Reflections

  Significance Overview   RET/PTCs are a group of oncogenic fusion proteins derived from the proto-oncogene c-RET, structurally related to a family of receptor tyrosine kinases (1-3). RET/PTCs result from joining the carboxy-terminus of fusion partners with the amino-terminus of c-RET, leading to constitutively active kinase. Of the 11 different fusion genes reported, RET/PTC1 or RP1 and RET/PTC3 or RP3 are the most prevalent (1). In the case of RP3, the amino terminus is derived from the androgen receptor-associated protein, ARA-70 (Fig. 1) (4). RP3 drives three different pathways that strongly influence biological properties of the tumor. First, the constitutively active c-terminal RET kinase domain activates RAS/BRAF/MEK/ERK, PI3K/AKT, p38MAPK, and JNK pathways leading to thyrocyte transformation (5). Second, kinase activity leads to precocious phosphorylation of RP3 itself and other intracellular proteins that provide tumor-specific targets for the adaptive immu...

If you read about thyroid cancer, everyone agrees that its incidence is on the rise. In recent months, there has been lots of press coverage as how this increased thyroid incidence is due to overdiagnosis. To illustrate the overdiagnosis with an example, we need to take a look at South Korea. There was a huge increase in the incidence of thyroid cancer in South Korea which was blamed on overdiagnosis . But a recent review article on this topic cautions; not so fast . Thyroid cancers form about 2.1% of total cancer diagnoses worldwide, with women disproportionately affected, accounting for about 77% of the cases. The phenomenon of more women patients than men is unique to thyroid pathology and is also seen in Hashimoto's thyroiditis and Graves' disease. Majority of thyroid cancers are termed differentiated with two main subtypes, papillary thyroid cancers (PTC) and follicular thyroid cancers (FTC). The increased incidence of the thyroid cancer is mainly attributed to increas...

BACKGROUND                                                Sclerosing mucoepidermoid carcinoma with eosinophils of thyroid (SCEME) is a rare thyroid carcinoma. Although it is believed to take a slow, indolent approach to grow, the carcinoma can cause complications due to involvement of large part of the thyroid and neck. Apart from the involvement of thyroid gland, SCEME is also known to metastasize to different body parts, further complicating the prognostic outcome. The interesting part of the clinical picture is sclerosis and fibrosis of the involved part of the thyroid gland, and Hashimoto’s Thyroiditis (HT) in non-involved portion of the thyroid. The stroma shows infiltration of eosinophils, lymphocytes and plasma cells. SCEME has been found to be...

Follicular Thyroid cancer and new driver mutations New developments on thyroid cancer front this week. A research group from South Korea  published an article on the transcriptional and mutational landscape of follicular (FTC) and papillary thyroid cancers (PTC). The reason this is big news is that this is the first time when a comprehensive data is being published on FTCs. Comprehensive data on PTC already exist as it was published in 2014 . I am not going to discuss the whole of the article but there was few interesting points which caught the eye. One of which was that the authors proposed new driver mutations for thyroid cancer, of the many two of them are EZH1 (a member of polycomb group protein complex) and LKB1. The interesting part came from another group in Italy who published a paper in JCI  about role of EZH1 in development of thyroid adenomas. The paper describes the role of cAMP signaling from TSHR mutations which when combined with EHZ1 mutations lead t...