RESUMEN
A series of 1378 intra-operative frozen diagnoses performed in our department over two years (1998-1999) was studied in order to assess the agreement with the diagnosis on formalin-fixed, paraffin-embedded sections. In selected cases, a rapid immunostaining (IS) method was applied on frozen sections to solve diagnostic problems. Rapid IS allowed us to determine the histotype of poorly differentiated neoplasms, the origin of lung nodules and the presence of nests of neoplastic cells on resection margins. The method delayed the answer by about 20 minutes, and was always previously arranged with the surgeon. Rapid IS method was performed using routine reagents and was not repeated on formalin-fixed, paraffin-embedded sections of the same cases, thus avoiding additional costs.
Asunto(s)
Biomarcadores de Tumor/análisis , Secciones por Congelación , Inmunohistoquímica/métodos , Neoplasias/diagnóstico , Biotinilación , Carcinoma de Células Pequeñas/química , Carcinoma de Células Pequeñas/diagnóstico , Carcinoma de Células Pequeñas/patología , Diferenciación Celular , Diagnóstico Diferencial , Femenino , Humanos , Técnicas para Inmunoenzimas , Periodo Intraoperatorio , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Masculino , Neoplasias/química , Neoplasias/patología , Neoplasias/cirugía , Adhesión en Parafina , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela , Factores de TiempoRESUMEN
BACKGROUND: We have analysed the distribution of the five somatostatin receptors (sst1-5) by immunohistochemistry in a large retrospective series of 51 medullary carcinoma of the thyroid (MCT) specimens and correlated the pattern of sst expression with expression of somatostatin (SRIF) peptide, tumour pathology and clinical outcome. MEASUREMENTS: Immunohistochemistry was performed with rabbit polyclonal antipeptide antibodies directed against the extracellular domains or cytoplasmic tail of human (h) sst1-5. SRIF immunoreactivity was investigated in parallel paraffin sections. RESULTS: Eighty-five percent of the tumours were positive for one or more sst, localized to both tumour cells as well as surrounding peritumoural structures, especially blood vessels. Forty-nine percent of the tumours were positive for sst1, 43% for sst2, 47% for sst3, 4% for sst4, and 57% for sst5. Fifty-one percent of tumours expressed one or two sst subtypes; 33% were positive for three or more sst isoforms. All five sst receptors were detected in only two cases. Tumours expressing octreotide sensitive subtypes (sst2,3,5) accounted for 75% of the series. 50% of the tumours co-expressed SRIF suggesting tumour cell regulation by endogenous SRIF via paracrine/autocrine circuits. There was no correlation between sst1-5 expression and age, sex, tumour size or stage, histological type or clinical outcome. Simultaneous analysis of primary tumour and lymph node metastases revealed a similar pattern of sst immunoreactivity indicating that sst expression is not modified in the course of disease progression. CONCLUSIONS: With the exception of sst4, medullary carcinoma of the thyroid display a rich but heterogeneous expression of sst subtypes. Immunohistochemical typing of sst receptor expression using specific antireceptor antibodies represents an ideal approach for characterizing sst subtype expression in medullary carcinoma of the thyroid for optimizing receptor targeted diagnosis and therapy with somatostatin analogs.
Asunto(s)
Carcinoma Medular/química , Receptores de Somatostatina/análisis , Neoplasias de la Tiroides/química , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Medular/patología , Distribución de Chi-Cuadrado , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Somatostatina/análisis , Glándula Tiroides/química , Neoplasias de la Tiroides/patología , Resultado del TratamientoRESUMEN
Somatostatin receptors type 2 (sst2) have been frequently detected in neuroendocrine tumors and bind somatostatin analogues, such as octreotide, with high affinity. Receptor autoradiography, specific mRNA detection and, more recently, antisst2 polyclonal antibodies are currently employed to reveal sst2. The aim of the present study was to investigate by three different techniques the presence of sst2 in a series of 26 neuroendocrine tumors of the lung in which fresh frozen tissue and paraffin sections were available. It was possible, therefore, to compare, in individual cases, RNA analysis studied by reverse transcriptase polymerase chain reaction (RT-PCR), in situ hybridization (ISH), and immunohistochemistry. A series of 20 nonneuroendocrine lung carcinoma samples served as controls. RT-PCR was positive for sst2 in 22 of 26 samples, including 15 of 15 typical carcinoids, 5 of 6 atypical carcinoids, and 2 of 5 small-cell carcinomas. The sst2 mRNA signal obtained by RT-PCR was strong in the majority (87%) of typical carcinoids and of variable intensity in atypical carcinoids and small-cell carcinomas. A weakly positive signal was observed in 5 of 20 control samples. In immunohistochemistry, two different antibodies (anti-sst2) were employed, including a monoclonal antibody, generated in the Department of Pathology, University of Turin. In the majority of samples a good correlation between sst2 mRNA (as detected by RT-PCR) and sst2 protein expression (as detected by immunohistochemistry) was observed. However, one atypical carcinoid and one small-cell carcinoma had focal immunostaining but no RT-PCR signal. ISH performed in selected samples paralleled the results obtained with the other techniques. A low sst2 expression was associated with high grade neuroendocrine tumors and with aggressive behavior. It is concluded that 1) neuroendocrine tumors of the lung express sst2, and there is a correlation between the mRNA amount and the degree of differentiation; 2) immunohistochemistry and ISH are reliable tools to demonstrate sst2 in these tumors; and 3) sst2 identification in tissue sections may provide information on the diagnostic or therapeutic usefulness of somatostatin analogues in individual patients with neuroendocrine tumors.