p53 overexpression and thymoma prognosis

Aim: Ninety primary thymomas were retrospectively investigated to assess whether the overexpression of the p53 protein could offer additional prognostic information. Materials and Methods: 90 patients (mean age: 49 years; 50 females and 40 males; 55 with myastenia gravis) were included in the study. According to the European classification, 11 were medullary (MT), 53 mixed cortico-medullary (MixT), 7 predominantly cortical (PCT) and 19 cortical (CT) thymomas. According to the American scheme, 11 were spindle cell (S), 35 predominantly lymphocytic (PL), 22 mixed lympho-epithelial (MLE) and 22 predominantly epithelial (PE) thymomas. 46 were Masaoka's stage I, 19 stage II, 13 stage III and 12 stage IVa. The mean follow-up period was 72 months (1-161). Paraffin-embedded sections were stained with the monoclonal antibody DO7 using the LSAB method. Cases with more than 10% positive nuclei were considered positive. Serial sections were stained with the argyrophilic method of Ploton for the detection of the Nucleolar Organizer Regions (AgNORs). DNA flow cytometry was performed on paraffin embedded tissues using a FACScan flow cytometer. Chi-square test, ANOVA, uni- and multivariate survival analysis were used for statistics. Results: p53 overexpression was found in 48 cases (53.4%). It was higher in PE (58%) than in S (36%) and PL (48%) subtypes; in PCT (71%) and CT (68%) than in MT (36%); in stage III (61%) and IVa (67%) than in stages I (46%) or II (58%); in invasive (61%) than in non-invasive (46%) cases, and in DNA aneuploid (71%) than diploid (49%) cases. However, the differences were not significant. By contrast, p53 positive thymomas had a significantly higher AgNOR counts (6.34) than negative cases (5.36; p=0.01). In the univariate analysis, the 10 year survival rates were 83% for p53 negative vs. 52% for p53 positive cases (p=0.01). Histological subtypes of the American classification (p=0.006), tumour stage (p<0.0001), invasion (p=0.0001), DNA content (p=0.005) and AgNOR counts (p<0.0001) were also strongly correlated with survival. In the multivariate analysis, only tumour stage (p<0.001) and AgNOR counts (p=0.009) retained independent prognostic significance. Conclusion: p53 overexpression is an additional prognostic variable in thymoma The correlation between p53 overexpression and cell proliferative activity suggests that p53 overexpression may be due to the accumulation of a mutated protein. Finally, stage and proliferative activity are to be regarded as the most important prognostic factors in thymoma.