ABSTRACT
To develop a new therapeutic strategy against thyroid cancer (TC), the expression of both substance P (SP) and neurokinin-1 receptor (NK-1R) must be demonstrated in TC cells. This study aims to examine by immunohistochemistry, the localization of SP and the NK-1R in human TC samples (papillary, follicular, medullary, anaplastic), in metastasis and in healthy thyroid samples. SP and the NK-1R were expressed in all normal and TC samples. In healthy glands, SP was located in follicular cells (nucleus) and colloid and NK-1R in follicular cells (cytoplasm) and stroma. In TC samples, SP was visualized in follicular cells (nucleus and cytoplasm), stroma and colloid and NK-1R in follicular cells (cytoplasm), stroma and colloid. A semiquantitative scoring system (Allred Unit Scoring System) was applied. The expression (Allred total score) of SP and NK-1R was weaker in normal thyroid glands than in TC. In comparison with TC samples, a lower intensity/proportion of SP (nucleus and cytoplasm of follicular cells; stroma) was observed in normal samples. By contrast, in the colloid of TC samples the presence of SP was lower than in normal samples. In comparison with TC samples, the presence of the NK-1R in the cytoplasm of follicular cells and colloid was lower in normal thyroid samples, whereas the expression of this receptor in the stroma was higher. The results reported in this study suggest that the NK-1R could be a new target for the treatment of TC and use of the NK-1R antagonists could serve as a new anti-TC therapeutic strategy.
Subject(s)
Receptors, Neurokinin-1/metabolism , Substance P/metabolism , Thyroid Neoplasms/metabolism , Cell Nucleus/metabolism , Cytoplasm/metabolism , Female , Humans , Immunohistochemistry , Male , Statistics, Nonparametric , Thyroid Epithelial Cells/metabolism , Thyroid Gland/cytology , Thyroid Gland/pathology , Thyroid Neoplasms/pathologyABSTRACT
BACKGROUND: PRPS1 encodes isoform I of phosphoribosylpyrophosphate synthetase (PRS-I), a key enzyme in nucleotide biosynthesis. Different missense mutations in PRPS1 cause a variety of disorders that include PRS-I superactivity, nonsyndromic sensorineural hearing impairment, Charcot-Marie-Tooth disease, and Arts syndrome. It has been proposed that each mutation would result in a specific phenotype, depending on its effects on the structure and function of the enzyme. METHODS: Thirteen Spanish unrelated families segregating X-linked hearing impairment were screened for PRPS1 mutations by Sanger sequencing. In two positive pedigrees, segregation of mutations was studied, and clinical data from affected subjects were compared. RESULTS: We report two novel missense mutations in PRPS1, p.Ile275Thr and p.Gly306Glu, which were found in the propositi of two unrelated Spanish families, both subjects presenting with nonsyndromic hearing impairment. Further investigation revealed syndromic features in other hemizygous carriers from one of the pedigrees. Sequencing of genes that are functionally related to PRPS1 did not reveal any candidate variant that might act as a phenotype modifier. CONCLUSION: This case of intrafamilial phenotypic variation associated with a single PRPS1 mutation complicates the genotype-phenotype correlations, which makes genetic counseling of mutation carriers difficult because of the wide spectrum of severity of the associated disorders.
Subject(s)
Genetic Counseling , Hearing Loss/genetics , Mutation , Ribose-Phosphate Pyrophosphokinase/genetics , Adolescent , Adult , Amino Acid Sequence , Chromosomes, Human, X , Deafness/genetics , Family Health , Female , Genetic Association Studies , Genetic Testing , Hemizygote , Heterozygote , Humans , Male , Molecular Sequence Data , Mutation, Missense , Pedigree , Phenotype , Sequence Homology, Amino Acid , SpainABSTRACT
El tumor carcinoide atípico de laringe es una neoplasia muy poco frecuente. Presentamos el caso de un varón de 67 años de edad con un tumor carcinoide atípico de laringe y metástasis en un ganglio linfático cervical. Se describen los hallazgos histológicos convencionales de esta neoplasia, enfatizando la necesidad del estudio inmunohistoquímico para su diagnóstico diferencial con el paraganglioma laríngeo. Es crucial el diagnóstico correcto, porque el tratamiento y el pronóstico son diferentes para ambas entidades ya que, como ocurrió en el presente caso, el diagnóstico en la pieza laríngea indicó un vaciamiento ganglionar cervical funcional homolateral en el que se identificó una metástasis de esta neoplasia (AU)
