Immunological aspects of papillary thyroid carcinoma

Sammanfattning: Papillary thyroid carcinoma (PTC) is a puzzling disease. Although approximately 70% of patients with PTC have regional lymph node metastases at initial surgery, the long term survival is over 95%. A hallmark of the disease is an avid, T-cell dominated inflammatory reaction, which for over half a century has stimulated hypotheses of a tumor-specific immune response. We have investigated this possibility by examining indicators of humoral immunity, including immunoglobulin G (IgG) and complement by immunohistochemistry. Over 80% of PTC tumors were found to demonstrate significant deposits of both IgG and complement factors, indicating complete activation of the complement cascade. The main complement regulatory proteins CD55 and CD59, which normally inhibit complement deposition at the cell surface, were present in PTC tumor cells as well as normal thyrocytes. This suggests that complement regulation is circumvented by some other mechanism in PTC.Having demonstated tumor-specific antibody deposits in PTC, we sought the atigens against which these antibodies were raised. Using immunoprecipitation and Western blot with serum from PTC patients as the antibody source, a 35 kDa protein was isolated from a PTC tumor, and peptide sequencing identified it as a fragment of cytokeratin 1. This 68 kDa intermediate filament protein is normally expressed only in the upper levels of the epidermis. Further investigations revealed the full length cytokeratin 1 protein in PTC tissues by immunohistochemistry, immunoprecipitation and Western blot using a monoclonal antibody specific for cytokeratin 1. Antibodies isolated directly from PTC tissue were also found to have bound cytokeratin 1 in situ.As the etiology and behavoir of PTC have been closely tied to the RET/PTC oncogene, which has also been demonstrated in autoimmune thyroiditis, we examined the presence of the RET protein in PTC by immunohistochemistry. 86% of the PTC tumors demonstrated cytoplasmic staining for RET, suggestive of RET/PTC activation, particularly in areas of intense inflammation, The results suggest that RET/PTC expression may be involved in the immunogenic response to PTC.

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