title: Prognostics of Cyclin-D1 expression with chemoradiation response in patients of locally advanced oral squamous cell carcinoma.
abstract: OBJECTIVE
  Cyclin-D1 has been strongly implicated in cell cycle proliferation particularly in the G1/S checkpoint in the cell cycle, and prognosis in many human malignancies. The present study evaluates its prognostic significance with chemoradiation response in patients of locally advanced oral squamous cell carcinoma (OSCC).
  
  
  METHODS
  A total of 97 OSCC patients (females = 19 and males = 78), aged 20-67 years and stage III/IV were recruited. Treatment response was assessed according to World Health Organization criteria. Cyclin-D1 expression in tumor tissue was estimated by immunohistochemical method and quantified as percentage positive nuclei.
  
  
  RESULTS
  The Cyclin-D1 expression showed significant (P < 0.01 or P < 0.001) association with tumor size, lymph node status, and clinical stage. After chemoradiation, there were 53.6% complete response (CR) and 34.0% partial response (PR) in primary tumor, and 49.5% CR and 39.2% PR in lymph node; giving an overall response rate of 85.6%. Further, the mean Cyclin-D1 expression showed significant (P < 0.05 or P < 0.001) and inverse association with chemoradiation responses (tumor size, lymph node status and overall treatment response). The 2-year progression-free and overall survival (OS) was 95.89% and 83.31% respectively. Multivariate Cox regression analysis found site of primary tumor, clinical stage, and Cyclin-D1 expression the significant (P < 0.05 or P < 0.01) and independent prognostic markers of OS and among these Cyclin-D1 expression showed the worst prognosis. The high Cyclin-D1 expression (>50%) also showed significantly lower survival in OSCC patients when compared with those had low (<10%) and moderate expressions (10-50%) (Logrank test: χ(2) = 44.42, P < 0.001).
  
  
  CONCLUSIONS
  The high Cyclin-D1 expression may serve as a poor prognostic marker in OSCC.
authors.forename: Huma
authors.initials: H
authors.lastname: Khan
authors.affiliation: Department of Radiotherapy, C.S.M. Medical University, Lucknow, Uttar Pradesh, India.
authors.forename: Seema
authors.initials: S
authors.lastname: Gupta
authors.forename: Nuzhat
authors.initials: N
authors.lastname: Husain
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Misra
authors.forename: Navin
authors.initials: N
authors.lastname: Singh
authors.forename: M P S
authors.initials: MP
authors.lastname: Negi
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D059248:Chemoradiotherapy; D019938:Cyclin D1 / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D019938:Cyclin D1