title: Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients.
abstract: Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P=0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P=0.013), mitotic index (P=0.032), and Nottingham Prognostic Index score (P=0.014). Ecd expression was positively associated with HER2/neu (P=0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P=0.008) and disease-free survival (DFS) (P=0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198-5805, USA.
authors.forename: Xiangshan
authors.initials: X
authors.lastname: Zhao
authors.forename: Sameer
authors.initials: S
authors.lastname: Mirza
authors.forename: Alaa
authors.initials: A
authors.lastname: Alshareeda
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Channabasavaiah Basavaraju
authors.initials: CB
authors.lastname: Gurumurthy
authors.forename: Aditya
authors.initials: A
authors.lastname: Bele
authors.forename: Jun Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Shakur
authors.initials: S
authors.lastname: Mohibi
authors.forename: Monica
authors.initials: M
authors.lastname: Goswami
authors.forename: Subodh M
authors.initials: SM
authors.lastname: Lele
authors.forename: William
authors.initials: W
authors.lastname: West
authors.forename: Fang
authors.initials: F
authors.lastname: Qiu
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: Emad A
authors.initials: EA
authors.lastname: Rakha
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
authors.forename: Hamid
authors.initials: H
authors.lastname: Band
authors.forename: Vimla
authors.initials: V
authors.lastname: Band
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C513410:ECD protein, human; C508053:ERBB2 protein, human