Background:~Medullary thyroid carcinoma (MTC) is a rare malignancy, occurring either as a sporadic disease (75% of cases), or in a hereditary pattern as multiple endocrine neoplasia (MEN) type 2 (MEN2A or MEN2B) or familial medullary thyroid carcinoma (FMTC). The MTC arises from the neural crest C-cells and in hereditary cases the first pathological disorder is C-cell hyperplasia (CCH) Most patients with MTC have advanced disease at the time of diagnosis.~Chemotherapy and external beam radiotherapy have been minimally effective. Molecular targeted therapeutics (MTTs) and other receptor kinases in patients with advanced MTC have demonstrated activity.~Despite some clinical responses, the collection of tumor tissues and autologous normal tissues has been virtually non-existent. Thus, laboratory studies defining affected molecular targets and downstream pathways, and molecular data providing direction for future clinical trials has yet to occur.~Data from molecular studies of tumor tissue of hereditary or sporadic MTC patients will assist in predicting clinical behavior and the biology of MTC in predicting response to a given MTT, and in designing combination clinical trials.~Objectives:~Clarify how normal molecular pathways are altered by mutations in the RET protooncogene. Including additional genetic mutations and unidentified chromosomal translocations.~Correlate results from molecular analyses of MTC tissue with patient s clinical course.~Define how the molecular and clinical data will be useful in designing targeted therapy for patients with MTC.~Eligibility:~Patients must have confirmed diagnosis of C-cell hyperplasia, primary MTC, or metastatic MTC with archived pathology specimens available at Washington University.~Design:~Paraffin blocks of MTC tissues from archival samples at Washington University Department of Pathology will be selected.~H&E slide from selected tissue blocks will be examined for molecular study suitability.~Necessary tissue samples from blocks will have molecular studies, including, gene arrays, array comparative genomic hybridization, immunohistochemistry, and sequencing.~Retrospective chart review will occur to obtain relevant clinical information.
Background:~Medullary thyroid carcinoma (MTC) is a rare malignancy, occurring either as a sporadic disease (75% of cases), or in a hereditary pattern as multiple endocrine neoplasia (MEN) type 2 (MEN2A or MEN2B) or familial medullary thyroid carcinoma (FMTC). The MTC arises from the neural crest C-cells and in hereditary cases the first pathological disorder is C-cell hyperplasia (CCH) Most patients with MTC have advanced disease at the time of diagnosis.~Chemotherapy and external beam radiotherapy have been minimally effective. Molecular targeted therapeutics (MTTs) and other receptor kinases in patients with advanced MTC have demonstrated activity.~Despite some clinical responses, the collection of tumor tissues and autologous normal tissues has been virtually non-existent. Thus, laboratory studies defining affected molecular targets and downstream pathways, and molecular data providing direction for future clinical trials has yet to occur.~Data from molecular studies of tumor tissue of hereditary or sporadic MTC patients will assist in predicting clinical behavior and the biology of MTC in predicting response to a given MTT, and in designing combination clinical trials.~Objectives:~Clarify how normal molecular pathways are altered by mutations in the RET protooncogene. Including additional genetic mutations and unidentified chromosomal translocations.~Correlate results from molecular analyses of MTC tissue with patient s clinical course.~Define how the molecular and clinical data will be useful in designing targeted therapy for patients with MTC.~Eligibility:~Patients must have confirmed diagnosis of C-cell hyperplasia, primary MTC, or metastatic MTC with archived pathology specimens available at Washington University.~Design:~Paraffin blocks of MTC tissues from archival samples at Washington University Department of Pathology will be selected.~H&E slide from selected tissue blocks will be examined for molecular study suitability.~Necessary tissue samples from blocks will have molecular studies, including, gene arrays, array comparative genomic hybridization, immunohistochemistry, and sequencing.~Retrospective chart review will occur to obtain relevant clinical information.