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Supplementary Data from Gene Expression Profiling of Papillary Thyroid Carcinoma Identifies Transcripts Correlated with BRAF Mutational Status and Lymph Node Metastasis

Purpose: To identify papillary thyroid carcinoma (PTC)–associated transcripts, we compared the gene expression profiles of three Serial Analysis of Gene Expression libraries generated from thyroid tumors and a normal thyroid tissue.Experimental Design: Selected transcripts were validated in a panel of 57 thyroid tumors using quantitative PCR (qPCR). An independent set of 71 paraffin-embedded sections was used for validation using immunohistochemical analysis. To determine if PTC-associated gene expression could predict lymph node involvement, a separate cohort of 130 primary PTC (54 metastatic and 76 nonmetastatic) was investigated. The BRAFV600E mutational status was compared with qPCR data to identify genes that might be regulated by abnormal BRAF/MEK/extracellular signal-regulated kinase signaling.Results: We identified and validated new PTC-associated transcripts. Three genes (CST6, CXCL14, and DHRS3) are strongly associated with PTC. Immunohistochemical analysis of CXCL14 confirmed the qPCR data and showed protein expression in PTC epithelial cells. We also observed that CST6, CXCL14, DHRS3, and SPP1 were associated with PTC lymph node metastasis, with CST6, CXCL14, and SPP1 being positively correlated with metastasis and DHRS3 being negatively correlated. Finally, we found a strong correlation between CST6 and CXCL14 expression and BRAFV600E mutational status, suggesting that these genes may be induced subsequently to BRAF activation and therefore may be downstream in the BRAF/MEK/extracellular signal-regulated kinase signaling pathway.Conclusion:CST6, CXCL14, DHRS3, and SPP1 may play a role in PTC pathogenesis and progression and are possible molecular targets for PTC therapy.

OBJECTIVE: As a lifestyle-related disease, social and cultural disparities may influence the features of squamous cell carcinoma of the head and neck in different geographic regions. We describe demographic, clinical, and pathological aspects of squamous cell carcinoma of the head and neck according to the smoking and alcohol consumption habits of patients in a Brazilian cohort. METHODS: We prospectively analyzed the smoking and alcohol consumption habits of 1,633 patients enrolled in five São Paulo hospitals that participated in the Brazilian Head and Neck Genome Project – Gencapo. RESULTS: The patients who smoked and drank were younger, and those who smoked were leaner than the other patients, regardless of alcohol consumption. The non-smokers/non-drinkers were typically elderly white females who had more differentiated oral cavity cancers and fewer first-degree relatives who smoked. The patients who drank presented significantly more frequent nodal metastasis, and those who smoked presented less-differentiated tumors. CONCLUSIONS: The patients with squamous cell carcinoma of the head and neck demonstrated demographic, clinical, and pathological features that were markedly different according to their smoking and drinking habits. A subset of elderly females who had oral cavity cancer and had never smoked or consumed alcohol was notable. Alcohol consumption seemed to be related to nodal metastasis, whereas smoking correlated with the degree of differentiation.

