Telomerase expression and proliferative activity suggest a stem cell role for thyroid solid cell nests.
Solid cell nests of the human thyroid gland are composed of main cells and C cells. In order to investigate the putative stem cell nature of the role for solid cell nests, we evaluated the histological features, and the immunohistochemical expression of p63, bcl-2, telomerase catalytic subunit, and two proliferative markers (Ki-67 and minichromosome maintenance protein 2), in a series of 24 cases of solid cell nests. Proliferative indices were determined in (a) solid cell nests, (b) thyroid follicular cells in the vicinity of solid cell nests within a low-power field, and (c) distant thyroid tissue, at a distance of at least three low-power fields from solid cell nests. In 15 cases of solid cell nests (62.5%), mixed follicles were observed; papillary formations were observed in four cases (16.6%), and ciliated cells were observed in the lining of microcysts associated with two cases (8.3%). Salivary gland-type tissue, cartilage islands, adipose and fibrous tissues, and small nerves were also associated with some cases of solid cell nests. We observed that the main cells of the solid cell nests express consistently telomerase, although at lower levels than p63, and show strong cytoplasmic immunoreactivity for bcl-2, which is associated with an increased differentiation potential. We also observed that despite their relative low proliferative index, main cells of the solid cell nests display higher proliferation than follicular cells in the vicinity and follicular cells in more distant thyroid tissue. We conclude that main cells of the solid cell nests apparently harbor the minimal properties of a stem cell phenotype (capacity for both self-renewal, conferred by telomerase activity, and differentiation to one or more than one type of specialized cells, given by the high expression of p63 and bcl-2) and may thus represent a pool of stem cells of the adult thyroid.
Preto
Ana
A
Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.
Cameselle-Teijeiro
José
J
Moldes-Boullosa
Julio
J
Soares
Paula
P
Cameselle-Teijeiro
Jorge F
JF
Silva
Paula
P
Reis-Filho
Jorge S
JS
Reyes-Santías
Rosa M
RM
Alfonsín-Barreiro
Natividad
N
Forteza
Jerónimo
J
Sobrinho-Simões
Manuel
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division; D004268:DNA-Binding Proteins; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000032:analysis; D010750:Phosphoproteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013234:Stem Cells / Q000737:chemistry / Q000502:physiology; D019098:Telomerase / Q000096:biosynthesis*; D013961:Thyroid Gland / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology; D015534:Trans-Activators / Q000032:analysis; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D019098:Telomerase; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2