invasiveness Ability of neoplasms to infiltrate and actively destroy surrounding tissue. Invasiveness, Neoplasm,Neoplasm Invasion,Invasion, Neoplasm
D009364 Neoplasm Recurrence, Local The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site. Local Neoplasm Recurrence,Local Neoplasm Recurrences,Locoregional Neoplasm Recurrence,Neoplasm Recurrence, Locoregional,Neoplasm Recurrences, Local,Recurrence, Local Neoplasm,Recurrence, Locoregional Neoplasm,Recurrences, Local Neoplasm,Locoregional Neoplasm Recurrences,Neoplasm Recurrences, Locoregional,Recurrences, Locoregional Neoplasm
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D002285 Carcinoma, Intraductal, Noninfiltrating A noninvasive (noninfiltrating) carcinoma of the breast characterized by a proliferation of malignant epithelial cells confined to the mammary ducts or lobules, without light-microscopy evidence of invasion through the basement membrane into the surrounding stroma. Carcinoma, Intraductal,DCIS,Ductal Carcinoma In Situ,Atypical Ductal Hyperplasia,Intraductal Carcinoma, Noninfiltrating,Atypical Ductal Hyperplasias,Carcinoma, Noninfiltrating Intraductal,Carcinomas, Intraductal,Carcinomas, Noninfiltrating Intraductal,Ductal Hyperplasia, Atypical,Ductal Hyperplasias, Atypical,Hyperplasia, Atypical Ductal,Hyperplasias, Atypical Ductal,Intraductal Carcinoma,Intraductal Carcinomas,Intraductal Carcinomas, Noninfiltrating,Noninfiltrating Intraductal Carcinoma,Noninfiltrating Intraductal Carcinomas
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071221 Enhancer of Zeste Homolog 2 Protein A histone-lysine N-methyltransferase and catalytic subunit of Polycomb Repressive Complex 2. It methylates LYSINE 9 (H3K9me) and LYSINE 27 (H3K27me) of HISTONE H3, leading to transcriptional repression of the affected target gene. EZH2 also methylates non-histone proteins such as GATA4 TRANSCRIPTION FACTOR and the nuclear receptor RORA. It regulates CIRCADIAN CLOCKS via histone methylation of circadian protein gene PROMOTER REGIONS, and its repressive activity is also important for the identity and differentiation of EMBRYONIC STEM CELLS. Enhancer of Zeste Homolog 2,Histone-Lysine N-Methyltransferase EZH2,Lysine N-Methyltransferase-6,EZH2, Histone-Lysine N-Methyltransferase,Histone Lysine N Methyltransferase EZH2,Lysine N Methyltransferase 6
D000080924 Aldehyde Dehydrogenase 1 Family A subfamily of the aldehyde dehydrogenase family of enzymes involved in the synthesis of acetate from ethanol. ALDH1 Enzyme,Acetaldehyde Dehydrogenase 1,Aldehyde Dehydrogenase 1

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