title: Nuclear survivin is associated with cell proliferative advantage in uterine cervical carcinomas during radiation therapy.
abstract: BACKGROUND
  Although the anticancer effects of radiation therapy for patients with uterine cervical squamous cell carcinoma (U-SCC) are widely acknowledged, little is known about the resultant morphological alterations in tumour tissue kinetics.
  
  
  OBJECTIVE
  To make a detailed assessment of possible roles of survivin expression in apoptosis and cell proliferation in U-SCC during radiation therapy.
  
  
  METHODS
  181 biopsy specimens from 55 consecutive U-SCCs of patients receiving radiation therapy were studied using a combined morphological (apoptosis) and immunohistochemical (MIB-1 and survivin) approach. The intracellular distribution of various splice variants of the survivin gene was also examined.
  
  
  RESULTS
  Tumour cell proliferation, determined as MIB-1 labelling indices (LIs), as well as nuclear survivin (N-Surv) LIs, were inversely correlated with irradiation dosage, in contrast to relatively minor changes in apoptotic indices, suggesting a shift in tumour tissue kinetics towards a relative predominance of cell deletion. In addition, the low N-Sur LI category showed significant stepwise decrease in MIB-1 LIs during therapy, in contrast to no changes in the high category. Exogenous overexpression of three variants of the survivin gene resulted in different expression patterns, showing cytoplasmic staining with or without dot formation for survivin and survivin-2B and distinct nuclear accumulation for survivin-deled exon 3 (Ex3).
  
  
  CONCLUSIONS
  Results showed that nuclear survivin, including survivin itself and the survivin-Ex3 splice variants, may participate in modulation of altered cell kinetics of U-SCC during radiation therapy.
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Pattama
authors.initials: P
authors.lastname: Chaopotong
authors.forename: Sabine
authors.initials: S
authors.lastname: Kajita
authors.forename: Miki
authors.initials: M
authors.lastname: Hashimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Saegusa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing / Q000528:radiation effects; D017209:Apoptosis / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008875:Middle Aged; D020033:Protein Isoforms / Q000378:metabolism; D000077022:Survivin; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D051034:Inhibitor of Apoptosis Proteins; D020033:Protein Isoforms; D000077022:Survivin; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases