BCL-2, in combination with MVP and IGF-1R expression, improves prediction of clinical outcome in complete response cervical carcinoma patients treated by radiochemotherapy

Gynecol Oncol. 2011 Sep;122(3):585-9. doi: 10.1016/j.ygyno.2011.05.037. Epub 2011 Jun 25.

Abstract

Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Nuclear / biosynthesis
  • DNA-Binding Proteins / biosynthesis
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / biosynthesis
  • Ku Autoantigen
  • Middle Aged
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Receptor, IGF Type 1 / biosynthesis*
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / biosynthesis
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / radiotherapy
  • Uterine Cervical Neoplasms / therapy*
  • Vault Ribonucleoprotein Particles / biosynthesis*

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • Receptor, IGF Type 1
  • Xrcc6 protein, human
  • Ku Autoantigen