title: The prognostic significance of PELP1 expression in invasive breast cancer with emphasis on the ER-positive luminal-like subtype.
abstract: The transcription functions of oestrogen receptors (ER) are influenced by several coregulators such as PELP1 (proline, glutamate and leucine rich protein 1). The aim of the present study, which uses tissue microarrays and immunohistochemistry, is to explore the clinical and biological relevance of PELP1 protein expression in a large series of consecutive patients (1,162 patients) with invasive breast cancers with particular emphasis on its role in the ER-positive/luminal-like class of tumours. Our results showed that increased PELP1 expression is associated with tumours of larger size, higher histological grade, higher mitotic count, and with positive expression of basal cytokeratins (CK) (CK14; P = 0.018 and CK5/6; P = 0.029), P-cadherin (P = 0.002), p53 and MIB1 (P = 0.018). There was an inverse association between PELP1 expression and ER (P = 0.002), progesterone (PgR) (P = 0.004), androgen (AR) receptor (P < 0.001), and luminal CK (CK18; P = 0.027) expression. A significant association between PELP1 expression and shorter breast cancer specific survival (BCSS) (P = 0.002) and disease-free survival (DFI) (P = 0.006) was found. Multivariate Cox hazard analysis showed that PELP1 expression was an independent predictor of shorter BCSS (Hazard ratio (HR) = 1.349, P = 0.006) and shorter DFI (HR = 1.255, P = 0.011). In the ER-positive/luminal-like group (n = 768), PELP1 expression showed similar association with other clinicopathological variables and was an independent predictor of shorter DFI (HR = 1.256, P = 0.036). In conclusion, PELP1 protein expression is an independent prognostic predictor of shorter BCSS and DFI in breast cancer and its elevated expression is positively associated with markers of poor outcome. PELP1 appears to have a potential application in assessing the clinical outcome of patients with ER-positive breast cancer.
authors.affiliation: Department of Histopathology, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, University of Nottingham, Hucknall Road, Nottingham, UK.
authors.forename: Hany Onsy
authors.initials: HO
authors.lastname: Habashy
authors.forename: Desmond G
authors.initials: DG
authors.lastname: Powe
authors.forename: Emad A
authors.initials: EA
authors.lastname: Rakha
authors.forename: Graham
authors.initials: G
authors.lastname: Ball
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Macmillan
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D056970:Co-Repressor Proteins; D018572:Disease-Free Survival; D004967:Estrogens; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007633:Keratins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D008940:Mitotic Index; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators / Q000032:analysis / Q000502:physiology*; D014157:Transcription Factors; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D015820:Cadherins; D056970:Co-Repressor Proteins; D004967:Estrogens; D009363:Neoplasm Proteins; C438485:PELP1 protein, human; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D007633:Keratins; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases