title: Detection of hematogenic and lymphogenic tumor cell dissemination in patients with medullary thyroid carcinoma by cytokeratin 20 and preprogastrin-releasing peptide RT-PCR.
abstract: Despite an extensive surgical approach only 50% of the patients with medullary thyroid carcinoma (MTC) are biochemically cured. The failure to cure a larger number of patients is a result of the early dissemination of MTC. The present study evaluates two RT-PCR based assays for the detection of disseminated tumor cells in blood, bone marrow and lymph node samples of patients with MTC. Frozen tissue and blood samples of 19 patients with MTC and 61 cervical lymph nodes of these patients were obtained intraoperatively during thyroidectomy and lymphadenectomy. Preoperative bone marrow samples were obtained from 8 patients with MTC. An expression of CK20 and preproGRP was found in all MTC tissue samples. Using CK20-PCR, disseminated MTC cells were detected in 67% of the cervical lymph nodes of patients with MTC, compared to 72% involved lymph nodes, detected by preproGRP-PCR. In 16 of 61 nodes (26%) each PCR-system detected disseminated tumor cells in histologically tumor-free lymph nodes. Disseminated tumor cells were detected with CK20-PCR and preproGRP in 5 of 18 (28%) preoperative blood samples, each. The detection of a hematogenic tumor cell dissemination by preproGRP correlated significantly with the tumor stages (p = 0.019). Circulating MTC cells were found in 3 of 8 bone marrow samples with CK20-PCR, compared to 1 of 8 samples with preproGRP-PCR. Both PCR assays are highly sensitive to detect disseminated MTC cells in blood, bone marrow and lymph node samples. Our results of disseminated MTC cells in 26% of histologically tumor-free cervical lymph nodes and in 28% of the blood samples of patients with MTC might therefore explain the low biochemical cure rates.
authors.affiliation: Department of Surgery, University of Heidelberg, Germany. theresia_weber@med.uni-heidelberg.de
authors.forename: Theresia
authors.initials: T
authors.lastname: Weber
authors.forename: Jeannine
authors.initials: J
authors.lastname: Lacroix
authors.forename: Stefan
authors.initials: S
authors.lastname: Wörner
authors.forename: Helgard
authors.initials: H
authors.lastname: Weckauf
authors.forename: Steffi
authors.initials: S
authors.lastname: Winkler
authors.forename: Ulf
authors.initials: U
authors.lastname: Hinz
authors.forename: Tobias
authors.initials: T
authors.lastname: Schilling
authors.forename: Karin
authors.initials: K
authors.lastname: Frank-Raue
authors.forename: Ernst
authors.initials: E
authors.lastname: Klar
authors.forename: Magnus von
authors.initials: Mv
authors.lastname: Knebel Doeberitz Mv
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics* / Q000378:metabolism; D053554:Keratin-20; D008198:Lymph Nodes / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; D053554:Keratin-20; D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C047897:gastrin-releasing peptide precursor