Recent systematic reviews concluded that the frequent consumption of fruits and vegetables is inversely associated with the risk of oral cancer. We assessed this association, specifically comparing results obtained to nonsmokers and smokers, as well to nondrinkers and drinkers. We conducted a case-control study involving 296 patients with oral squamous cell carcinoma (cases) attended in 3 major hospitals of São Paulo, Brazil, paired with 296 controls, recruited from outpatient units of the same hospitals. Multivariate models assessed the effect of fruits and salads according to smoking and drinking. The intake of fruit was associated with the prevention of the disease in the specific assessment among light [odds ratio (OR) = 0.46; 95% confidence interval (CI) = 0.27-0.78) and heavy (OR = 0.30; 95% CI = 0.14-0.65) smokers. The same was observed for vegetables consumption. For nonsmokers, no fruit (OR = 50; 95% CI = 0.22-1.12) or vegetable (for tomato, OR = 0.53; 95% CI = 0.31-0.93) was associated with reduced risk of oral and oropharyngeal cancer. Similar results were found in the stratified analysis according to drinking status with OR = 0.51 (95% CI = 0.30-0.87) and 0.18 for fruits (95% CI = 0.07-0.45), respectively, for light and heavy drinkers. This observation suggests that the protective effect of fruit and salad intake may modulate the deleterious effects from tobacco and alcohol.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:26:26Z No. of bitstreams: 0 Made available in DSpace on 2014-05-27T11:26:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-04-01 The search for molecular markers to improve diagnosis, individualize treatment and predict behavior of tumors has been the focus of several studies. This study aimed to analyze homeobox gene expression profile in oral squamous cell carcinoma (OSCC) as well as to investigate whether some of these genes are relevant molecular markers of prognosis and/or tumor aggressiveness. Homeobox gene expression levels were assessed by microarrays and qRT-PCR in OSCC tissues and adjacent non-cancerous matched tissues (margin), as well as in OSCC cell lines. Analysis of microarray data revealed the expression of 147 homeobox genes, including one set of six at least 2-fold up-regulated, and another set of 34 at least 2-fold down-regulated homeobox genes in OSCC. After qRT-PCR assays, the three most up-regulated homeobox genes (HOXA5, HOXD10 and HOXD11) revealed higher and statistically significant expression levels in OSCC samples when compared to margins. Patients presenting lower expression of HOXA5 had poorer prognosis compared to those with higher expression (P=0.03). Additionally, the status of HOXA5, HOXD10 and HOXD11 expression levels in OSCC cell lines also showed a significant up-regulation when compared to normal oral keratinocytes. Results confirm the presence of three significantly upregulated (>4-fold) homeobox genes (HOXA5, HOXD10 and HOXD11) in OSCC that may play a significant role in the pathogenesis of these tumors. Moreover, since lower levels of HOXA5 predict poor prognosis, this gene may be a novel candidate for development of therapeutic strategies in OSCC. Department of Oral Pathology School of Dentistry University of São Paulo, Av. Prof. Lineu Prestes 2227, Cidade Universitária, 05508-000 São Paulo Department of Head and Neck Surgery School of Medicine University of São Paulo, Av. Dr. Arnaldo 455, Cerqueira César, 01246903 São Paulo Head and Neck Surgery Division Heliópolis Hospital Complex, Rua Cônego Xavier 276, Sacomã, 04231-030 São Paulo Department of Head and Neck Surgery Arnaldo Vieira de Carvalho Cancer Institute, Rua Dr Cesário Motta Junior 112, Vila Buarque, 01221020 São Paulo Department of Molecular Biology São José do Rio Preto School of Medicine, Av. Brigadeiro Faria Lima 5416-Vila São Pedro, 15090-000 São José do Rio Preto Department of Genetics and Evolutionary Biology Institute of Biosciences University of São Paulo, R. do Matão, travessa 14 321, Cidade Universitária, 05508-090 São Paulo Department of Genetics Biosciences Institute University of São Paulo, Rua do Matão, trav. 14 321, Cidade Universitária, 05508-090 São Paulo School of Medicine USP, São Paulo Albert Einstein Jewish Teaching and Research Institute (IIEP), São Paulo School of Medicine of São José do Rio Preto São José Dos Campos Dental School UNESP Cancer Institute Arnaldo Vieira de Carvalho, São Paulo School of Dentistry USP, São Paulo Heliópolis Hospital, São Paulo School of Medicine of Ribeirão Preto USP School of Public Health USP, São Paulo University of Vale do Paraíba, São José dos Campos School of Medicine UNIFESP, São Paulo Faculty of Pharmaceutical Sciences of Ribeirão Preto USP, SP São José Dos Campos Dental School UNESP

To examine whether denture use and recurrent sores caused by ill-fitting dentures are associated with intra-oral squamous cell carcinoma (IO-SCC) in individuals exposed to tobacco.We conducted a hospital-based case-control study. The study population 124 patients wi th IO-SCC and the same number of controls (individually paired according to gender and age) recruited from outpatient units of the same hospital. Conditional logistic regression analysis assessed the effect of denture use and recurrent oral sores by ill-fitting dentures, adjusted by covariates on the lifetime exposure to alcohol and tobacco, socioeconomic standings, and dietary patterns.The use of dentures showed no association with IO-SCC [adjusted odds ratio (OR) 1.40, 95 percent confidence interval 0.51-3.87, P = 0.513] in an assessment controlled by socioeconomic position, lifetime exposure to alcohol and tobacco, and dietary patterns. However, the report of recurrent sores caused by ill-fitting dentures showed significant association with the disease (adjusted OR 4.58, 95 percent confidence interval 1.52-13.76, P = 0.007).The association between recurrent oral sores caused by ill-fitting dentures and squamous cell carcinoma of the mouth in smokers is in agreement with the hypothesis that the chronic physical irritation of oral mucosa contributes to the topical carcinogenic effect of tobacco, which must be taken into careful consideration in the planning of dental services for adults and the elderly.

