title: Simultaneous over activation of EGFR, telomerase (h TERT), and cyclin D1 correlates with advanced disease in larynx squamous cell carcinoma: a tissue microarray analysis.
abstract: Overexpression of Epidermal Growth Factor Receptor (EGFR) and also of cell cycle control proteins, such as cyclin D1 is a frequent event in squamous cell carcinoma of the larynx (LSSC). Our aim was to correlate their protein levels with telomerase catalytic subunit (h-TERT) expression. Using tissue microarray technology, fifty-five paraffin embedded histologically confirmed primary LSSCs and also ten dysplastic lesions were cored at a diameter of 1.5 mm. Immunohistochemistry (IHC) was performed by the use of anti-EGFR, anti-cyclin D1, and anti-h TERT monoclonal antibodies. Chromogenic in situ hybridization (CISH) analysis was also applied using EGFR gene and chromosome 7 probes, respectively. EGFR, cyclin D1 and h-TERT protein overexpression was observed in 48/55 (87.2%), 19/55 (34.5%) and 21/55 (38.1%) carcinoma cases, respectively. EGFR protein expression was statistically associated with grade (P=0.01), and also with stage (P=0.001) of the examined tumors. Borderline statistical significance was assessed correlating overall cyclin D1 expression to h TERT expression (P=0.06). Simultaneous up regulation of the three proteins was established in 7/55 (12.7%) cases, correlated to the stage of the tumors (P=0.05). EGFR gene amplification was observed in 7/65 (10.7%) carcinomas and dysplasias, whereas chromosome 7 aneuploidy was detected in 4/65 (6.1%) of those cases.Simultaneous up regulation of EGFR, cyclin D1 and h TERT proteins correlates with advanced stage in LSCC. EGFR gene amplification and not only protein over expression maybe is the eligible criterion for targeted therapeutic strategies in those patients.
authors.affiliation: ENT Department, Hippokrateion Hospital, and Department of Histology & Embryology, Medical School, National and Kapodistrian University, Filotheis 37, N.Iraklio, Athens, Greece. achrysovergis@gmail.com
authors.forename: Aristeidis
authors.initials: A
authors.lastname: Chrysovergis
authors.forename: Vasilios G
authors.initials: VG
authors.lastname: Gorgoulis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Giotakis
authors.forename: Evangelos
authors.initials: E
authors.lastname: Tsiambas
authors.forename: Andreas
authors.initials: A
authors.lastname: Karameris
authors.forename: Christos
authors.initials: C
authors.lastname: Kittas
authors.forename: Aspasia
authors.initials: A
authors.lastname: Kyroudi
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D019938:Cyclin D1 / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019098:Telomerase / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D019938:Cyclin D1; C512478:EGFR protein, human; D066246:ErbB Receptors; D019098:Telomerase