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Front Endocrinol (Lausanne). 2012 Feb 27;3:33. doi: 10.3389/fendo.2012.00033. eCollection 2012.

Clinical outcome, role of BRAF(V600E), and molecular pathways in papillary thyroid microcarcinoma: is it an indolent cancer or an early stage of papillary thyroid cancer?

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Division of Cancer Biology and Angiogenesis, Harvard Medical School, Beth Israel Deaconess Medical Center Boston, MA, USA.


Most human thyroid cancers are differentiated papillary carcinomas (PTC). Papillary thyroid microcarcinomas (PTMC) are tumors that measure 1 cm or less. This class of small tumors has proven to be a very common clinical entity in endocrine diseases. PTMC may be present in 30-40% of human autopsies and is often identified incidentally in a thyroid removed for benign clinical nodules. Although PTMC usually has an excellent long-term prognosis, it can metastasize to neck lymph nodes; however deaths related to this type of thyroid tumor are very rare. Few data exist on molecular pathways that play a role in PTMC development; however, two molecules have been shown to be associated with aggressive PTMC. S100A4 (calcium-binding protein), which plays a role in angiogenesis, extracellular matrix remodeling, and tumor microenvironment, is over-expressed in metastatic PTMC. In addition, the BRAF(V600E) mutation, the most common genetic alteration in PTC, is present in many PTMC with extra thyroidal extension and lymph node metastasis. Importantly, recently developed selective [e.g., PLX4720, PLX4032 (Vemurafenib, also called RG7204)] or non-selective (e.g., Sorafenib) inhibitors of BRAF(V600E) may be an effective treatment for patients with BRAF(V600E)-expressing PTMCs with aggressive clinical-pathologic features. Here, we summarize the clinical outcome, cancer genetics, and molecular mechanisms of PTMC.


BRAFV600E mutation; angiogenesis; clinical outcome; extracellular matrix; genetics; neck lymph node metastasis; papillary thyroid microcarcinoma; tumor microenvironment

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