FGFR3 and PIK3CA mutations were more frequent in low-grade noninvasive papillary carcinomas compared with high-grade noninvasive papillary carcinomas and carcinomas in situ (p < 0.0001), while the opposite was true for TP53 (p < 0.0001).
In urothelial cancers, TP53 is typically inactivated by mutations in one allele and loss of the wildtype allele and more frequently in invasive compared to papillary carcinomas.
RET expression is highly prevalent in local papillary carcinoma, indicating a significant role in the pathogenesis of this tumour, with no apparent role in tumour behaviour and survival outcome. p53 on the other hand appears to be a significant factor in the latter events.
While over-expression of p53 protein was not significantly related to that of MDM2 and Bcl-2 proteins, over-expression of MDM2 and Bcl-2 in papillary carcinoma were associated.
These data demonstrate that as opposed to the few reports on tumors arising after therapeutic external irradiation, ras mutations are not primary events in the development of post-Chernobyl thyroid papillary carcinomas. p53 mutations do not appear to be important in the development of these tumors, but may in some cases have a role in progression to a more aggressive phenotype that has not yet fully manifested in these pediatric neoplasms.
Considering the two methods together, p53 damages were observed in two out of 11 papillary carcinomas without metastasis (18.1%), one out of nine papillary carcinomas with metastasis (11.1%), two out of 14 follicular carcinomas without metastasis (14.2%), and five out of 11 follicular carcinomas with metastasis (45.4%).
We conclude that somatic p53 mutations are very frequent in serous papillary carcinomas, particularly in tumors of high grade, bilaterality, and peritoneal spread, less frequent in other carcinoma types and extremely rare in borderline and benign tumors of the ovary.
The distribution of p53 mutations was significantly different (P = 0.006) in the histotypes examined: mutations were frequent in medullary (39%) and ductal (26%), less common in lobular (12%), and absent in mucinous and papillary carcinomas.
The fact that no mutations were detected in coexisting foci of papillary carcinomas from the same patients shows that these mutations of the p53 gene occurred after development of papillary carcinomas.