title: P16(INK⁴a) overexpression is associated with CDKN2A mutation and worse prognosis in HPV-negative laryngeal squamous cell carcinomas.
abstract: We studied the expression of p16(INK4a) in a series of HPV-negative laryngeal squamous cell carcinomas and assessed its association with prognosis. Forty-five patients with laryngeal carcinoma were included in the study. Clinicopathological features and prognosis were reviewed. p16(INK4a) protein expression was analysed through immunohistochemistry. We analysed messenger RNA (mRNA) in 25 cases through quantitative reverse transcription polymerase chain reaction. HPV status was assessed by PCR using three different protocols based on MY09/11 and GP5/6 primers. Four out of 45 (9 %) cases overexpressed p16(INK4a) protein and showed a tendency to worse survival that was significant for stages I-III (log-rank p value = 0.001). Expression of p16(INK4a) mRNA was high in 12 out of 25 (48 %) cases using an arbitrary cut-off level. All tumours were HPV negative with all three detection methods. A CDKN2A mutation was found in eight cases. One case with a missense and one with a frameshift mutation showed p16(INK4a) protein expression by immunohistochemistry. Six out of seven (86 %) mutated but only 6 out of 18 (33 %) non-mutated cases presented p16(INK4a) mRNA overexpression (p = 0.03). Our findings suggest that p16(INK4a) overexpression, both at protein and mRNA levels, may reflect CDKN2A genetic alterations in HPV-negative laryngeal squamous cell carcinomas.
authors: Department of Pathology, Hospital Clínic, Villarroel, 170, 08036, Barcelona, Spain.
authors: Ana B
authors: AB
authors: Larque
authors: Laura
authors: L
authors: Conde
authors: Sofia
authors: S
authors: Hakim
authors: Llucia
authors: L
authors: Alos
authors: Pedro
authors: P
authors: Jares
authors: Isabel
authors: I
authors: Vilaseca
authors: Antonio
authors: A
authors: Cardesa
authors: Alfons
authors: A
authors: Nadal
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D030361:Papillomavirus Infections; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16
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