Immunoreactions for P53 isoforms are associated with ultrastructural proliferative profiles in benign thyroid nodules

P53 isoforms originate from the alternative initiation of P53 gene translation through usage of an internal promoter located in intron 4. All P53 isoforms are spliced in intron 9 and may modulate cell proliferation and cell fate outcome in response to DNA damage.

To examine immunoexpression of P53 isoforms in benign proliferative lesions occurring in multinodular thyroids and to assess the ultrastructural phenotype of P53 distribution in the thyrocytes of those lesions by electron microscopy.

By immunohistochemistry and transmission electron microscopy (TEM), we evaluated 38 multinodular thyroids containing a total of 102 benign lesions: 38 nodular goiters (NG; colloid=20, parenchymatous=18), 52 follicular adenomas (FA) and 12 Hashimoto's thyroditis (HT). FA were classified into 10 normo-follicular, 9 macro-follicular, 28 micro-follicular and 5 solid variants.

Immunoreaction for P53 isoforms was observed in approximately 50% of all lesions, except macrofollicular variant FA (33%). At TEM analysis, immunoreactive NG, FA and TH lesions showed signs of proliferation by simultaneous appearance of dispersed chromatin, increased amounts of cytoplasmic organelles and dilation of the rough endoplasmic reticulum. TEM signs of apoptosis and proliferation were also detected in FA, but with different rates compared to NG.

The immunohistochemical expression of P53 isoforms in NG, FA and HT suggests their role in the development of these lesions. Ultrastructural findings support the hypothesis that P53 immunoexpression correlates with reactive proliferative changes in thyrocytes.