Thyroid cancer and the immune system: a model for effective immune surveillance.

Differentiated thyroid cancers, including papillary and follicular variants, are a useful model with which to examine interactions between cancer and the immune system. Differentiated thyroid cancers are detected in only 20,000 individuals annually in the USA, but thyroid microcarcinomas (< 1 cm in diameter) are far more common. This suggests that the immune system might restrain the growth of these microcarcinomas. On the clinical level, patients with lymphocytes that infiltrate into papillary thyroid cancer have improved survival, supporting the notion that immune system activation might improve this. Together, these observations suggest that the growth and distant spread of thyroid carcinoma are suppressed by mechanisms of immune surveillance, possibly involving lymphocytes, macrophages and their secreted products. In this review, we examine the general hypothesis of immune surveillance and the data pertaining to the roles of lymphocytes, dendritic cells and cytokines in the immune response against thyroid cancers.

Cytoplasmic localization of the paired box gene, Pax-8, is found in pediatric thyroid cancer and may be associated with a greater risk of recurrence.

The paired box-8 protein (Pax-8) has been observed in the nucleus of normal adult thyroids, follicular adenomas, follicular thyroid cancers, and papillary thyroid cancers (PTC) but not undifferentiated thyroid cancers. To our knowledge, Pax-8 has not been studied in pediatric thyroid cancer. Because of the more favorable prognosis for PTC in children compared to young patients, we hypothesized that Pax-8 expression might be different in pediatric thyroid cancers. To test this, we stained 47 thyroid lesions from children and young patients for Pax-8. Pax-8 was located in the cytoplasm (cPAX) or nucleus (nPAX) in the majority of samples. There was no significant difference in nPAX between benign and malignant lesions. However, cPAX was more commonly seen in PTC than autoimmune diseases (p = 0.01) and the intensity of cPAX staining correlated with tumor size (p = 0.041), metastasis, age, completeness of resection, local invasion, and tumor size (MACIS) scores (p = 0.045), and the presence of invasion, metastasis, recurrence, or persistence (p = 0.012). Disease-free survival was significantly reduced for cancers with intense cPAX staining (p = 0.0003). These data show that cPAX is common in PTC, and although limited by small sample size, suggest an association with higher MACIS scores, an aggressive clinical course, and an increased risk of clinically evident recurrence for children and young patients.