Purpose: To identify papillary thyroid carcinoma (PTC)–associated transcripts, we compared the gene expression profiles of three Serial Analysis of Gene Expression libraries generated from thyroid tumors and a normal thyroid tissue. Experimental Design: Selected transcripts were validated in a panel of 57 thyroid tumors using quantitative PCR (qPCR). An independent set of 71 paraffin-embedded sections was used for validation using immunohistochemical analysis. To determine if PTC-associated gene expression could predict lymph node involvement, a separate cohort of 130 primary PTC (54 metastatic and 76 nonmetastatic) was investigated. The BRAFV600E mutational status was compared with qPCR data to identify genes that might be regulated by abnormal BRAF/MEK/extracellular signal-regulated kinase signaling. Results: We identified and validated new PTC-associated transcripts. Three genes (CST6, CXCL14, and DHRS3) are strongly associated with PTC. Immunohistochemical analysis of CXCL14 confirmed the qPCR data and showed protein expression in PTC epithelial cells. We also observed that CST6, CXCL14, DHRS3, and SPP1 were associated with PTC lymph node metastasis, with CST6, CXCL14, and SPP1 being positively correlated with metastasis and DHRS3 being negatively correlated. Finally, we found a strong correlation between CST6 and CXCL14 expression and BRAFV600E mutational status, suggesting that these genes may be induced subsequently to BRAF activation and therefore may be downstream in the BRAF/MEK/extracellular signal-regulated kinase signaling pathway. Conclusion: CST6, CXCL14, DHRS3, and SPP1 may play a role in PTC pathogenesis and progression and are possible molecular targets for PTC therapy.

Biomarkers of papillary thyroid carcinoma (PTC) metastasis can accurately identify metastatic cells and aggressive tumor behavior. To find new markers, serial analysis of gene expression (SAGE) was done on three samples from the same patient: normal thyroid tissue, primary PTC, and a PTC lymph node metastasis. This genomewide expression analysis identified 31 genes expressed in lymph node metastasis, but not in the primary tumor. Eleven genes were evaluated by quantitative real-time reverse transcription-PCR (qPCR) on independent sets of matched samples to find genes that were consistently different between the tumor and metastatic samples. LIMD2 and PTPRC (CD45) showed a statistically significant difference in expression between tumor and metastatic samples (P < 0.0045), and an additional gene (LTB) had borderline significance. PTPRC and LTB were tested by immunohistochemistry in an independent set of paired samples, with both markers showing a difference in protein expression. All 20 metastases from 6 patients showed expression in both markers, with little or no expression in primary tumor. Some of these markers could provide an improved means to detect metastatic PTC cells during initial staging of a newly diagnosed carcinoma and/or to rule out recurrence. The functional role of these genes may also provide insight into mechanisms of thyroid cancer metastasis. [Cancer Res 2007;67(16):7885–92]

We determined whether resveratrol, a phenolic antioxidant found in grapes and other food products, inhibited phorbol ester (PMA)-mediated induction of COX-2 in human mammary and oral epithelial cells. Treatment of cells with PMA induces COX-2 and causes a marked increase in the production of prostaglandin E2. These effects were inhibited by resveratrol. Resveratrol suppressed PMA-mediated increases in COX-2 mRNA and protein. Nuclear run-offs revealed increased rates of COX-2 transcription after treatment with PMA, an effect that was inhibited by resveratrol. PMA caused about a 6-fold increase in COX-2 promoter activity, which was suppressed by resveratrol. Transient transfections utilizing COX-2 promoter deletion constructs and COX-2 promoter constructs, in which specific enhancer elements were mutagenized, indicated that the effects of PMA and resveratrol were mediated via a cyclic AMP response element. Resveratrol inhibited PMA-mediated activation of protein kinase C. Overexpressing protein kinase C-alpha, ERK1, and c-Jun led to 4.7-, 5.1-, and 4-fold increases in COX-2 promoter activity, respectively. These effects also were inhibited by resveratrol. Resveratrol blocked PMA-dependent activation of AP-1-mediated gene expression. In addition to the above effects on gene expression, we found that resveratrol also directly inhibited the activity of COX-2. These data are likely to be important for understanding the anti-cancer and anti-inflammatory properties of resveratrol.

Background: The role of human papillomavirus (HPV) on head and neck squamous cell carcinoma (HNSCC) survival in regions with low HPV prevalence is not yet clear. We evaluated the HPV16 infection on survival of HNSCC Brazilian patient series. Methods: This cohort comprised 1,093 HNSCC cases recruited from 1998 to 2008 in four Brazilian cities and followed up until June 2009. HPV16 antibodies were analyzed by multiplex Luminex assay. In a subset of 398 fresh frozen or paraffin blocks of HNSCC specimens, we analyzed for HPV16 DNA by L1 generic primer polymerase chain reaction. HNSCC survival according to HPV16 antibodies was evaluated through Kaplan-Meier method and Cox regression. Results: Prevalence of HPV16 E6 and E6/E7 antibodies was higher in oropharyngeal cancer than in other head and neck tumor sites. HPV16 DNA positive in tumor tissue was also higher in the oropharynx. Seropositivity for HPV16 E6 antibodies was correlated with improved HNSCC survival and oropharyngeal cancer. The presence of HPV16 E6/E7 antibodies was correlated with improved HNSCC survival and oropharyngeal cancer survival. The death risk of oropharyngeal squamous cell carcinoma patients HPV16 E6/E7 antibodies positive was 78 % lower than to those who test negative. Conclusion: Oropharyngeal squamous cell carcinoma is less aggressive in the HPV16 E6/E7 positive serology patients. HPV16 E6/E7 antibody is a clinically sensible surrogate prognostic marker of oropharyngeal squamous cell carcinoma. © 2014 Springer International Publishing.

Wyss, Annah Hashibe, Mia Chuang, Shu-Chun Lee, Yuan-Chin Amy Zhang, Zuo-Feng Yu, Guo-Pei Winn, Deborah M Wei, Qingyi Talamini, Renato Szeszenia-Dabrowska, Neonila Sturgis, Erich M Smith, Elaine Shangina, Oxana Schwartz, Stephen M Schantz, Stimson Rudnai, Peter Purdue, Mark P Eluf-Neto, Jose Muscat, Joshua Morgenstern, Hal Michaluart, Pedro Jr Menezes, Ana Matos, Elena Mates, Ioan Nicolae Lissowska, Jolanta Levi, Fabio Lazarus, Philip La Vecchia, Carlo Koifman, Sergio Herrero, Rolando Hayes, Richard B Franceschi, Silvia Wunsch-Filho, Victor Fernandez, Leticia Fabianova, Eleonora Daudt, Alexander W Dal Maso, Luigino Curado, Maria Paula Chen, Chu Castellsague, Xavier de Carvalho, Marcos Brasilino Cadoni, Gabriella Boccia, Stefania Brennan, Paul Boffetta, Paolo Olshan, Andrew F eng R03 CA113157/CA/NCI NIH HHS/ R24 HD041025/HD/NICHD NIH HHS/ T32-CA09330/CA/NCI NIH HHS/ T32ES007018/ES/NIEHS NIH HHS/ Meta-Analysis Research Support, N.I.H., Extramural 2013/07/03 06:00 Am J Epidemiol. 2013 Sep 1;178(5):679-90. doi: 10.1093/aje/kwt029. Epub 2013 Jun 30.; International audience; Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend

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.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.Seventeen of the 18 genes showed statistical significance based on a mean relative level of expression (P0.05). KLK1 (sensitivity = 0.97) and PVALB (sensitivity = 0.94) were the best candidate markers. The combination of PVALB and C1orf24 increased specificity to97% and maintained sensitivity for detection of carcinoma.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.

Made available in DSpace on 2013-08-28T14:07:40Z (GMT). No. of bitstreams: 1 WOS000278383600001.pdf: 960234 bytes, checksum: 9cd26a9750ec13e67eaf9019e1f48e7b (MD5) Made available in DSpace on 2013-09-30T18:12:07Z (GMT). No. of bitstreams: 2 WOS000278383600001.pdf: 960234 bytes, checksum: 9cd26a9750ec13e67eaf9019e1f48e7b (MD5) WOS000278383600001.pdf.txt: 69473 bytes, checksum: e718db9d53c8e8829f735f82524e401f (MD5) Previous issue date: 2010-05-04 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:00:48Z No. of bitstreams: 2 WOS000278383600001.pdf: 960234 bytes, checksum: 9cd26a9750ec13e67eaf9019e1f48e7b (MD5) WOS000278383600001.pdf.txt: 69473 bytes, checksum: e718db9d53c8e8829f735f82524e401f (MD5) Made available in DSpace on 2014-05-20T14:00:48Z (GMT). No. of bitstreams: 2 WOS000278383600001.pdf: 960234 bytes, checksum: 9cd26a9750ec13e67eaf9019e1f48e7b (MD5) WOS000278383600001.pdf.txt: 69473 bytes, checksum: e718db9d53c8e8829f735f82524e401f (MD5) Previous issue date: 2010-05-04 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Rede Proteoma do Estado de São Paulo Ludwig Institute for Cancer Research Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 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. Sch Med FAMERP, Dept Mol Biol, Sao Jose do Rio Preto, Brazil São Paulo State Univ UNESP, IBILCE, Dept Biol, Sao Jose do Rio Preto, Brazil Sch Med FAMERP, Dept Otorhinolaryngol & Head & Neck Surg, Sao Jose do Rio Preto, Brazil Univ São Paulo, Inst Biociencias, Dept Genet & Evolutionary Biol, São Paulo, Brazil Arnaldo Vieira de Carvalho Hosp, Dept Head & Neck Surg, São Paulo, Brazil Univ São Paulo, Sch Med, Dept Surg, Div Head & Neck Surg, BR-09500900 São Paulo, Brazil Heliopolis Hosp, Dept Head & Neck Surg, São Paulo, Brazil UNESP, Fac Engn Ilha Solteria, Dept Biol & Zootechny, Ilha Solteira, Brazil São Paulo State Univ UNESP, IBILCE, Dept Biol, Sao Jose do Rio Preto, Brazil UNESP, Fac Engn Ilha Solteria, Dept Biol & Zootechny, Ilha Solteira, Brazil FAPESP: 04/12054-9 FAPESP: 06/60162-0 FAPESP: 04/14846-0 FINEP: 01.07.0290.00

