title: Epstein-Barr virus latent membrane protein 1 (EBV-LMP1) and tumor proliferation rate as predictive factors of nasopharyngeal cancer (NPC) radiation response.
abstract: BACKGROUND
  Irradiation is still the treatment of choice in NPC treatment as one of highest malignancy in Indonesia as well as in Southeast Asia. Up to now there is no accurate predictor on radiation response, since that the similar histo-morphological pattern, as a well-known prognostic factor can revealed a wide range of treatment outcomes. Purpose of the study is to established the influence of EBV-LMP 1 as the most important protein expressed by EBV oncogenes in cellular behaviour such as proliferation rate, tumor aggressivity in NPC and to find out the role of both, proliferation rate and EBV-LMP1 expression as a predictor on NPC radiation response.
  
  
  METHODS
  172 paraffin-embedded biopsy specimens from NPC patients were analysed flow-cytometrically to obtain the S-phase fraction value as the proliferation parameter. From this group of patients, 81 fresh specimen biopsies could be collected, and the EBV-LMP 1 expression were detected by western blotting technique (mAB S12--Karolinska Instituet) could be done. Several variables such as clinical stage, pathology pattern and radiation response were also collected. The radiation responses were established clinically (by nasopharyngoscopy), by CT scanning and pathologically.
  
  
  RESULTS
  Sixty-five percent of our patients belong to the T3 and T4, whereby the N2-3 group consists 75% of them. Fourteen percent of the patients are Hsu type I, 48% are Hs type II and the rest belong to Hsu type III. Our study revealed that the mean SPF value was 14.62% (10.18%, which correlated (p < 0.05) with the tumor and nodal sizes. The rate of positive expression of the EBV-LMP1 was 50%, and did not show a correlation with the proliferation activity as well as the radiation response. However, it showed a significant correlation with the tumor and nodal size. There was a significant correlation between this proliferation value with the radiation response calculated by both, bivariate as well as by multivariate analysis. The complete and incomplete response group of patients has a SPF mean value of 10.1% +/- 9% and 17.1% +/- 9.3% respectively, with the SPF cut off value of 11%. There is no correlation between the proliferation rate with the histology pattern of NPC, as well as this radiation response with the histology pattern.
  
  
  CONCLUSIONS
  It is assumed that the expression of EBV-LMP1 prevents the apoptosis process through increasing the level of A20 protein, rather than inducing the expression of the EGFR in the proliferation pathway. SPF, one of the proliferation rate parameters, was the only factor that can be used as a radiation response predictor of NPC. It is assumed that the patients with high proliferation rate (SPF > 13%) should be irradiated in the unconventional irradiation scheme such as hyper-fractionated irradiation, or combined with another modality that will enhance the radiation effect, since the proliferation is too fast for once-a-day irradiation scheme. There were no correlations among pathology pattern, the proliferation rate and radiation response in NPC.
authors.affiliation: Dept. of Radiology, Faculty of Medicine, University of Indonesia, Jakarta.
authors.forename: S
authors.initials: S
authors.lastname: Gondhowiardjo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D002455:Cell Division / Q000502:physiology; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009303:Nasopharyngeal Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000532:radiotherapy*; D011237:Predictive Value of Tests; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins