Prognostic significance of p16 expression in advanced cervical cancer treated with definitive radiotherapy.

Abstract

PURPOSE:

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.

MATERIALS AND 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).

CONCLUSION:

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: Julie K Schwarz, James S Lewis Jr, John Pfeifer, Phyllis Huettner, Perry Grigsby
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 84 Issue 1 Pg. 153-7 (Sep 01 2012) ISSN: 1879-355X [Electronic] United States
• PMID: 22330994 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• CDKN2A protein, human
• Cyclin-Dependent Kinase Inhibitor p16
• Neoplasm Proteins
• Radiation-Sensitizing Agents
• Cisplatin

Topics

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Cisplatin (therapeutic use)
• Cyclin-Dependent Kinase Inhibitor p16
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Immunohistochemistry
• Middle Aged
• Neoplasm Proteins (metabolism)
• Prognosis
• Radiation-Sensitizing Agents (therapeutic use)
• Retrospective Studies
• Tissue Array Analysis
• Uterine Cervical Neoplasms (metabolism, mortality, pathology, radiotherapy)