Molecular diagnosis of a BRAF papillary thyroid carcinoma with multiple chromosome abnormalities and rare adrenal and hypothalamic metastases.
OBJECTIVE
Molecular characterization of thyroid tumors is rarely applied to patient management. Our aim was to demonstrate the application of molecular and cell biology to patient care.


METHODS
Clinical and molecular case study.


RESULTS
A 57-year-old man with papillary thyroid carcinoma presented with adrenal and several other presumed metastases, pulmonary nodules, and mediastinal lymphadenopathy. Bronchial carcinoma was entertained for the pulmonary lesions because of a tobacco history. Mediastinal lymph node biopsy was nondiagnostic. Cells from the biopsy were grown in tissue culture and characterized by immunocytochemical (ICC), allele-specific polymerase chain reaction (PCR), reverse transcription (RT)-PCR, DNA sequencing, and cytogenetics. A panel of agents were tested the cells for tumoricidal activity. The cells expressed thyroid-specific markers [thyroid-stimulating hormone receptor (TSH-R), thyroglobulin (TG), sodium iodide symporter (NIS)] and markers [thyroid transcription factor-1 (TTF-1), cytokeratin-7, epidermal growth factor receptor (EGF-R)] present in the primary tumor and adrenal metastasis. The BRAF V600E mutation was detected. The karyotype was 44-48,XY, + der(1) t(1;9)(p13;p13),add(9)(p13),-17,-18, + 0-3mar[cp20]. Lovastatin, gefitinib, paclitaxel, depsipeptide, and 17-AAG inhibited the growth of the cultured cells. Combinations of two or three drugs produced additive or synergistic effects depending upon the combination.


CONCLUSIONS
Unusual metastases may be associated with multiple molecular and cytogenetic abnormalities. Thus, molecular and cell-biological studies can allow otherwise difficult thyroid tumor diagnosis and may be used for targeted, individualized selection of potential treatments.
Copland
John A
JA
Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
Marlow
Laura A
LA
Williams
Sandra F
SF
Grebe
Stefan K
SK
Gumz
Michelle L
ML
Maples
William J
WJ
Silverman
Victor E
VE
Smallridge
Robert C
RC
D000310:Adrenal Gland Neoplasms / Q000556:secondary*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000235:genetics / Q000556:secondary; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D006801:Humans; D007029:Hypothalamic Neoplasms / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf