Patient case: 56-year-old female with basal cell carcinoma; genetic feature: PTCH1

Clinical trial: Study of Molecular Pathways in Medullary Thyroid Carcinoma and Correlation of Molecular Data With Clinical Behavior of the MTC in Individuals Patients

Summary: 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.

Detailed description: 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.

Eligibility: -  INCLUSION CRITERIA:
  Patients must have confirmed diagnosis of C-cell hyperplasia, primary MTC, or metastatic MTC with archived pathology specimens available at Washington University.

Relevance to patient case: not relevant