TP53 and C-MYC Co-Alterations – A Hallmark of Oral Cancer Progression / SIMULTANA ALTERACIJA TP53 I C-MYC GENA – OBELEŽJE PROGRESIJE ORALNIH KARCINOMA

Summary Background: Head and neck squamous cell carcinoma, including oral cancer, is the sixth most common cancer worldwide. Despite advances in surgery and treatment, the 5-year survival rate has not improved significantly. There- fore, reliable molecular markers for oral cancer progression are badly needed. Methods: We conducted a copy number analysis to esti- mate amplification status of c-myc, cycD1 and EGFR onco- genes, mutational PCR-SSCP analysis to determine activa- tion of H-ras oncogene and inactivation of TP55 tumour suppressor gene and methylation specific PCR analysis to evaluate hypermethylation of p16 and MGMT genes. Results: c-myc oncogene was amplified in 56.7%, cycD1 in 20% and EGFR in 16.7% of Oral Squamous Cell Carci- noma (OSCC) cases while H-ras was activated in 33.3% of samples. Amplification of c-myc was significantly associat- ed with the tumour grade 2. Interestingly, EGFR and H-ras alterations were mutually exclusive. p16 and MGMT were inactivated by hypermethylation in 30% and 13.3% of cases. Co-alteration of cycD1 and p16 were not observed in any of the analyzed samples. TP53 was inactivated in 56.7% of samples and was significantly associated with progression of OSCC, grade 2 and stage 2. Moreover, TP55 and c-myc oncogene were simultaneously altered in grade 2 OSCC. Conclusions: The most promising marker of OSCC pro- gression remains the TP53 tumour suppressor, which is the most frequently mutated gene in oral cancers. Since there is synergism between TP55 and c-myc, it seems that co- alteration of these two genes could be also a good marker of OSCC progression from gradel to grade 2 tumours.

Cell proliferation in lung fibrosis-associated hyperplastic lesions

1 Cell proliferative activity of atypical bronchioloalveolar epithelia in lung fibrosis cases treated with bleomycin (BLM) or radiation was investigated by studying the his tochemistry of the argyrophil nucleolar organiser regions (AgNORs) and proliferating cell nuclear antigen (PCNA). 2 Five and 14 autopsy cases of individuals who died of pulmonary fibrosis, caused by BLM treatment and irra diation respectively, were compared with (i) six control subjects who proved to have no apparent fibrosis of the lung at autopsy and (ii) four lung squamous cell carci noma cases. 3 Histopathologically, both the BLM-treated and irradiat ed cases showed extensive collapse of the lung caused by severe fibrosis, although proliferative epithelial lesions such as atypical bronchioloalveolar hyperplasia and squamous metaplasia were more prominent in the former. 4 The mean AgNOR numbers in both atypical hyper plasias and metaplasias, of either BLM or irradiation cases, were significantly higher than in control bronchi oloalveolar epithelial areas, whereas they were lower than in the lung cancers. Data for PCNA-labelling indices were in line with those for AgNORs. 5 The results indicate that atypical hyperplastic lesions in the bronchioloalveoli arising during the fibrosing process as induced by BLM, and by irradiation, are highly proliferative.