title: Correlations between prognosis and regional biomarker profiles in head and neck squamous cell carcinomas.
abstract: Head and neck squamous cell carcinomas (HNSCC) show diverse clinicopathological features and are mostly linked with poor outcome. In this study, we tested if the expression of tumor growth, cell cycle and basement membrane anchorage related biomarkers allow prognostic and clinicopathological stratification of HNSCC. Archived HNSCC samples from 226 patients included into tissue microarrays (TMA) were tested using immunohistochemistry. Histopathological evaluation and the analysis of immunostaining for EGFR, Ki67, p53, p16(ink4) and Collagen XVII proteins were carried out in digital whole slides. Statistical evaluation was carried out using Pearson's Chi-square test and Kaplan-Meier survival analysis. In the tested cohort, hypopharyngeal cancers had the least favorable, and glottic cancers had the most favorable prognosis. High Ki67 positive tumor cell fractions were associated with significantly worse prognosis and elevated rate of lymph node metastasis. Both Ki67 and EGFR expression correlated significantly with the tumor localization. Ki67 index was the highest in the hypopharyngeal region and it proved to be the lowest in the glottic region. EGFR expression was the highest in the oral cavity and the lowest in the glottic region. The survival rate of patients with p16(ink4)-negative cancer was significantly lower than of those with p16(ink4)-positive disease. A significant inverse correlation was found between histological grade and the prognosis of HNSCC. Our data support that elevated Ki67 positive proliferating cell fractions contribute to the unfavorable prognosis of hypopharyngeal cancers, while glottic cancers have the most favorable prognosis because of the lowest Ki67 expression rate.
authors.affiliation: Department of Oto-Rhino-Laryngology, Jahn Ferenc South-Pest Hospital, 1st Köves Street, 1204, Budapest, Hungary, g.szentkuti@gmail.com.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Szentkúti
authors.forename: Kornél
authors.initials: K
authors.lastname: Dános
authors.forename: Diána
authors.initials: D
authors.lastname: Brauswetter
authors.forename: Gergő
authors.initials: G
authors.lastname: Kiszner
authors.forename: Tibor
authors.initials: T
authors.lastname: Krenács
authors.forename: László
authors.initials: L
authors.lastname: Csákó
authors.forename: Gábor
authors.initials: G
authors.lastname: Répássy
authors.forename: László
authors.initials: L
authors.lastname: Tamás
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D024041:Non-Fibrillar Collagens / Q000378:metabolism; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D066246:ErbB Receptors; D019394:Ki-67 Antigen; D024041:Non-Fibrillar Collagens; D016159:Tumor Suppressor Protein p53; D000097805:Collagen Type XVII; C495901:TP53 protein, human; C512478:EGFR protein, human