DNA-hsp65, a DNA vaccine encoding the 65-kDa heat-shock protein of Mycobacterium leprae (Hsp65) is capable of inducing the reduction of established tumors in mouse models. We conducted a phase I clinical trial of DNA-hsp65 in patients with advanced head and neck carcinoma. In this article, we report on the vaccine's potential to induce immune responses to Hsp65 and to its human homologue, Hsp60, in these patients. Twenty-one patients with unresectable squamous cell carcinoma of the head and neck received three doses of 150, 400 or 600 microg naked DNA-hsp65 plasmid by ultrasound-guided intratumoral injection. Vaccination did not increase levels of circulating anti-hsp65 IgG or IgM antibody, or lead to detectable Hsp65-specific cell proliferation or interferon-gamma (IFN-gamma) production by blood mononuclear cells. Frequency of antigen-induced IL-10-producing cells increased after vaccination in 4 of 13 patients analyzed. Five patients showed disease stability or regression following immunization; however, we were unable to detect significant differences between these patients and those with disease progression using these parameters. There was also no increase in antibody or IFN-gamma responses to human Hsp60 in these patients. Our results suggest that although DNA-hsp65 was able to induce some degree of immunostimulation with no evidence of pathological autoimmunity, we were unable to differentiate between patients with different clinical outcomes based on the parameters measured. Future studies should focus on characterizing more reliable correlations between immune response parameters and clinical outcome that may be used as predictors of vaccine success in immunosuppressed individuals.

Considering that mycobacterial heat-shock protein 65 (hsp65) gene transfer can elicit a profound antitumoral effect, this study aimed to establish the safety, maximum-tolerated dose (MTD) and preliminary efficacy of DNA-hsp65 immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). For this purpose, 21 patients with unresectable and recurrent HNSCC were studied. Each patient received three ultrasound-guided injections at 21-day intervals of: 150, 600 or 400 microg of DNA-hsp65. Toxicity was graded according to CTCAE directions. Tumor volume was measured before and after treatment using computed tomography scan. The evaluation included tumor mass variation, delayed-type hypersensitivity response and spontaneous peripheral blood mononuclear cell proliferation before and after treatment. The MTD was 400 microg per dose. DNA-hsp65 immunotherapy was well tolerated with moderate pain, edema and infections as the most frequent adverse effects. None of the patients showed clinical or laboratory alterations compatible with autoimmune reactions. Partial response was observed in 4 out of 14 patients who completed treatment, 2 of which are still alive more than 3 years after the completion of the trial. Therefore, DNA-hsp65 immunotherapy is a feasible and safe approach at the dose of 400 microg per injection in patients with HNSCC refractory to standard treatment. Further studies in a larger number of patients are needed to confirm the efficacy of this novel strategy.

Total thyroidectomy (TT) with level VI and VII central neck dissection is the initial treatment for medullary thyroid carcinoma (MTC) without identifiable neck metastasis. Level II to V lateral neck dissection is performed if neck metastasis is present or suspected. We conducted this study to identify the frequency and clinical determinants of skip neck metastasis in MTC.We reviewed the medical records of 32 patients who underwent TT and bilateral neck dissection for MTC. The clinical features were correlated with pN status in the central versus lateral compartments of the neck.Neck lymph node metastasis (pN+) was found in 20 patients (62.5%) and skip metastases were found in 7 (35%) patients. The sensitivity of the pN status of the central compartment of the neck to predict the pN status of the lateral compartment of the neck was 53.8% and specificity was 63.2%. We found pN+ in 90% of the patients with lymph nodes15 mm in diameter versus 50% in those with lymph nodes15 mm in diameter.There is skip metastasis in MTC. It is unsafe to use the lymph node status of the central compartment of the neck to define the pN status of the lateral neck. A lymph node greater than 15 mm in diameter is related to pN status.

Univ Fed Sao Paulo, Dept Med, Div Endocrinol, Mol Endocrinol Lab, BR-04039032 Sao Paulo, Brazil

Cyclooxygenases (COX)1 catalyze the synthesis of prostaglandins (PGs) from arachidonic acid. There are two isoforms of COX, designated COX-1 and COX-2. COX-1 is expressed constitutively in most tissues and appears to be responsible for housekeeping functions1. In contrast, COX-2 is undetectable in most normal tissues but is induced by growth factors, oncogenes, carcinogens and tumor promoters2–4.

Parathyroid carcinoma is rare and represents 0.1% to 5% of the cases of hyperparathyroidism. New accounts are important to the understanding of these tumors. Experience in 9 cases is reported.From 1970 to 1995, 10 patients with parathyroid carcinoma demonstrated by clinical course or pathologic features of malignancy were treated. The patient's clinical data, laboratory and imaging examinations, surgical findings, pathology, recurrences, and survival were analyzed.One male patient was excluded because of insufficient data. Average age was 51 years, with female:male ratio of 2:1. Average calcium level was 14,3 mg/dL. Palpable mass was found in 55%, bone disease in 89%, and renal disease in 78%. Four patients were reoperations. Five were operated on for hyperparathyroidism (1/tertiary). Capsular invasion was the most incident pathologic feature. Local recurrence occurred in 55%; neck node and bone metastasis in 11%, and lung in 33%. Two patients are alive and 5 died of disease.Parathyroid carcinoma has clinical and laboratory features that can help diagnosis at the first surgery. It seems to have variable malignancy.

Tobacco smoking is a major risk factor for head and neck cancer (HNC). Family history of cancer is also associated with HNC. This association lies in the difficulty in balancing the influence of hereditary vs shared environmental factors. We aimed to assess the role of smoking status of affected relatives on the risk of HNC. This study comprised 567 patients with HNC and 328 controls without cancer admitted in five centers in Sao Paulo State, Brazil, from 2005 to 2009; all of them had at least one parent or sibling with cancer of any site reported. Multivariate unconditional logistic regression was used to assess the effect of tobacco smoking in affected relatives on the risk of HNC. ORs were adjusted on socioeconomic status, tobacco smoking, alcohol drinking, age, sex and the number of relatives that experienced cancer. Having one or more smoker affected relative was associated with a higher risk of HNC (OR=2.39; 95% CI 1.69 to 3.37). This association remained high when stratification by cancer subsites was performed: oral cavity (2.11; 1.41 to 3.17), oropharynx (2.84; 1.54 to 5.23), larynx (4.05; 2.36 to 6.93). In conclusion, cancer affected relatives of HNC cases are more exposed to tobacco smoking than cancer affected relatives of controls. This finding suggests that lifestyle factors of parents or siblings with cancer history may play a role on the association between family history of cancer and HNC.

