Clinical and pathological implications of concurrent autoimmune thyroid disorders and papillary thyroid cancer

Abstract

Cooccurrences of chronic lymphocytic thyroiditis (CLT) and thyroid cancer (DTC) have been repeatedly reported. Both CLT and DTC, mainly papillary thyroid carcinoma (PTC), share some epidemiological and molecular features. In fact, thyroid lymphocytic inflammatory reaction has been observed in association with PTC at variable frequency, although the precise relationship between the two diseases is still debated. It also remains a matter of debate whether the association with a CLT or even an autoimmune disorder could influence the prognosis of PTC. A better understanding about clinical implications of autoimmunity in concurrent thyroid cancer could raise new insights of thyroid cancer immunotherapy. In addition, elucidating the molecular mechanisms involved in autoimmune disease and concurrent cancer allowed us to identify new therapeutic strategies against thyroid cancer. The objective of this article was to review recent literature on the association of these disorders and its potential significance.

Figure 1

Activation of a self-specific T-cell initiates a cascade of events that amplifies the immune response and involves both CD4 and CD8 T cells, inducing an antibody-mediated response. B: B cells; IFN-γ: interferon-γ; IL-2: interleukin-2; MHCII: major histocompatibility class II; T: T cells; Tc: cytotoxic T-cell; Th: T helper cell (adapted from [51]).

Figure 2

Multistep carcinogenesis model of thyroid cancer formation. Formation of benign thyroid tumors occurs as a result of alteration of various growth factors. Follicular neoplasms are formed from thyrocytes by mutations of RAS and other factors, as shown in the figure. Papillary cancers are formed by alterations in RET/PTC and other oncogenes. Undifferentiated tumors are formed from differentiated tumors by mutations of tumor suppressor genes (adapted from [87]).

Figure 3

Putative links between RET/PTC rearrangement and concurrent thyroid inflammation. (a) RET/PTC could drive expression of several proinflammatory molecules that may elicit concurrent inflammation. Another possibility (b) is inflammation propitiating RET/PTC rearrangement. Inflammation produces reactive oxygen species and free radicals that may facilitate DNA damage and chromosomal abnormities, like RET/PTC rearrangement. (c) Molecules released by inflammation could sustain the survival of thyroid cells in which RET/PTC rearrangements randomly occur, thereby allowing the selection of clones that acquire additional genetic lesions and thus become resistant to oncogene-induced apoptosis.