Multiple genetic lesions in laryngeal squamous cell carcinomas

• Published in: Cancer 1995-03, Vol.75 (6), p.1292-1301
• Main Authors: Fracchiolla, Nicola S., Pignataro, Lorenzo, Capaccio, Pasquale, Trecca, Dino, Boletini, Alketa, Ottaviani, Antonio, Polli, Elio, Maiolo, Anna T., Neri, Antonino
• Format: Article
• Language: English
• Subjects: Aged; and N‐ras; Base Sequence; bcl‐1; Biological and medical sciences; Blotting, Southern; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Cyclin D1; c‐erbB‐1; c‐myc; DNA Mutational Analysis; DNA, Neoplasm - analysis; Fibroblast Growth Factor 3; Fibroblast Growth Factors - genetics; Genes, erbB - genetics; Genes, myc - genetics; Genes, p53 - genetics; Genes, ras - genetics; Humans; H‐ras; Int‐2; K‐ras; Laryngeal Neoplasms - genetics; Laryngeal Neoplasms - pathology; laryngeal squamous cell carcinomas; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Otorhinolaryngology. Stomatology; p53; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Proto-Oncogene Proteins - genetics; Proto-Oncogenes - genetics; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/1097-0142(19950315)75:6<1292::AID-CNCR2820750611>3.0.CO;2-B

Background. To understand the molecular pathogenesis of laryngeal squamous cell carcinomas (LSCCs), this study investigated the involvement of various protooncogene loci (bcl‐1, int‐2, c‐erbB‐1, c‐myc, ras) and the p53 tumor suppressor gene in 18 patients with LSCC (15 at clinical presentation, 3 in clinical relapse). Methods. For all patients, the mutations affecting the p53 and the H‐, K‐, and N‐ras genes were evaluated by polymerase chain reaction (PCR), single‐strand conformation polymorphism, and the direct sequencing of PCR‐amplified fragments. The bcl‐1, int‐2, c‐erbB‐1, and c‐myc loci of 15 patients were investigated using Southern blot analysis. Results. A mutation of the p53 gene was detected in 5/18 patients (≈28%), bcl‐1 locus amplification in 4/15 (≈26%), c‐erbB‐1 locus amplification in 2/15 (≈13%), and c‐myc locus amplification in 1/15 (≈6%). The simultaneous presence of more than one genetic lesion was observed in four patients; two showed int‐2/bcl‐1 coamplification, and two int‐2/c‐erbB‐1 coamplification, one of whom also showed a p53 gene mutation. A novel p53 mutation involving the splice acceptor site of exon 6 was detected in one patient. Two of the five patients positive for p53 mutations had clinical relapses of primary tumors. bcl‐1 locus amplification only was observed in patients with lymph node metastases (4/6). All but one of the patients with molecular genetic lesions showed a peculiar infiltrating pattern. Conclusions. Overall, these results show that alterations of known protooncogenes and the p53 tumor suppressor gene are involved in a large proportion of LSCCs (11/18; ≈60%) and may suggest that distinct molecular pathways occur in the pathogenesis of these tumors. Cancer 1995;75:1292‐1301.