Introdução. O Papilomavírus humano (HPV), particularmente o tipo 16, têm sido associado com risco e prognóstico de tumores de cabeça e pescoço. Contudo, o papel do DNA do HPV e resposta sorológica na sobrevida neste grupo de pacientes ainda não está claro. Objetivos. Avaliar o efeito do HPV (resposta sorológica e detecção do DNA no tecido tumoral) na sobrevida de pacientes com carcinoma epidermóide de cabeça e pescoço, considerando-se as distintas localizações anatômicas (cavidade oral, orofaringe, hipofaringe e laringe). Material e métodos. Coorte de 1.475 pacientes com carcinoma epidermóide de cabeça e pescoço, oriundos de dois estudos multicêntricos, diagnosticados entre novembro de 1998 e dezembro de 2008 e acompanhados até 30 de junho de 2009. Detecção de DNA do HPV no tecido tumoral foi feita pela técnica de PCR (Polymerase Chain Reaction) em tecido fresco e material parafinado. Resposta sorológica às proteínas do HPV foi determinada pela técnica Multiplex Luminex. Sobrevida global e específica pela doença foram calculadas pelo método atuarial (tábuas de vida). Curvas de sobrevida de Kaplan-Meier e teste Log-rank para comparação de curvas de sobrevida foram calculados. Hazard ratio (HR) do efeito da infecção pelo HPV nos tumores de cabeça e pescoço e respectivo intervalo com 95 por cento de confiança (IC95 por cento ) foram calculados via modelo de regressão de Cox ajustado pelas variáveis: estudo de origem dos casos, sexo, idade, educação, consumo de tabaco e de álcool, estadiamento do tumor e tratamento, assim como hábitos sexuais para a subcoorte com esta informação. Resultados. Prevalência de DNA do HPV 16 no tecido tumoral foi de 6,7 por cento nos casos recentes (2003-2008) comparado com 1 por cento nos casos iniciais (1998-2002) para a subcoorte de São Paulo. Aumento da soropositividade para HPV 16 E7 nos casos do estudo mais recente (2003-2008) comparado com os casos do estudo inicial (1998-2002) resultou estatisticamente significante. Foi observada pobre concordância entre os resultados de sorologia e DNA do HPV. Pacientes mais jovens (50 anos), que não fumavam e com tumores de orofaringe apresentaram risco aumentado na resposta sorológica à proteína E6 do HPV 16. Prática de sexo oral associou-se com resposta sorológica conjunta às proteínas E6 e E7 do HPV 16. Pacientes soropositivos para HPV 16 E6 apresentaram maior sobrevida global (HR=0,62; IC95 por cento =0,44-0,87), adicionalmente observou-se que a resposta sorológica conjunta às proteínas E6 e E7 do HPV incrementou a sobrevida dos pacientes com tumores de cabeça e pescoço (HR=0,34; IC95 por cento 0,17-0,70) e de orofaringe (HR=0,17; IC95 por cento 0,05-0,59). Conclusões. A prevalência da infecção pelo HPV entre pacientes com tumores de cabeça e pescoço aumentou no período estudado. O estudo sugere que resposta sorológica conjunta às proteínas E6 e E7 do HPV 16 pode estar associada com maior sobrevida global nos tumores de cabeça e pescoço, especificamente nos pacientes com tumores de orofaringe Introduction. Human papillomavirus (HPV), especially type 16, had been associated with risk and prognostic of head and neck cancer. However, the role of HPV DNA and serological response in survival of patients with head and neck cancer is not yet clear. Objectives. Evaluate the effect of HPV (serological response and HPV DNA tumor status) in survival of patients with squamous cell carcinoma of head and neck (SCCHN), according to anatomical sites (oral cavity, oropharynx, hypopharynx and larynx). Material and methods. Cohort of 1,475 patients with SCCHN, from two multicentre studies diagnosed between November 1998 and December 2008 and followed-up until 30 of June 2009. HPV DNA detection was evaluated by PCR (Polymerase Chain Reaction) in fresh tissue and paraffin blocks. Antibodies to HPV in the serum were determinated by Multiplex Luminex technique. Overall and disease specific survival were calculated by actuarial method. Kaplan-Meier survival curves and Log-rank test in order to compare survival curves were calculated. Hazard ratio (HR) and 95 per cent of interval confidence (95 per cent IC) for Cox model regression were used to evaluate the effect of HPV infection in SCCHN, adjusted by variables: study group, sociodemographics, tobacco and alcohol consumption, tumor clinical stage and treatment, and also sexual habits in the subcohort with available information. Results. HPV DNA 16 tumoral status prevalence was 6.7 per cent in recent cases (2003-2008) compared to 1 per cent in old cases (1998-2002), only for subcohort of São Paulo. Seropositivity to HPV 16 E7 increased in the late cases (2003-2008) compared to old cases (1998-2002) and was statistically significant. Poor concordance was showed between DNA HPV and serological response to HPV. Younger patients (50 years old), no smokers and with oropharyngeal tumors showed increased risk to HPV 16 E6 serological response. Oral sex was associated with HPV 16 E6 and E7 simultaneously. Seropositivity to HPV 16 E6 had longer overall survival (HR=0.62; 95 per cent CI=0.440.87), additionally HPV 16 E6 and E7 serological response increased the survival of head and neck cancers (HR=0.34; 95 per cent CI 0.17-0.70) and oropharyngeal cancer (HR=0.17; 95 per cent CI 0.05-0.59) Conclusions. Prevalence of HPV infection in patients with SCCHN had increased in the study period. The study suggests that HPV 16 E6 serological response could be associated with increased overall survival in patients with SCCHN tumors and specifically with oropharyngeal cancer

Introdução: A evolução das técnicas de rinoplastia está intimamente relacionada com o melhor conhecimento anatômico e funcional do nariz. A observação de que a incompetência das válvulas nasais pode ser responsável por até 50 por cento das queixas obstrutivas vem sendo confirmada através de diversos estudos. A utilização de enxertos expansores (spreader grafts) para ampliação das válvulas internas já foi bem estabelecida, no entanto, ainda não foi bem estudada de forma objetiva. Objetivo: A finalidade deste estudo foi avaliar prospectivamente a utilização de enxertos expansores na rinoplastia, fazendo-se uma análise objetiva do grau de melhora da patência nasal dos pacientes através da rinometria acústica e do espelho de Glatzel modificado, bem como uma análise subjetiva da qualidade de respiração dos mesmos pacientes mediante um escore preestabelecido. Metodologia: Foram estudados vinte pacientes submetidos à rinoplastia com utilização de enxertos expansores. Os pacientes foram avaliados no pré-operatório através de análise subjetiva através de questionário de qualidade respiratória - e objetiva, através de medidas da área de secção mínima transversa correspondente à válvula nasal interna mediante a rinometria acústica, e, através do espelho de Glatzel modificado. Após 90 a 120 dias da cirurgia, novas medidas foram realizadas, comparando-as com os resultados obtidos no pré-operatório. Os valores obtidos foram abordados sob a forma de variáveis quantitativas e analisados de acordo com a média e o desvio-padrão pelo teste não paramétrico de Wilcoxon. Conclusão: As medidas referentes às válvulas internas obtidas mediante rinometria acústica foram superiores quando comparados o momento pós-operatório com o pré-operatório dos lados direito e esquerdo. Quando analisados os valores obtidos através do espelho de Glatzel modificado, também observou-se que houve um acréscimo das médias se comparado o pós com o pré-operatório. A análise subjetiva da sensação de patência nasal demonstrou uma melhora na qualidade respiratória e apresentou significância estatística Background: The evolution of rhinoplasty techniques is closely related to the best knowledge of anatomy and function of the nose. The observation that the nasal valve incompetence may be responsible for up to 50 percent of obstructive symptoms has been confirmed by several studies. Using spreader grafts for internal valves expansion has been well established; however, it has not been well studied objectively. Objective: The purpose of this study was to prospectively evaluate the use of spreader grafts during rhinoplasty. We analyzed objectively the improvement degree in the nasal patency of patients through acoustic rhinometry and modified Glatzels mirror. We also analyzed the subjective improvement degree through a breathing quality score. Method: We studied twenty patients undergoing rhinoplasty with spreader grafts. Patients were evaluated preoperatively through subjective means-by a quality in breathing questionnaire-and objective analysis, by measuring the minimum cross sectional area (corresponding to the internal nasal valve) by acoustic rhinometry and through a modified Glatzels mirror. After 90 to 120 days, new measurements were made and then compared with those obtained preoperatively. The values were addressed in the form of quantitative variables and analyzed according to the mean and standard deviation by the nonparametric Wilcoxon test. Conclusion: The measures relating to the internal valves obtained by acoustic rhinometry were higher when the moment after surgery was compared with the preoperative moment on the left and the right sides. The results obtained by the modified Glatzels mirror also showed an increase in the measures in both sides. Analysis of subjective sensation of nasal patency demonstrated an improvement in quality of breathing with statistical significance

