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


CONCLUSIONS
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.
Department of Otorhinolaryngology, Head and Neck Surgery, University of Cologne Medical Centre, Cologne, Germany.
Julia
J
Vent
Bastian
B
Haidle
Inga
I
Wedemeyer
Christian
C
Huebbers
Oliver
O
Siefer
Robert
R
Semrau
Simon F
SF
Preuss
Jens
J
Klussmann
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D059248:Chemoradiotherapy / Q000379:methods; D015331:Cohort Studies; D003131:Combined Modality Therapy; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000401:mortality / Q000556:secondary / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D037981:Neck Dissection; D009363:Neoplasm Proteins / Q000032:analysis*; D009382:Neoplasms, Unknown Primary / Q000737:chemistry* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D009959:Oropharyngeal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D066246:ErbB Receptors
carcinoma of unknown primary (CUP); identification of primary cancer; oropharynx; p16 / EGFR; prognosis