Expression and Significance of Cytokeratin 7, a Squamocolumnar Junction Marker, in Head and Neck Squamous Cell Carcinoma
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ORIGINAL PAPER
Expression and Significance of Cytokeratin 7, a Squamocolumnar Junction Marker, in Head and Neck Squamous Cell Carcinoma Mitra Mehrad1 · William D. Dupont2 · W. Dale Plummer Jr2 · James S. Lewis Jr1,3 Received: 26 October 2017 / Accepted: 6 December 2017 © Springer Science+Business Media, LLC, part of Springer Nature 2017
Abstract The favorable features of high-risk human papillomavirus (HPV) in the head and neck are limited to those harboring transcriptionally-active HPV, which occur predominantly in the oropharynx (OP). Factors rendering the OP susceptible to HPV oncogenesis are largely unexplored. The role of cytokeratin 7 (CK7) in predisposition to HPV and cancer in the cervix has been evaluated. However, its significance in the H&N is unknown. CK7 immunohistochemistry was performed on a tissue microarray cohort of OP and non-oropharyngeal (NOP) squamous cell carcinomas (SCC) with known clinical follow-up and HPV E6/7 mRNA status. Expression was graded based on the distribution (1 ≤ 33%, 2 = 33–66%, 3 ≥ 66%) and intensity (1 = weak, 2 = strong) with combined score of ≥ 2 considered positive. Survival analysis was performed. Seventy-four NOPSCCs and 204 OPSCCs were studied. HPV was positive in 2.7% of NOPSCCs and 70.9% of OPSCCs. CK7 was positive in 23.0% of OPSCCs and 14.8% of NOPSCCs (p = 0.2), and in 24.1% of HPV positive versus 17.2% of negative patients (p = 0.2). There was no correlation with age, race, gender, HPV status, histologic type, tumor subsite, treatment, stage, or co-morbidities, and CK7 expression was not significantly associated with overall or disease specific survival. In our series, CK7 is positive in ~ 25% of H&N SCCs, although usually only focally. While CK7 has been suspected to be overexpressed selectively in HPV-related OPSCCs due to their origination from tonsillar crypt epithelium, we did not find any significant difference by anatomic H&N subsite, nor by HPV status, for its expression and found no association with patient survival. Keywords Oropharynx · Human papillomavirus · Cytokeratin 7 · Squamous cell carcinoma · Head and neck · Tonsillar crypt epithelium
Introduction Oropharyngeal squamous cell carcinoma (OPSCC) is now recognized as a distinct entity among the head and neck squamous cell carcinomas due to its frequent association with high-risk human papillomavirus (HPV). Studies have shown that HPV-positive OPSCC patients are generally younger and less frequently use alcohol and tobacco * Mitra Mehrad [email protected] 1
Vanderbilt University Medical Center, Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, C‑3321A Medical Center North, Nashville, TN 37232, USA
2
Vanderbilt University Medical Center, Biostatistics, Nashville, TN, USA
3
Vanderbilt University Medical Center, Otolaryngology, Nashville, TN, USA
compared to those with HPV-negative SCC [1–4]. At the molecular level, HPV-positive SCCs less often harbor p53 mutations compared with HPV-negative SCCs [5], and they almost always overexpress p1
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