p16 expression in carcinoma of unknown primary: diagnostic indicator and prognostic marker

Head Neck. 2013 Nov;35(11):1521-6. doi: 10.1002/hed.23190. Epub 2013 Jan 23.

Abstract

Background: Carcinoma of unknown primary (CUP) of the neck are heterogeneous tumors in their clinical and biological characteristics, and a preoperative prognostic marker is desirable to optimize staging and therapy and to improve outcome and survival. For CUP syndrome, no optimized diagnostic and treatment strategy or biomarker have yet been determined.

Methods: Forty-seven patients presenting with CUP syndrome were analyzed after thorough standard diagnostic staging procedures. All patients were surgically treated with tonsillectomy, neck dissection of the diseased neck, as well as adjuvant chemoradiation. The tissue of lymph node metastases (and, if found, of the primary tumor) was analyzed regarding expression of p16, epidermal growth factor receptor (EGFR), and presence of human papillomavirus (HPV) DNA.

Results: In 39% of all cases (20 of 47), the primary cancer was found during diagnostic workup. If HPV DNA was detected in the neck lymph node metastasis, the primary cancer was significantly more frequently found in the oropharynx (p = .002). Patients with a p16-positive tumor had a significantly higher 5-year overall survival (OS; 33% vs 69%; p = .045, disease-free survival [DSF] 77% vs 89%; p = not significant [NS]). Patients with p16-positive neck metastasis and no detectable primary cancer had a better prognosis. Expression of EGFR in this series did not have a significant effect on prognosis.

Conclusion: In patients presenting with CUP syndrome, p16 immunohistochemistry can serve to locate the primary cancer in the oropharynx. It is a positive prognostic indicator in patients with those heterogeneous cancers.

Keywords: carcinoma of unknown primary (CUP); identification of primary cancer; oropharynx; p16 / EGFR; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Biopsy, Needle
  • Chemoradiotherapy / methods
  • Cohort Studies
  • Combined Modality Therapy
  • Cyclin-Dependent Kinase Inhibitor p16
  • Disease-Free Survival
  • ErbB Receptors / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Head and Neck Neoplasms / chemistry
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / secondary
  • Head and Neck Neoplasms / therapy
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neck Dissection
  • Neoplasm Proteins / analysis*
  • Neoplasms, Unknown Primary / chemistry*
  • Neoplasms, Unknown Primary / mortality
  • Neoplasms, Unknown Primary / pathology*
  • Neoplasms, Unknown Primary / therapy
  • Oropharyngeal Neoplasms / chemistry*
  • Oropharyngeal Neoplasms / mortality
  • Oropharyngeal Neoplasms / secondary*
  • Oropharyngeal Neoplasms / therapy
  • Prognosis
  • Retrospective Studies
  • Risk Assessment
  • Statistics, Nonparametric
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins
  • ErbB Receptors