Differentially expressed proteins in positive versus negative HNSCC lymph nodes.

BACKGROUND: Lymph node metastasis is one of the most important prognostic factors in head and neck squamous cell carcinomas (HNSCCs) and critical for delineating their treatment. However, clinical and histological criteria for the diagnosis of nodal status remain limited. In the present study, we aimed to characterize the proteomic profile of lymph node metastasis from HNSCC patients. METHODS: In the present study, we used one- and two-dimensional electrophoresis and mass spectrometry analysis to characterize the proteomic profile of lymph node metastasis from HNSCC. RESULTS: Comparison of metastatic and non-metastatic lymph nodes showed 52 differentially expressed proteins associated with neoplastic development and progression. The results reinforced the idea that tumors from different anatomical subsites have dissimilar behaviors, which may be influenced by micro-environmental factor including the lymphatic network. The expression pattern of heat shock proteins and glycolytic enzymes also suggested an effect of the lymph node environment in controlling tumor growth or in metabolic reprogramming of the metastatic cell. Our study, for the first time, provided direct evidence of annexin A1 overexpression in lymph node metastasis of head and neck cancer, adding information that may be useful for diagnosing aggressive disease. CONCLUSIONS: In brief, this study contributed to our understanding of the metastatic phenotype of HNSCC and provided potential targets for diagnostic in this group of carcinomas.

ATM, BCL2, and TGFß Gene Polymorphisms as Radiotherapy Outcome Biomarkers in Head and Neck Squamous Cell Carcinoma Patients.

AIMS: Polymorphisms in cell cycle genes are considered prognostic as radiosensitivity markers in patients with head and neck squamous cell carcinoma. Therefore, we aimed to investigate the relationship of ATM 5557G>A, ATM IVS62 + 60G>A, TP53 215G>C, BCL2-938C>A, TGFß-509C>T, and TGFß 29C>T with radiotherapy response. MATERIALS AND METHODS: Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism in 210 patients with oral cavity/oropharyngeal carcinoma and 101 patients with laryngeal tumors. RESULTS: In irradiated oral cavity/oropharyngeal tumors, the ATM IVS62 + 60G>A AA genotype significantly increased local recurrence risk (odds ratio [OR] = 4.43; confidence interval [CI] = 1.22-16.13) and the BCL2-938C>A C allele and the TGFß-509C>T T allele were associated with worse disease-specific survival (hazard ratio [HR] = 0.46; CI = 0.24-0.90 and HR = 2.20; CI = 1.12-4.29, respectively). In irradiated laryngeal carcinoma, the TGFß 29C>T C allele was associated with increased local recurrence risk (OR = 0.09; CI = 0.02-0.53), death rate (OR = 0.18; CI = 0.04-0.86), and worse local disease-free and disease-specific survival rates (HR = 0.13; CI = 0.03-0.59 and HR = 0.21; CI = 0.07-0.60, respectively), while the BCL2-938C>A C allele was related to a worse disease-specific survival (HR = 0.32; CI = 0.12-0.83). DISCUSSION: These results can help individualize treatment according to a patient's genetic markers. We demonstrated that ATM IVS62 + 60G>A, TGFß 29C>T, TGFß-509C>T, and BCL2-938C>A can function as biomarkers of tumor radiosensitivity, being candidates for a predictive genetic profile of radiotherapy response.

Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.

We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10-8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10-9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

PROX1 gene is differentially expressed in oral cancer and reduces cellular proliferation.

Homeobox genes are a family of transcription factors that play a pivotal role in embryogenesis. Prospero homeobox 1 (PROX1) has been shown to function as a tumor suppressor gene or oncogene in various types of cancer, including oral squamous cell carcinoma (OSCC). We have previously identified PROX1 as a downregulated gene in OSCC. The aim of this study is to clarify the underlying mechanism by which PROX1 regulates tumorigenicity of OSCC cells. PROX1 mRNA and protein expression levels were first investigated in 40 samples of OSCC and in nontumor margins. Methylation and amplification analysis was also performed to assess the epigenetic and genetic mechanisms involved in controlling PROX1 expression. OSCC cell line SCC9 was also transfected to stably express the PROX1 gene. Next, SCC9-PROX1-overexpressing cells and controls were subjected to proliferation, differentiation, apoptosis, migration, and invasion assays in vitro. OSCC samples showed reduced PROX1 expression levels compared with nontumor margins. PROX1 amplification was associated with better overall survival. PROX1 overexpression reduces cell proliferation and downregulates cyclin D1. PROX1-overexpressing cells also exhibited reduced CK18 and CK19 expression and transcriptionally altered the expression of WISP3, GATA3, NOTCH1, and E2F1. Our results suggest that PROX1 functions as a tumor suppressor gene in oral carcinogenesis.

Four-gene expression model predictive of lymph node metastases in oral squamous cell carcinoma.

BACKGROUND: Previous knowledge of cervical lymph node compromise may be crucial to choose the best treatment strategy in oral squamous cell carcinoma (OSCC). Here we propose a set four genes, whose mRNA expression in the primary tumor predicts nodal status in OSCC, excluding tongue. MATERIAL AND METHODS: We identified differentially expressed genes in OSCC with and without compromised lymph nodes using Differential Display RT-PCR. Known genes were chosen to be validated by means of Northern blotting or real time RT-PCR (qRT-PCR). Thereafter we constructed a Nodal Index (NI) using discriminant analysis in a learning set of 35 patients, which was further validated in a second independent group of 20 patients. RESULTS: Of the 63 differentially expressed known genes identified comparing three lymph node positive (pN +) and three negative (pN0) primary tumors, 23 were analyzed by Northern analysis or RT-PCR in 49 primary tumors. Six genes confirmed as differentially expressed were used to construct a NI, as the best set predictive of lymph nodal status, with the final result including four genes. The NI was able to correctly classify 32 of 35 patients comprising the learning group (88.6%; p = 0.009). Casein kinase 1alpha1 and scavenger receptor class B, member 2 were found to be up regulated in pN + group in contrast to small proline-rich protein 2B and Ras-GTPase activating protein SH3 domain-binding protein 2 which were upregulated in the pN0 group. We validated further our NI in an independent set of 20 primary tumors, 11 of them pN0 and nine pN + with an accuracy of 80.0% (p = 0.012). CONCLUSIONS: The NI was an independent predictor of compromised lymph nodes, taking into the consideration tumor size and histological grade. The genes identified here that integrate our "Nodal Index" model are predictive of lymph node metastasis in OSCC.

Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients.

BACKGROUND: To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC). PATIENTS AND METHODS: We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 oropharynx and 4 hypopharynx SCC and 65 matched adjacent mucosa, available for study, were also included. For survival analysis, patients were categorized as positive or negative for each Smad, according to median mRNA expression. We also performed real-time quantitative PCR (QRTPCR) to asses the pattern of TGFbeta1, TGFbeta2, TGFbeta3 in oral SCC. RESULTS: Our results showed that Smad2 and Smad6 mRNA expression were both associated with survival in Oral SCC patients. Cox Multivariate analysis revealed that Smad6 positivity and Smad2 negativity were both predictive of good prognosis for oral SCC patients, independent of lymph nodal status (P = 0.003 and P = 0.029, respectively). In addition, simultaneously Smad2- and Smad6+ oral SCC group of patients did not reach median overall survival (mOS) whereas the mOS of Smad2+/Smad6- subgroup was 11.6 months (P = 0.004, univariate analysis). Regarding to TGFbeta isoforms, we found that Smad2 mRNA and TGFbeta1 mRNA were inversely correlated (p = 0.05, R = -0.33), and that seven of the eight TGFbeta1+ patients were Smad2-. In larynx SCC, Smad7- patients did not reach mOS whereas mOS of Smad7+ patients were only 7.0 months (P = 0.04). No other correlations were found among Smad expression, clinico-pathological characteristics and survival in oral, larynx, hypopharynx, oropharynx or the entire head and neck SCC population. CONCLUSION: Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection. The underlying mechanism which involves aberrant TGFbeta signaling should be better clarified in the future.

Genomics and proteomics approaches to the study of cancer-stroma interactions.

BACKGROUND: The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression. METHODS: The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells. RESULTS: We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR. CONCLUSIONS: A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.

Immediate impact of primary surgery on health-related quality of life of hospitalized patients with oral and oropharyngeal cancer.

PURPOSE: Oral and oropharyngeal tumor resection may be associated with disfigurement and dysfunctions that affect essential domains of life. This study aimed at assessing the immediate impact of primary surgery on the health-related quality of life for these patients. PATIENTS AND METHODS: Forty-seven patients with squamous cell carcinoma of the lips, oral cavity, or oropharynx, and undergoing treatment in the head and neck surgery center of a large general hospital in the city of São Paulo, Brazil, from October 2005 to September 2006, completed the University of Washington Quality of Life questionnaire pre- and postoperatively (before hospital discharge). A paired t test evaluated differences between assessments; Poisson regression estimated ratios of ratings attributed to each domain (pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder pain, taste, saliva, mood, and anxiety) per patient stratified by sociodemographic, clinical, and behavioral characteristics. RESULTS: The immediate impact of surgery on health-related quality of life corresponded to a 31.1% reduction in the overall rating. The most affected domains were chewing (-73.5%), taste (-61.4%), swallowing (-57.3%), speech (-46.0%), and pain (-42.3%). Anxiety (+65.5%) was the sole domain that improved immediately after surgery. Comparisons involving subgroups of patients indicated that different clinical conditions (regional metastasis, tumor size, and location) were not associated with discrepant health-related quality of life immediately after surgery. CONCLUSIONS: The routine pre- and postoperative assessment of health-related quality of life may contribute to evaluate treatment effectiveness, which would otherwise rely exclusively on assessing end-point results such as survival and tumor relapse. This information is relevant to attenuate the prejudicial impact of surgery on the physical and psychosocial functioning of patients.

Oral health, hygiene practices and oral cancer

OBJETIVO: Avaliar a associação entre saúde e higiene bucal na ocorrência de câncer oral. MÉTODOS: Estudo caso-controle de base hospitalar, realizado entre 1998 e 2002 na área metropolitana de São Paulo, SP. Foram incluídos 309 pacientes com carcinoma epidermóide de boca e orofaringe e 468 controles, pareados com os casos por sexo e idade. Os casos foram levantados em sete hospitais que concentram a assistência médica a pacientes com a doença e os controles rastreados em cinco hospitais gerais dentre os sete. Informações pormenorizadas sobre tabagismo, consumo de álcool, escolaridade, saúde bucal e práticas de higiene bucal foram obtidas por entrevista. Por meio de análise de regressão logística não condicional foram calculados odds ratios (OR) e intervalos com 95 por cento de confiança (IC 95 por cento), ajustados por sexo, idade, nível educacional, tabagismo e consumo de álcool, bem como para as demais variáveis de saúde e higiene bucal. RESULTADOS: Uso de prótese bucal total não se associou a câncer oral, mas sangramento gengival freqüente apresentou alta associação (OR=3,1; IC 95 por cento: 1,2;7,9). Nunca ter consultado dentista mostrou associação com câncer oral (OR=2,5; IC 95 por cento: 1,3;4,8). Uso diário de enxaguatórios bucais apresentou associação mais intensa com tumores de faringe (OR=4,7; IC 95 por cento: 1,8;12,5) do que com tumores de boca (OR=3,2; IC 95 por cento: 1,6;6,3). CONCLUSÕES: Sangramento gengival, ausência de consultas com dentistas e uso regular de enxaguatórios bucais foram fatores associados com câncer oral, independentemente de tabagismo e consumo de bebidas alcoólicas.

Oral health, hygiene practices and oral cancer.

OBJECTIVE: To assess the association between oral health and hygiene practices and oral cancer. METHODS: Hospital-based case-control study in the metropolitan area of São Paulo, southeastern Brazil, from 1998 to 2002. A total 309 patients with squamous cell carcinoma of the mouth and the pharynx and 468 controls matched by sex and age were included in the study. Cases were recruited in seven reference hospitals and controls were selected in five out of the seven participating hospitals. Detailed information on smoking, alcohol consumption, schooling, oral health status and hygiene practices were obtained through interviews. Odds ratios (OR) and 95% confidence intervals (95% CI), adjusted by sex, age, schooling, smoking, alcohol consumption as well as the variables oral health status and hygiene practices were estimated using unconditional logistic regression analyses. RESULTS: The use of complete dental prosthesis was not associated with oral cancer but regular gum bleeding showed a strong association (OR 3.1; 95% CI 1.2-7.9). Those who never attended a dental visit were more likely to have oral cancer (OR 2.5; 95% CI 1.3-4.8). Daily mouthwash use showed a stronger association to pharynx (OR 4.7; 95% CI 1.8-12.5) than mouth cancer (OR 3.2; 95% CI 1.6-6.3). CONCLUSIONS: Gum bleeding, no dental care, and daily mouthwash use were factors associated with oral cancer regardless of tobacco and alcohol consumption.

Overexpression of Fos-related antigen-1 in head and neck squamous cell carcinoma.

The activating protein-1 (AP-1) family of transcription factors has been implicated in the control of proliferation and differentiation of keratinocytes, but its role in malignant transformation is not clear. The aim of this study is to assess the pattern of mRNA expression of jun-fos AP-1 family members in 45 samples of head and neck squamous cell carcinomas (HNSCC) and matched adjacent mucosa by means of Northern blot analysis. Transcripts of all family members were identified, except for JunB that was detected only by means of reverse transcription polymerase chain reaction. Neither c-Fos nor JunD or FosB mRNA differed between tumours and normal tissues. We observed a strong Fos-related antigen-1 (Fra-1) and Fra-2 expression, but only Fra-1 mRNA densitometric values were higher in tumour, compared to normal adjacent mucosa (t-test, P = 0.006). A direct relationship between the positive expression of Fra-1 mRNA, above tumour median, was associated with the presence of compromised lymph nodes (Fischer exact test, P = 0.006). In addition, Fra-1 protein staining was assessed in a collection of 180 tumours and 29 histologically normal samples adjacent to tumours in a tissue array. Weak reactivity, restricted to the basal cell layer, was detected in 79% of tumour adjacent normal tissues, opposed to the intense reactivity of cancer tissues. In the subgroup of oral cancers, we have observed a shift in Fra-1 immunoreactivity, as long as the number of patients in each category, cytoplasmic or nuclear/cytoplasmic staining, was analysed (Fischer exact test, P = 0.0005). Thus, Fra-1 gene induction and accumulation of Fra-1 protein may contribute to the neoplastic phenotype in HNSCC.

Paradigma da disseminação local do carcinoma epidermóide da base de língua / Paradigm of local spreading in squamous cell carcinoma of the base of the tongue

OBJETIVO: Analisar o padrão de disseminação local através da delimitação clínica da extensão da lesão primária assim como os subsítios invadidos. FORMA DE ESTUDO: Clínico retrospectivo. MATERIAL E MÉTODO: Foram analisados os prontuários de 290 pacientes com carcinoma epidermóide de base de língua no Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital Heliópolis, Hosphel, São Paulo - Brasil, de 1977 a 2000, sendo estadiados pelo TNM da UICC, e os resultados analisados pelo teste do Quiquadrado para tabelas Z x N (Cochran) para estudo da associação dos sítios e dimensão da neoplasia em relação à invasão da linha média. RESULTADOS: Com predomínio dos homens (8:1) e da 6ª década de vida (41,0 por cento), 83,8 por cento eram etilistas e tabagistas e em 4,7 por cento os hábitos estavam ausentes. Quanto aos sintomas, odinofagia (37,6 por cento), linfonodo (21,7 por cento) e a média de tempo entre o 1º sintoma e o diagnóstico de 6 meses (62,0 por cento). Quanto ao estadiamento, tivemos T1-T2 (18,3 por cento), T3 (32,4 por cento), T4(50,7 por cento). Quanto à disseminação local, em direção à valécula (25,3 por cento), epiglote (18,7 por cento), glote (2,7 por cento), anteriormente para o v lingual em (22,4 por cento) e póstero lateralmente para a prega faringloepiglótica (6,6 por cento) e seio piriforme (2,2 por cento). Quanto a ultrapassagem da linha média, isso ocorreu em 66,2 por cento dos casos, sendo 42,2 por cento (T2), 54,2 por cento (T3) e 82,9 por cento (T4). CONCLUSÃO: o carcinoma epidermóide no estádio T4 ultrapassa a linha média da base da língua em 82,9 por cento.

A novel germ-line point mutation in RET exon 8 (Gly(533)Cys) in a large kindred with familial medullary thyroid carcinoma.

Familial medullary thyroid carcinoma is related to germ-line mutations in the RET oncogene, mainly in cysteine codon 10 or 11, whereas noncysteine mutations in codons 13-15 are rare. We now report a new missense point mutation in exon 8 of the RET gene (1597G-->T) corresponding to a Gly(533)Cys substitution in the cysteine-rich domain of RET protein in 76 patients from a 6-generation Brazilian family with 229 subjects, with ascendants from Spain. It is likely that the mutation causes familial medullary thyroid carcinoma (FMTC), because no other mutation was found in RET, the mutation cosegregates with medullary thyroid carcinoma (MTC) or C cell hyperplasia (CCH) in patients subjected to surgery, and family members without the mutation are clinically unaffected. The histological analysis of 35 cases submitted to thyroidectomy revealed that 21 patients had MTC after the age of 40 yr and 8 before the age of 40 yr, 4 presented MTC or CCH before the age of 18 yr, 2 died due to MTC at the age of 53 and 60 yr, and CCH was found in a 5-yr-old child, suggesting a clinical heterogeneity. To improve the diagnosis of FMTC, analysis of exon 8 of RET should be considered in families with no identified classical RET mutations.

Estudo de variáveis demográficas, ocupacionais e co-carcinogenéticas no carcinoma espinocelular da base de língua nas mulheres / Study of demographic, ocupacional and co-carcinogenetics factors in squamous cell carcinoma of base of the tongue in women

Avaliar a relação entre carcinógenos e o carcinoma espinocelular no sexo feminino. FORMA DE ESTUDO: Retrospectivo näo randomizado. OBJETIVO: Determinar a relaçäo entre carcinógenos (álcool e fumo) e o carcinoma espinocelular no sexo feminino na base da língua. MATERIAL E MÉTODOS: Estudo retrospectivo de 31 pacientes do sexo feminino realizado no Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital Heliópolis, Hosphel, São Paulo (1977 a 2000). Foram analisados variáveis como etnia, idade, profissäo, tabagismo, etilismo, queixa principal, o intervalo de tempo entre o início da queixa e a procura do médico e o estadiamento clínico. Quanto ao tratamento estatístico, foram utilizados os Testes de Kappa e o de Mc Nemar. RESULTADOS: Houve predomínio da raça branca (58,1 por cento) sobre a negra (35,5 por cento) e a amarela (6,4 por cento), bem como da 6ª décadade vida; sendo profissionais do lar (83,9 por cento) trabalhadoras na agricultura 6,4 por cento). Indústria (3,2 por cento), comércio e liberais (3,2 por cento). Houve mais consumo isolado do tabagismo (48,4 por cento), ambos (45,2 por cento) e nenhum (6,4 por cento). Quanto à sintomatologia, odinofagia (48,4 por cento), nódulo no pescoço (19,3 por cento), disfagia (12,9 por cento); otalgia (9,7 por cento), ferida na língua (6,4 por cento) e rouquidäo (3,2 por cento). Quanto ao estadiamento, T3-4 (74,1 por cento), T1-2 (25,8 por cento), N0 (29,0 por cento), N1(29,0 por cento), N2-3 (42,0 por cento). CONCLUSÖES: O carcinoma espinocelular em mulheres predominou na 6ª década, na raça branca, tendo como principais sintomas odinofagia e linfonodo cervical metastático. Houve predomínio do tabagismo sobre o etilismo, em paciente T3-4, sendo que a maioria já portador de metástase linfonodal à 1ª consulta

[Microvascular density in carcinoma of the tongue]. / Densidade microvascular no carcinoma de língua.

BACKGROUND: Assessment of microvascular density in squamous cell carcinoma of the oral tongue (primary lesion and metastasis). METHODS: Immunohistochemical analysis by anti CD-34 of neoangiogenesis density and its relation with clinical and histological data concerning the prognosis. After optic microscopy amplification, the relation between microvascular density, clinico-histological data and prognosis, was established. RESULTS: The microvascular density presented 15.4 vessels/field (5.5 to 25.3) in primary tumors and 16.4 vessels/field (12 to 32.2) in lymph node metastases. It was observed an inverse relation between microvascular density in primary lesions and their lymph node metastasis (r= -0.68 and p=0,04). CONCLUSIONS: No evidence was detected between microvascular density, histological features and prognosis. There is an inverse relation between microvascular density in primary tumor and in lymphonode metastasis, suggesting a regional or systemic control of angiogenesis in squamous cell carcinoma of the oral tongue.

Densidade microvascular no carcinoma de língua / Microvascular density in carcinoma of the tongue

OBJETIVO: Avaliar a densidade microvascular no carcinoma epidermóide de língua oral, no sítio primário e em suas metástases linfáticas. MÉTODOS: Foram avaliados retrospectivamente 30 pacientes com carcinoma epidermóide restrito à língua oral, submetidos a tratamento cirúrgico incluindo esvaziamento cervical. A densidade microvascular foi avaliada por imunohistoquímica empregando o anticorpo anti-CD34 e quantificada à microscopia óptica, no tumor primário e em suas metástases linfonodais. Foi avaliada a relaçäo entre a densidade microvascular, as variáveis clínicas e histológicas e o prognóstico. RESULTADOS: A densidade microvascular apresentou mediana de 15,4 vasos/campo (5,5 a 25,3) nos tumores primários e 16,4 vasos/campo (12 a 32,2) nas metástases linfáticas. Foi observada uma relaçäo inversa entre a densidade microvascular no tumor primário e na respectiva metástase linfática (r= -0,68 e p=0,04). A densidade microvascular näo apresentou relaçäo com outras variáveis histológicas ou com o prognóstico. CONCLUSÄO: Há Uma relaçäo inversa entre a densidade microvascular no sítio primário e na metástase linfonodal, sugerindo um controle regional ou sistêmico da angiogênese

Metastatizaçäo linfática oculta no carcinoma epidermóide das vias aerodigestivas superiores / Occult lymphatic metastatization in squamous cell carcinoma of head neck

Introduçäo: Os esvaziamentos cervicais eletivos säo procedimentos para identificar metástases cervicais ocultas em câncer de cabeça e pescoço. Forma de Estudo: Clínico retrospectivo. Objetivo: Avaliar a metastatizaçäo linfática oculta em pacientes com carcinoma epidermóide das vias aero-digestivas superiores. Material e Método: Foram avaliados, retrospectivamente 428 pacientes submetidos a esvaziamento cervical eletivo entre os anos de 1977 e 1996. Foi analisada a incidência de casos falsos-negativos (pN+) e sua relaçäo com o tamanho (estádio T) e sítio anatômico do tumor primário, graduaçäo histológica, sexo e faixa etária. Também foram avaliadas as cadeias linfonodais. Resultados: Metástases linfonodais ocultas foram diagnosticadas em 32 por cento dos pacientes, sendo 26 por cento nos tumores de laringe, 31 por cento na orofaringe, 36 por cento na cavidade oral e 40 por cento na hipofaringe. Houve preponderância de metástases nos níveis II e III. Apenas os tumores de cavidade oral apresentaram metastatizaçäo significativa para o nível I (14 por cento). As metástases ocultas acometeram um linfonodo em 14 por cento e vários em 18 por cento dos pacientes. O estadiamento T se relacionou com a metastatizaçäo oculta apenas nos tumores de laringe. Conclusöes: Os níveis linfáticos II e III foram os mais afetados para as lesöes da faringe e laringe, e o nível I para a cavidade oral, enquanto que os fatores de risco (idade, sexo e o grau de diferenciaçäo histológica) näo foram determinantes significativos de metástases ocultas

Prognostic significance of microscopic and macroscopic extracapsular spread from metastatic tumor in the cervical lymph nodes.

It has been established that the presence or absence of cervical node metastases in patients with head and neck squamous cell carcinoma (HNSCC) is a powerful prognostic indicator. This report reviews the evolution of thinking over the past 70 years with regard to the import and detection of cervical nodal metastases which exhibit spread of tumor beyond the confines of the original encompassing nodal capsule. In the process, this discussion touches upon clinical examination, gross and microscopic pathologic examination, and radiographic imaging studies. In particular, the distinction between gross nodal extracapsular spread of tumor and microscopic nodal extracapsular spread of tumor has been drawn in recent reports; this raises the possibility that identification of microscopic breaching of the nodc capsule by tumor might provide clinically significant information which is not provided by the gross observation of an intact lymph node capsule. While it remains to be seen whether microscopic extracapsular spread alone will prove to be an important prognostic factor, it is recommended that selective neck dissection continue to be offered even in those patients with clinically negative necks; further studies should aid in defining the import of microscopic extracapsular tumor spread in patients with positive cervical nodes.

Correlação clínico-patológica entre a presença da necrose microscópica e a revolução da carcinoma epidermóide inicial da laringe / Clinical-pathologic correlation between the presence of microscopic necrosis and evolution of initial laryngeal squamous cell carcinoma

Introdução: Fazer a análise da presença da necrose tumoral microscópica no tumor primário inicial da laringe e correlacioná-la com algumas características clínicas e histopatológicas, objetivando identificar seu impacto na evolução. Forma de estudo: Retrospectivo clínico. Material e métodos: Estudo retrospectivo das fichas médicas e revisão dos cortes histológicos obtidos de 49 casos de carcinomas epidermóides da laringe, estadiados como T1 e T2, tratados no Serviço de Cirurgia de Cabeça e Pescoço do Complexo Hospitalar Heliópolis, de São Paulo/ SP, entre janeiro/1978 e dezembro/1997. Resultados: Houve forte associação entre a presença de necrose microscópica e a característica infiltrativa da lesão primária (p=0,004), lesões na supraglote (p=0,021), estádio clínico T2 (p=0,04), ocorrência de metástase cervical (p=0,04) e lesões menos diferenciadas (p=0,025). Aqueles casos que apresentaram necrose microscópica tenderam à melhor evolução. Conclusão: As informações obtidas do nosso estudo sugerem que a necrose por si, como classificada por técnicas histopatológicas, pode não ter influência exclusiva ou reflexo no crescimento volumétrico, refletindo a taxa de crescimento tumoral, mas pode estar relacionada a outros fatores tumorais e/ou do hospedeiro como a morte celular programada.

Correlaçäo clínico-epidemiológica do carcinoma epidermóide (T1 e T2) da laringe: estudo de 73 casos / Clinical and epidemiological correlation of initial laryngeal squamous cells carcinoma (T1 and T2): study of 73 cases

As modificações funcionais e estruturais causadas pelo câncer na laringe estão bem estabelecidas e reconhecidas. Porém, os erros na avaliação da laringe do paciente não são infrequêntes. Esses erros são tanto de incorreta interpretação de sinais e sintomas quanto o não reconhecimento de alterações anatômicas visíveis na propedêutica armada. Por considerar escassos os trabalhos apresentados na literatura que tratam da relação dos dados clínicos e a epidemiologia do câncer de laringe, propusemo-nos a analisar e correlacionar algumas variáveis clínicas e epidemiológicas, com objetivo de uma melhor compreensão da história natural e formas de apresentação do câncer laríngeo. Forma do estudo: Clínico retrospectivo. Método: Estudo retrospectivo a partir da análise dos prontuários de 73 pacientes portadores de carcinoma epidermóide inicial da laringe (T1 e T2), virgens de tratamento e submetidos à cirurgia no Serviço de Cirurgia de Cabeça e Pescoço do Hospital Heliópolis /SP, no período de setembro/1977 a dezembro /1997. Resultados: Encontramos predomínio de pacientes do sexo masculino, entre a sexta e a sétima décadas de vida, tabagistas e etilistas, com tumores glóticos. Para aqueles portadores de lesão glótica o sintoma predominante foi a disfonia; já para os pacientes com tumores supraglóticos, sintomas relacionados à via digestiva preponderaram. Em relação à característica macroscópica, as lesões na glote eram preferencialmente vegetantes, enquanto que na supraglote eram infiltrativas. Conclusões: A evolução clínica do câncer laríngeo é uma reprodução fiel da progressão tumoral dentro da região acometida, com sintomas distintos para os diferentes sítios. Assim, sua manifestação é bem representativa da alteração morfológica provocada no órgão