RESUMO
CONTEXT: A better means to accurately identify malignant thyroid nodules and to distinguish them from benign tumors is needed. We previously identified markers for detecting thyroid malignancy, with sensitivity estimated at or close to 100%. One lingering problem with these markers was that false positives occurred with Hürthle cell adenomas (HCA) which lowered test specificity. METHODS: To locate accurate diagnostic markers, we profiled in depth the transcripts of a HCA and a Hürthle cell carcinoma (HCC). From 1146 differentially expressed genes, 18 transcripts specifically expressed in HCA were tested by quantitative PCR in a wide range of thyroid tumors (n = 76). Sensibility and specificity were calculated using receiver operating characteristic (ROC). Selected markers were further validated in an independent set of thyroid tumors (n = 82) by immunohistochemistry. To define the panel that would yield best diagnostic accuracy, these markers were tested in combination with our previous identified markers. RESULTS: Seventeen of the 18 genes showed statistical significance based on a mean relative level of expression (P < 0.05). KLK1 (sensitivity = 0.97) and PVALB (sensitivity = 0.94) were the best candidate markers. The combination of PVALB and C1orf24 increased specificity to >97% and maintained sensitivity for detection of carcinoma. CONCLUSION: We identified tumor markers that can be used in combination for a more accurate preoperative diagnosis of thyroid nodules and for postoperative diagnosis of thyroid carcinoma in tumor sections. This improved test would help physicians rapidly focus treatment on true malignancies and avoid unnecessary treatment of benign tumors, simultaneously improving medical care and reducing costs.
Assuntos
Adenoma Oxífilo/diagnóstico , Adenoma Oxífilo/genética , Parvalbuminas/genética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Adenoma Oxífilo/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biópsia por Agulha Fina , Análise por Conglomerados , Expressão Gênica , Humanos , Imuno-Histoquímica , Parvalbuminas/metabolismo , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Calicreínas Teciduais/genética , Calicreínas Teciduais/metabolismoRESUMO
Renal cell tumors have been shown to be associated with secretory products, including renin, but the frequency of renin expression is not known. To investigate renin expression in epithelial renal neoplasms, we examined a series of 89 adult renal tumors with granular cells using a monoclonal antiserum to detect the hormone by immunohistochemistry (IHC) and their association with hypertension. We found that 25 of 89 tumors (28.1%) contained immunoreactivity for renin. Oncocytomas had the highest percentage of cases with renin expression: 8 of 13 (61.5%), all of these with diffuse immunostaining. Renin was detected in 31.6% of 38 chromophobe carcinomas and in 12.5% of 24 conventional carcinomas. Renin was not detected in collecting duct carcinomas or in mucinous tubular and spindle cell carcinomas. Systemic hypertension was detected in 11 of 25 (44%) patients with renin expression and in 32 of 64 (50%) patients without renin immunolabeling (p=0.64). After tumor resection, patients with renin expression and high blood pressure showed no hypertension remission. In conclusion, renin is frequently expressed in renal epithelial neoplasms with granular cells, mainly in oncocytomas, but this renin appears clinically inactive.
Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Renina/metabolismo , Adenoma Oxífilo/complicações , Adenoma Oxífilo/metabolismo , Adenoma Oxífilo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/patologia , Citoplasma/metabolismo , Citoplasma/patologia , Grânulos Citoplasmáticos/metabolismo , Feminino , Humanos , Hipertensão/complicações , Técnicas Imunoenzimáticas , Rim/metabolismo , Rim/cirurgia , Neoplasias Renais/complicações , Neoplasias Renais/patologia , Túbulos Renais Coletores/metabolismo , Túbulos Renais Coletores/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To correlate the subjective AgNOR counting method and DNA content with histologic diagnoses of thyroid cancer and invasion. STUDY DESIGN: Eighty-one consecutive cases of thyroid carcinoma were selected for DNA and AgNOR analysis. The diagnoses were: papillary carcinoma (n = 40), follicular carcinoma (n = 31), Hürthle cell adenocarcinoma (n = 4), and undifferentiated carcinoma (n = 6). Seven normal thyroids were used as controls. DNA quantitative measurement was performed with Vidas 2.0 software (Kontron Bildanalyse, Munich, Germany) connected to an MPM 210 photometer microscope (Carl Zeiss, Oberkochen, Germany). The DNA index was obtained using histograms. Counting the NORs was performed by subjectively counting the NORs in 200 malignant cells. RESULTS: DNA ploidy analysis showed all Hürthle cell adenocarcinomas, 21 (67%)follicular tumors, 23 (57%) papillary tumors and 4 (67%) undifferentiated carcinomas to be aneuploid. DNA analysis correlated with histologic type of the tumor (p = 0.032). There was no statistical significance to the AgNOR counting variables studied. Statistical analysis showed correlation between ploidy and histologic diagnosis, but not AgNOR counting, to have prognostic value. CONCLUSION: DNA ploidy is more useful than subjective counting of NORs as an adjunct method for thyroid lesion analysis.