title: Decreased PLK1 expression denotes therapy resistance and unfavourable disease-free survival in rectal cancer patients receiving neoadjuvant chemoradiotherapy.
abstract: OBJECTIVE
  Polo-like kinase 1 (Plk1) plays a key role in mitotic cell division and DNA damage repair. It has been observed that either up-regulated or down-regulated Plk1 could induce mitotic defects that results in aneuploidy and tumorigenesis, probably depending on the context. Few previous reports have associated Plk1 expression with prognosis and response to radiotherapy in rectal carcinomas. The aim of this study is to investigate the prognostic impact of Plk1 expression and its role in predicting response to neoadjuvant cheomoradiotherapy in rectal cancer.
  
  
  RESULTS
  Immunohistochemical analysis of Plk1 expression was performed in the pre-treatment tumour specimens from 75 rectal cancer patients. We analysed the assocation between Plk1 expression and clinicopathological parameters, pathologic response and outcome. Opposed to previous reports on this issue, low expression of Plk1 was significantly associated with a high grade of differentiation (P=0.0007) and higher rate of distant metastasis (P=0.014). More importantly, decreased levels of Plk1 were associated with absence of response after neoadjuvant therapy (P=0.049). Moreover, low Plk1 expression emerged as an unfavourable prognostic factor for disease-free survival in the non-responder group of patients (P=0.037).
  
  
  CONCLUSIONS
  Decreased Plk1 expression was associated with poor pathologic response and worse disease-free survival in rectal cancer patients receiving neoadjuvant chemoradiotherapy, suggesting Plk1 as a clinically relevant marker to predict chemoradiotherapy response and outcome.
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", 28040 Madrid Spain. Electronic address: arancha.cebrian@fjd.es.
authors.forename: Arancha
authors.initials: A
authors.lastname: Cebrián
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", 28040 Madrid Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gómez Del Pulgar
authors.affiliation: Pathology Department, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", 28040 Madrid Spain.
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Fernández-Aceñero
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", 28040 Madrid Spain.
authors.forename: Aurea
authors.initials: A
authors.lastname: Borrero-Palacios
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", 28040 Madrid Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Del Puerto-Nevado
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", 28040 Madrid Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Useros
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", 28040 Madrid Spain.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Marín-Arango
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", 28040 Madrid Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Caramés
authors.affiliation: Pathology Department, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", 28040 Madrid Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Vega-Bravo
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", 28040 Madrid Spain.
authors.forename: María
authors.initials: M
authors.lastname: Rodríguez-Remírez
authors.affiliation: Pathology Department, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", 28040 Madrid Spain.
authors.forename: Felix
authors.initials: F
authors.lastname: Manzarbeitia
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", 28040 Madrid Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Foncillas
mesh_terms: D000368:Aged; D018797:Cell Cycle Proteins / Q000378:metabolism*; D059186:Chemoradiotherapy, Adjuvant; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000532:radiotherapy; D015996:Survival Rate; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1
keywords: Chemoradiotherapy; Polo-like kinase 1; Predictive marker; Rectal cancer; Risk factor