Assessment of RET/PTC oncogene activation and clonality in thyroid nodules with incomplete morphological evidence of papillary carcinoma: a search for the early precursors of papillary cancer.

Abstract	Noninvasive thyroid nodules that exhibit borderline morphological signs of papillary cancer are difficult to diagnose and we do not know if they represent papillary carcinoma precursor lesions. Forty-six such nodules were analyzed for RET activation by immunohistochemistry and, in selected cases, by reverse transcriptase-polymerase chain reaction performed on RNA extracted after laser capture microdissection (LCM) of the tumor foci with and without papillary carcinoma features and positive RET immunoreactivity. RET immunoreactivity was identified, at least focally, in 30 of 46 (65.2%) of the nodules where it closely paralleled the morphological changes. Enough RNA was obtained after LCM in seven samples. RET/PTC1 or RET/PTC3 were detected in microscopic foci with papillary carcinoma features in most of the thyroid nodules (five of seven cases). No RET/PTC1 or RET/PTC3 rearrangements were detected in areas of the same tumors that lacked the cytological alterations. Analysis of clonality in the same nodules selected for LCM demonstrated that two were monoclonal and six were polyclonal. We conclude that RET activation closely parallels the morphological changes, that it is restricted to those areas of the tumor with the cytological alterations and that it is detectable in both mono- and polyclonal tumors. Although the finding of microscopic foci indicative of papillary carcinoma in a hyperplastic or adenomatous nodule does not justify the interpretation of the entire lesion as papillary carcinoma, it is possible that such foci may precede the development of invasive papillary cancer.
Authors	Alfredo Fusco, Gennaro Chiappetta, Pei Hui, Ginesa Garcia-Rostan, Lauren Golden, Barbara K Kinder, Deborah A Dillon, Ada Giuliano, Anna Maria Cirafici, Massimo Santoro, Juan Rosai, Giovanni Tallini
Journal	The American journal of pathology (Am J Pathol) Vol. 160 Issue 6 Pg. 2157-67 (Jun 2002) ISSN: 0002-9440 [Print] United States
PMID	12057919 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Drosophila Proteins Genetic Markers Membrane Proteins NCOA4 protein, human Nuclear Receptor Coactivators Oncogene Proteins Oncogene Proteins, Fusion Patched Receptors Patched-1 Receptor Proto-Oncogene Proteins Ptch1 protein, mouse Receptors, Cell Surface Transcription Factors Protein-Tyrosine Kinases Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases Ret protein, Drosophila Ret protein, mouse ret-PTC fusion oncoproteins, human
Topics	3T3 Cells Animals Base Sequence Carcinoma, Papillary (metabolism, pathology) Cloning, Molecular Drosophila Proteins Gene Expression Regulation, Neoplastic Genetic Markers Humans Membrane Proteins (biosynthesis, genetics) Mice Molecular Sequence Data Neoplasm Invasiveness (genetics) Nuclear Receptor Coactivators Oncogene Proteins (genetics, metabolism) Oncogene Proteins, Fusion (genetics, metabolism) Patched Receptors Patched-1 Receptor Protein-Tyrosine Kinases Proto-Oncogene Proteins (biosynthesis, genetics) Proto-Oncogene Proteins c-ret Rabbits Receptor Protein-Tyrosine Kinases (biosynthesis, genetics) Receptors, Cell Surface Reverse Transcriptase Polymerase Chain Reaction Thyroid Neoplasms (metabolism, pathology) Thyroid Nodule (metabolism, pathology) Transcription Factors

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