title: BCL-2, in combination with MVP and IGF-1R expression, improves prediction of clinical outcome in complete response cervical carcinoma patients treated by radiochemotherapy.
abstract: OBJECTIVE
  To investigate whether BCL-2 expression would improve MVP/IGF-1R prediction of clinical outcome in cervix carcinoma patients treated by radiochemotherapy, and suggest possible mechanisms behind this effect.
  
  
  METHODS
  Fifty consecutive patients, who achieved complete response to treatment, from a whole series of 60 cases suffering from non-metastatic localized cervical carcinoma, were prospectively included in this study from July 1999 to December 2003. Follow-up was closed in January 2011. All patients received pelvic radiation (45-64.80 Gy in 1.8-2 Gy fractions) with concomitant cisplatin at 40 mg/m2/week doses followed by brachytherapy. Oncoprotein expression was studied by immunohistochemistry in paraffin-embedded tumour tissue.
  
  
  RESULTS
  No relation was found between BCL-2 and clinicopathological variables. High MVP/IGF-1R/BCL-2 tumour expression was strongly related to poor local and regional disease-free survival (P<0.0001), distant disease-free survival (P=0.010), disease-free survival (P<0.0001), and cause-specific survival (P<0.0001). NHEJ repair protein Ku70/80 expression was significantly repressed in tumours overexpressing all three oncoproteins (P=0.047). No differences were observed in proliferation (Ki67 expression) or P53 alteration.
  
  
  CONCLUSIONS
  BCL-2, MVP, and IGF-1R overexpression were related to poorer clinical outcome in cervical cancer patients who achieved clinical complete response to radiochemotherapy. The NHEJ repair protein Ku70/80 expression could be involved in the regulation of these oncoproteins.
authors.affiliation: Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain. lhenriquez@dcc.ulpgc.es
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Henríquez-Hernández
authors.forename: Marta
authors.initials: M
authors.lastname: Lloret
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pinar
authors.forename: Elisa
authors.initials: E
authors.lastname: Bordón
authors.forename: Agustín
authors.initials: A
authors.lastname: Rey
authors.forename: Amina
authors.initials: A
authors.lastname: Lubrano
authors.forename: Pedro Carlos
authors.initials: PC
authors.lastname: Lara
mesh_terms: D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D000072200:Ku Autoantigen; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy / Q000628:therapy*; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis*; D000099187:Major Vault Protein
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D000072200:Ku Autoantigen; D019253:Proto-Oncogene Proteins c-bcl-2; D017526:Receptor, IGF Type 1; D016159:Tumor Suppressor Protein p53; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C495901:TP53 protein, human; C000606509:Xrcc6 protein, human