title: Prognostic significance of p16 expression in advanced cervical cancer treated with definitive radiotherapy.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the prognostic significance of p16 immunohistochemistry (IHC) in patients with advanced cervical cancer treated with radiation therapy.
  
  
  METHODS
  This was a retrospective study of 126 patients with International Federation of Gynecology and Obstetrics Stages Ib1-IVb cervical cancer treated with radiation. Concurrent cisplatin chemotherapy was given to 108 patients. A tissue microarray (TMA) was constructed from the paraffin-embedded diagnostic biopsy specimens. Immunoperoxidase staining was performed on the TMA and a p16 monoclonal antibody was utilized. IHC p16 extent was evaluated and scored in quartiles: 0 = no staining, 1 = 1-25% of cells staining, 2 = 26 to 50%, 3 = 51 to 75%, and 4 = 76 to 100%.
  
  
  RESULTS
  The p16 IHC score was 4 in 115 cases, 3 in 1, 2 in 3 and 0 in 7. There was no relationship between p16 score and tumor histology. Patients with p16-negative tumors were older (mean age at diagnosis 65 vs. 52 years for p16-positive tumors; p = 0.01). The 5-year cause-specific survivals were 33% for p16-negative cases (score = 0) compared with 63% for p16-positive cases (scores 1, 2, 3 or 4; p = 0.07). The 5-year recurrence-free survivals were 34% for those who were p16-negative vs. 57% for those who were p16-positive (p = 0.09). In addition, patients with p16-positive tumors (score > 0) were more likely to be complete metabolic responders as assessed by the 3-month posttherapy 18 [F]-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomograph compared with patients with p16-negative tumors (p = 0.03).
  
  
  CONCLUSIONS
  p16 expression is predictive of improved survival outcome after chemoradiation therapy for advanced-stage invasive cervical carcinoma. Further testing will be needed to evaluate p16-negative cervical tumors.
authors.affiliation: Department of Radiation Oncology, Mallinckrodt Institute of Radiology, 4921 Parkview Place, St. Louis, MO 63110, USA. jschwarz@radonc.wustl.edu
authors.forename: Julie K
authors.initials: JK
authors.lastname: Schwarz
authors.forename: James S
authors.initials: JS
authors.lastname: Lewis
authors.forename: John
authors.initials: J
authors.lastname: Pfeifer
authors.forename: Phyllis
authors.initials: P
authors.lastname: Huettner
authors.forename: Perry
authors.initials: P
authors.lastname: Grigsby
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002945:Cisplatin / Q000627:therapeutic use; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin