RESUMEN
BACKGROUND: Tumour metastasis has been associated with cancer stem cells, a small population with stem-like cells properties, higher rate of migration and metastatic potential compared to cells from the tumour bulk. Our aim was to evaluate the immunoexpression of the putative cancer stem cell biomarkers ALDH1 and CD44 in primary tumour and corresponding metastatic lymph nodes. METHODS: Tumour tissue specimens (n = 50) and corresponding metastatic lymph nodes (n = 25) were surgically obtained from 50 patients with oral squamous cell carcinoma and submitted to immunohistochemistry. CD44 and ALDH1 were semi-quantitatively scored according to the proportion and intensity of positive cells within the invasive front and metastatic lymph nodes as a whole. A combined score was obtained by multiplying both parameters and later dichotomized into a final score classified as low (≤2) or high (>2) immunoexpression. RESULTS: ALDH1 immunoexpression and CD44 immunoexpression were detected in both tumour sites, although the means of ALDH1 (P = .0985) and CD44 (P = .4220) cells were higher in metastasis compared to primary tumours. ALDH1high was positively associated (P = .0184) with angiolymphatic invasion, while CD44high was positively associated (P = .0181) with metastasis (N+). At multivariate analysis, CD44 significantly increased the odds of lymph node metastasis, regardless of T stage (OR = 8.24; 1.64-65.64, P = .0088). CONCLUSIONS: CD44 immunoexpression was a significant predictor of lymph node metastasis, while ALDH1high immunostaining was associated with angiolymphatic invasion. Altogether, it suggests that immunoexpression of CD44 and ALDH1 links the cancer stem cell phenotype with oral squamous cell carcinoma invasion and metastasis.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Receptores de Hialuranos/metabolismo , Isoenzimas/metabolismo , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/patología , Células Madre Neoplásicas/patología , Retinal-Deshidrogenasa/metabolismo , Familia de Aldehído Deshidrogenasa 1 , Carcinoma de Células Escamosas/genética , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática/genética , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/genética , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , PronósticoRESUMEN
Human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC), although strongly divergent results have been reported regarding the prevalence of HPV16 in different countries, whether this represents important differences in etiology remains unclear. Applying rigorous protocols for sample processing, we centrally evaluated 1,420 head and neck tumors (533 oropharynx, 395 oral cavity and 482 larynx) from studies conducted in the US, Europe and Brazil for mucosal HPV DNA and p16INK4a expression to evaluate regional heterogeneity in the proportion of HPV16-associated OPSCC and other head and neck cancer, and to assess covariates associated with the risk of HPV16-positive OPSCC. While majority of OPSCC in the US (60%) were HPV16-positive, this proportion was 31% in Europe and only 4% in Brazil (p < 0.01). Similar differences were observed for other head and neck tumors, ranging from 7% in the US and 5% in Europe, to 0% in South America. The odds of HPV16-positive OPSCC declined with increasing pack years of smoking (OR: 0.75; 95% CI: 0.64-0.87) and drink years of alcohol use (OR: 0.64; 95% CI: 0.54-0.76). These results suggest that while the contribution of HPV16 is substantial for the oropharynx, it remains limited for oral cavity and laryngeal cancers.
Asunto(s)
Biomarcadores de Tumor/biosíntesis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/biosíntesis , Neoplasias de Cabeza y Cuello/epidemiología , Papillomavirus Humano 16/genética , Biomarcadores de Tumor/genética , Brasil , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Europa (Continente) , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/virología , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 16/patogenicidad , Humanos , Estados UnidosRESUMEN
We briefly review the surgical approaches to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2 (medullary thyroid carcinoma/multiple endocrine neoplasia type 2). The recommended surgical approaches are usually based on the age of the affected carrier/patient, tumor staging and the specific rearranged during transfection codon mutation. We have focused mainly on young children with no apparent disease who are carrying a germline rearranged during transfection mutation. Successful management of medullary thyroid carcinoma in these cases depends on early diagnosis and treatment. Total thyroidectomy should be performed before 6 months of age in infants carrying the rearranged during transfection 918 codon mutation, by the age of 3 years in rearranged during transfection 634 mutation carriers, at 5 years of age in carriers with level 3 risk rearranged during transfection mutations, and by the age of 10 years in level 4 risk rearranged during transfection mutations. Patients with thyroid tumor >5 mm detected by ultrasound, and basal calcitonin levels >40 pg/ml, frequently have cervical and upper mediastinal lymph node metastasis. In the latter patients, total thyroidectomy should be complemented by extensive lymph node dissection. Also, we briefly review our data from a large familial medullary thyroid carcinoma genealogy harboring a germline rearranged during transfection Cys620Arg mutation. All 14 screened carriers of the rearranged during transfection Cys620Arg mutation who underwent total thyroidectomy before the age of 12 years presented persistently undetectable serum levels of calcitonin (<2 pg/ml) during the follow-up period of 2-6 years. Although it is recommended that preventive total thyroidectomy in rearranged during transfection codon 620 mutation carriers is performed before the age of 5 years, in this particular family the surgical intervention performed before the age of 12 years led to an apparent biochemical cure.
Asunto(s)
Carcinoma Medular/cirugía , Escisión del Ganglio Linfático , Neoplasia Endocrina Múltiple Tipo 2a/cirugía , Neoplasias de la Tiroides/cirugía , Calcitonina/sangre , Carcinoma Medular/genética , Carcinoma Neuroendocrino , Niño , Mutación de Línea Germinal/genética , Humanos , Neoplasia Endocrina Múltiple Tipo 2a/genética , Cuello , Proteínas Proto-Oncogénicas c-ret/genética , Neoplasias de la Tiroides/genéticaRESUMEN
OBJECTIVE: To standardize the design of individually fitted implants based on computed tomographic (CT) images for use in medialization laryngoplasty without intraoperative voice monitoring. STUDY DESIGN: Prospective tomographic and anatomical experimental study of 10 human cadaveric larynges. METHODS: CT scans of 10 excised human larynges were analyzed to define the shape and size of ideal implants for medialization laryngoplasty. Silicone implants were designed according to CT parameters and used in simulated laryngoplasties in the laryngeal specimens. The efficacy of each implant in providing adequate medialization of the vocal fold was evaluated. RESULTS: Diverse shapes and sizes of implants were obtained, reflecting variations in laryngeal anatomy. The implants enabled regular medialization of the entire extent of the free border of the vocal fold, including its posterior aspect. Medialization was considered adequate in all cases. CONCLUSIONS: This method proved to be a simple and efficient way to design individualized implants for medialization laryngoplasty, regardless of the size and shape of the larynx. LEVEL OF EVIDENCE: Not available.
Asunto(s)
Laringoplastia/instrumentación , Laringe/cirugía , Diseño de Prótesis , Implantación de Prótesis/instrumentación , Pliegues Vocales/cirugía , Anciano , Cadáver , Diseño Asistido por Computadora , Femenino , Humanos , Laringe/anatomía & histología , Laringe/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Siliconas , Tomografía Computarizada por Rayos X , Pliegues Vocales/anatomía & histología , Pliegues Vocales/diagnóstico por imagenRESUMEN
BACKGROUND: Oral cancer overexpressed 1 (ORAOV1) was found as a candidate oncogene in the 11q13 chromosomal region, based on its amplification and overexpression in oral cancer cell lines. Because gene amplification often leads to increased levels of gene expression, we aimed to verify the relationship between ORAOV1 gene status and mRNA expression primarily in oral squamous cell carcinoma (OSCC) by quantitative assay, correlating with clinical and pathological characteristics in patients. METHODS: Levels of ORAOV1 amplification and expression were evaluated by qPCR and RT-qPCR in OSCC cell lines and in tumor and non-tumoral surgical margins from 33 patients with OSCC. All subjects were smokers and habitual alcohol drinkers, mostly men above 40 years of age and with a single primary tumor. RESULTS: ORAOV1 exhibited increased gene expression levels as well as higher copy number in three OSCC cell lines with 11q13 amplified chromosomal region when compared with the OSCC cell line without the amplification (one-way ANOVA, P < 0.05). Weak correlation between ORAOV1 mRNA levels and DNA copy number was seen in tumor samples (Spearman, P = 0.07). Although ORAOV1 was amplified in tumor (Wilcoxon, P < 0.01), high levels of transcripts in margin did not reveal differences in comparison with tumor (Wilcoxon, P = 0.85). Aggressiveness and survival rate did not demonstrate statistical difference for both events in OSCC. CONCLUSION: The overexpression of ORAOV1 in non-tumoral margin samples can occur in the absence of amplification. The weak correlation between ORAOV1 amplification and expression in OSSC suggests that ORAOV1 expression can be regulated by mechanisms other than gene amplification.
Asunto(s)
Carcinoma de Células Escamosas/genética , Amplificación de Genes/genética , Neoplasias de la Boca/genética , Proteínas de Neoplasias/genética , Oncogenes/genética , Adulto , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Estudios de Casos y Controles , Línea Celular Tumoral , Cromosomas Humanos Par 11/genética , Variaciones en el Número de Copia de ADN/genética , ADN de Neoplasias/genética , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Metástasis Linfática/patología , Masculino , Neoplasias de la Boca/patología , Clasificación del Tumor , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios Prospectivos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de SupervivenciaRESUMEN
We briefly review the surgical approaches to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2 (medullary thyroid carcinoma/multiple endocrine neoplasia type 2). The recommended surgical approaches are usually based on the age of the affected carrier/patient, tumor staging and the specific rearranged during transfection codon mutation. We have focused mainly on young children with no apparent disease who are carrying a germline rearranged during transfection mutation. Successful management of medullary thyroid carcinoma in these cases depends on early diagnosis and treatment. Total thyroidectomy should be performed before 6 months of age in infants carrying the rearranged during transfection 918 codon mutation, by the age of 3 years in rearranged during transfection 634 mutation carriers, at 5 years of age in carriers with level 3 risk rearranged during transfection mutations, and by the age of 10 years in level 4 risk rearranged during transfection mutations. Patients with thyroid tumor >5 mm detected by ultrasound, and basal calcitonin levels >40 pg/ml, frequently have cervical and upper mediastinal lymph node metastasis. In the latter patients, total thyroidectomy should be complemented by extensive lymph node dissection. Also, we briefly review our data from a large familial medullary thyroid carcinoma genealogy harboring a germline rearranged during transfection Cys620Arg mutation. All 14 screened carriers of the rearranged during transfection Cys620Arg mutation who underwent total thyroidectomy before the age of 12 years presented persistently undetectable serum levels of calcitonin (<2 pg/ml) during the follow-up period of 2-6 years. Although it is recommended that preventive total thyroidectomy in rearranged during transfection codon 620 mutation carriers is performed before the age of 5 years, in this particular family the surgical intervention performed before the age of 12 years led to an apparent biochemical cure.
Asunto(s)
Niño , Humanos , Carcinoma Medular/cirugía , Escisión del Ganglio Linfático , /cirugía , Neoplasias de la Tiroides/cirugía , Calcitonina/sangre , Carcinoma Medular/genética , Mutación de Línea Germinal/genética , /genética , Cuello , Proteínas Proto-Oncogénicas c-ret/genética , Neoplasias de la Tiroides/genéticaRESUMEN
BACKGROUND: The aim of this study was to determine the predictive value for malignancy of microcalcifications determined by ultrasonography in thyroid nodules. METHODS: One hundred seventy-seven nodules were prospectively studied by ultrasonography and compared with their fine-needle aspirative biopsy. The association between the presence and type of calcification and cytologic findings was verified through the chi-square test or likelihood ratio. RESULTS: Thirty nodules showed calcification, of which 17 had fine calcifications, 3 had fine and gross calcifications, and 10 had only coarse calcification. Seven (41.18%) of 17 fine calcified nodules were malignant on cytology, 8 (47.06%) were benign, 1 (5.88%) was indeterminate, and 1 was suspect for malignancy. We found statistical significance between the presence of fine calcifications and malignancy (p = .001) and, in the 13 malignant nodule group, 8 (61.50%) had fine calcifications. CONCLUSION: This study suggests that microcalcifications were highly specific for malignancy and were present in 61% of the malignant nodules.
Asunto(s)
Biopsia con Aguja Fina/métodos , Calcinosis/diagnóstico por imagen , Calcinosis/patología , Lesiones Precancerosas/diagnóstico por imagen , Lesiones Precancerosas/patología , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , Adulto , Distribución por Edad , Anciano , Distribución de Chi-Cuadrado , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Funciones de Verosimilitud , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Distribución por Sexo , Nódulo Tiroideo/epidemiología , Ultrasonografía IntervencionalRESUMEN
OBJECTIVES/HYPOTHESIS: To analyze clinical and epidemiological features of neck nerve schwannomas, with emphasis on the neurologic outcome after surgical excision sparing as much of nerve fibers as possible with enucleation technique. STUDY DESIGN: Retrospective study. METHODS: Review of medical records from 1987 to 2006 of patients with neck nerve schwannomas, treated in a single institution. RESULTS: Twenty-two patients were identified. Gender distribution was equal and age ranged from 15 to 61 years (mean: 38.6 years). Seven vagal, four brachial plexus, four sympathetic trunk, three cervical plexus, and two lesions on other sites could be identified. Most common symptom was neck mass. Local or irradiated pain also occurred in five cases. Median growing rate of tumors was 3 mm per year. Nerve paralysis was noted twice (a vagal schwannoma and a hypoglossal paralysis compressed by a vagal schwannoma). Different techniques were employed, and seven out of nine patients kept their nerve function (78%) after enucleation. No recurrence was observed in follow-up. CONCLUSIONS: Schwannomas should be treated surgically because of its growing potential, leading to local and neural compression symptoms. When possible, enucleation, which was employed in 10 patients of this series, is the recommended surgical option, allowing neural function preservation or restoration in most instances. This is especially important in the head and neck, where denervation may have a significant impact on the quality of life.