PMID- 30553600 OWN - NLM STAT- MEDLINE DCOM- 20190621 LR - 20210208 IS - 1532-818X (Electronic) IS - 0196-0709 (Print) IS - 0196-0709 (Linking) VI - 40 IP - 2 DP - 2019 Mar-Apr TI - Molecular and immunologic analysis of laryngeal squamous cell carcinoma in smokers and non-smokers. PG - 213-217 LID - S0196-0709(18)30882-2 [pii] LID - 10.1016/j.amjoto.2018.11.009 [doi] AB - BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is strongly associated with tobacco use, but recent reports suggest an increasing incidence of LSCC in patients without traditional risk factors, suggesting an alternative etiology of tumorigenesis. The purpose of this study is to characterize this non-smoking population and to compare immunohistochemical markers in tumor specimens from non-smokers and smokers with LSCC. METHODS: A retrospective chart review of patients with LSCC at Johns Hopkins Hospital (JHH) was performed. A tissue microarray (TMA) was constructed with tumor specimen from non-smokers with stage and age-matched smokers and stained for a variety of immunologic and molecular targets. RESULTS: In the JHH cohort of 521 patients, 12% (n = 63) were non-smokers. Non-smokers were more likely to be <45 years old at time of diagnosis (OR 4.13, p = 0.001) and to have glottic tumors (OR 2.46, p = 0.003). The TMA was comprised of tumors from 34 patients (14 non-smokers, 20 smokers). Only 2 patients (6%) were human-papillomavirus (HPV) positive by high-risk RNA in situ hybridization (ISH). There was no correlation between smoking status and p16 (p = 0.36), HPV-ISH positivity (p = 0.79), phosphatase and tensin homolog (PTEN, p = 0.91), p53 (p = 0.14), or programmed death-ligand 1 (PD-L1, p = 0.27) expression. CONCLUSIONS: Non-smokers with LSCC are more likely to be younger at the time of diagnosis and have glottic tumors than smokers with LSCC. In TMA analysis of stage and age-matched specimens from smoker and non-smokers with LSCC, the pattern of expression for common molecular and immunologic markers is similar. Further, HPV does not appear to be a major causative etiology of LSCC in either smokers or non-smokers in our cohort of patients. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Malm, Ian-James AU - Malm IJ AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Hospital, Baltimore, MD, USA. Electronic address: imalm1@jhmi.edu. FAU - Rooper, Lisa M AU - Rooper LM AD - Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA. FAU - Bishop, Justin A AU - Bishop JA AD - Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA. FAU - Ozgursoy, Selmin Karatayli AU - Ozgursoy SK AD - Department of Otorhinolaryngology-Head and Neck Surgery, Ufuk University, Ankara, Turkey. FAU - Hillel, Alexander T AU - Hillel AT AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Hospital, Baltimore, MD, USA. FAU - Akst, Lee M AU - Akst LM AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Hospital, Baltimore, MD, USA. FAU - Best, Simon R AU - Best SR AD - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Hospital, Baltimore, MD, USA. LA - eng GR - K23 DC014758/DC/NIDCD NIH HHS/United States GR - L40 DC013350/DC/NIDCD NIH HHS/United States PT - Journal Article DEP - 20181122 PL - United States TA - Am J Otolaryngol JT - American journal of otolaryngology JID - 8000029 RN - 0 (Antigens, CD) RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - 0 (CDKN2A protein, human) RN - 0 (Cyclin-Dependent Kinase Inhibitor p16) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 0 (RNA, Viral) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) SB - IM MH - Age Factors MH - Aged MH - Antigens, CD MH - B7-H1 Antigen MH - Carcinoma, Squamous Cell/etiology/*genetics/*immunology/pathology MH - Cohort Studies MH - Cyclin-Dependent Kinase Inhibitor p16 MH - Female MH - Humans MH - Laryngeal Neoplasms/etiology/*genetics/*immunology/pathology MH - Male MH - Middle Aged MH - Neoplasm Staging MH - PTEN Phosphohydrolase MH - Papillomaviridae/genetics MH - Programmed Cell Death 1 Receptor MH - RNA, Viral MH - Retrospective Studies MH - *Smokers MH - Smoking/*adverse effects PMC - PMC6485418 MID - NIHMS1516576 OTO - NOTNLM OT - HPV OT - Immunohistochemistry OT - Laryngeal cancer OT - Squamous cell carcinoma COIS- No conflict of interest to disclose EDAT- 2018/12/17 06:00 MHDA- 2019/06/22 06:00 PMCR- 2020/03/01 CRDT- 2018/12/17 06:00 PHST- 2018/10/22 00:00 [received] PHST- 2018/11/05 00:00 [revised] PHST- 2018/11/20 00:00 [accepted] PHST- 2018/12/17 06:00 [pubmed] PHST- 2019/06/22 06:00 [medline] PHST- 2018/12/17 06:00 [entrez] PHST- 2020/03/01 00:00 [pmc-release] AID - S0196-0709(18)30882-2 [pii] AID - 10.1016/j.amjoto.2018.11.009 [doi] PST - ppublish SO - Am J Otolaryngol. 2019 Mar-Apr;40(2):213-217. doi: 10.1016/j.amjoto.2018.11.009. Epub 2018 Nov 22.