@article{c22c1cd5e5f34ca68f560426ceed6ac3,
title = "CD44 and associated markers in oral rinses and tissues from oral and oropharyngeal cancer patients",
abstract = "Objectives: Oral and oropharyngeal squamous cell carcinoma (OOPSCC) is a debilitating disease. Salivary rinses contain soluble tumor markers including CD44 (solCD44) and total protein (TP) that may aid detection and prognosis of these aggressive tumors. Here we aim to examine the relationship between these salivary biomarkers and tissue markers p16 and CD44 and determine whether these markers can predict progression-free survival (PFS) and overall survival (OS). Materials and methods: Prospective study to update biomarkers using oral rinses and tissues from OOPSC patients enrolled between 2007 and 2012 at an academic tertiary referral center. 64 cases from a 300-subject case-control study with archived tissue for immunohistochemistry were included. Results: 82.8% were male, 84.4% were ever smokers, 70.3% had disease stage T3-T4, and 57.8% presented with nodal disease. Nineteen patients (25%) were p16 positive. The group with strong tissue CD44 expression in membrane and cytoplasm had higher levels of solCD44 (mean 10.73 ng/ml) than other groups (5.47 ng/ml) (p = 0.033). TP levels were significantly reduced in oral rinses from subjects with p16 universal gross tumor tissue staining (mean 0.80 vs. 1.08 mg/ml; p = 0.039). On multivariate analysis, universal CD44 gross tissue staining and TP levels ≥ 1 mg/ml demonstrated poorer PFS, with the latter also affecting OS. Poorer survival was associated with soluble CD44 ≥ 5.33 ng/ml and TP ≥ 1 mg/ml. Conclusions: Direct associations were found between high solCD44 levels and strong membrane and cytoplasmic CD44 expression, and between high TP levels and peripheral/mixed p16 gross staining. Poorer PFS and OS are significantly associated with higher levels of solCD44 and protein in oral rinses.",
keywords = "CD44, Head and neck cancer, Human papillomavirus, Immunohistochemistry, Oral cancer, Oropharyngeal cancer, Prognostic factors, Salivary biomarkers, Survival, Total protein",
author = "Cohen, {Erin R.} and Reis, {Isildinha M.} and Carmen Gomez-Fernandez and Drew Smith and Lutecia Pereira and Freiser, {Monika E.} and Gia Marotta and Thomas, {Giovana R.} and Sargi, {Zoukaa B.} and Franzmann, {Elizabeth J.}",
note = "Funding Information: All of the authors listed have contributed sufficiently to the project to be included as authors, and no additional acknowledgements are relevant. This manuscript has not been previously published or is not under consideration for publication elsewhere. This publication is approved by all others and explicitly by the responsible authorities where the work was carried out. If accepted, this work will not be published elsewhere in the same form, in English or any other language, including electronically without written consent of the copyright-holder. Authors EC and EF had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. This work was supported by four grants that author EF received (NCI R01CA118584, NCI RO3 CA107828, 4BB-20 Bankhead-Coley, 10BG-02 Bankhead-Coley), Woman's Cancer Association, Vigilant Biosciences, Inc. Sylvester Comprehensive Cancer Center and University of Miami, Department of Otolaryngology. None of these grants influenced the design and conduct of the study, collection, management, analysis, and interpretation of the data, or the preparation, review, and decision to submit the manuscript for publication. Funding Information: This work was supported by four grants that author EF received (NCI R01CA118584, NCI RO3 CA107828, 4BB-20 Bankhead-Coley, 10BG-02 Bankhead-Coley), Woman{\textquoteright}s Cancer Association, Vigilant Biosciences, Inc., Sylvester Comprehensive Cancer Center and University of Miami , Department of Otolaryngology. None of these grants influenced the design and conduct of the study, collection, management, analysis, and interpretation of the data, or the preparation, review, and decision to submit the manuscript for publication. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",
year = "2020",
month = jul,
doi = "10.1016/j.oraloncology.2020.104720",
language = "English (US)",
volume = "106",
journal = "Oral Oncology",
issn = "1368-8375",
publisher = "Elsevier Limited",
}