Introdução: O Erlotinibe é um inibidor oral da tirosina quinase localizada no domínio intracelular do receptor do fator de crescimento epidérmico (EGFR). É uma droga ativa contra o carcinoma epidermóide de cabeça e pescoço (CECCP) que apresenta alta expressão deste receptor, demonstrando desta forma possível sinergismo com a quimioterapia e a radioterapia. Objetivo: Avaliar a expressão do EGFR e da proteína Akt fosforilada por imuno-histoquímica como fator preditivo a resposta terapêutica ao Erlotinibe em um estudo fase II que incluiu 32 pacientes com CECCP localmente avançado; também foram analisados mutações do gene EGFR nos éxons 18,19,20 e 21. Pacientes e métodos: Neste estudo pacientes portadores de CECCP localmente avançado foram tratados com uma combinação de Cisplatina 100mg/m2 intravenoso, administrada nos dias 8, 29 e 50 do tratamento; e radioterapia na dose de 70 Gy administrada em 39 frações a partir do dia 8. O Erlotinibe foi iniciado uma semana antes da radioterapia e mantido até o último dia da radioterapia. Biópsias pré-tratamento, extraídas dos blocos de parafina, foram analisadas por imunohistoquímica para avaliar a expressão do EGFR e da Akt fosforilada. O resultado dessas amostras foi quantificado por um programa de análise digital de imagem. O status mutacional do gene EGFR (nos éxons 18, 19,20 e 21) foi analisado utilizando PCR convencional e sequenciamento. Resultados: A resposta completa ao tratamento ocorreu em vinte pacientes (62,5%), sendo que dois foram tratados com Laringectomia de resgate e ficaram sem evidência de doença. A análise de sobrevida com relação ao estadiamento e com o sítio anatômico evidenciou diferença estatisticamente significativa (p= 0.05). A análise das proteínas EGFR e p-Akt por imuno-histoquímica, quando os sítios estavam agrupados não apresentou valor preditivo de resposta ao tratamento; no entanto ao avaliarmos os sítios anatômicos separadamente, apenas a quantificação de EGFR em hipofaringe foi uma variável preditiva de resposta ao tratamento com erlotinibe (p=0.05). Em relação às análises moleculares nenhuma mutação foi detectada no seqüenciamento dos éxons estudados da proteína EGFR. Conclusão: A expressão do EGFR parece ser um fator preditivo à reposta terapêutica, no entanto outros estudos com identificação de outros biomarcadores e amostras maiores são necessários para elucidar quais pacientes com CECCP podem ser beneficiados com este tratamento Purpose: Erlotinib, an oral tyrosine-kinase inhibitor, is active against squamous cell carcinoma of the head and neck (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the expression of EGFR and phosphorylated AKT by immunohistochemistry as predictors of response to Erlotinib in a cohort of 32 locally advanced HNSCC, enrolled in a Phase II trial. In addition, we assessed mutation on hotspots of EGFR gene (exons18,19,20,21). Patients and Methods: This study was conducted in a Phase I/II trial of cisplatin 100 mg/m2 on days 8, 29 and 50; and radiotherapy 70 Gy starting on day 8. Erlotinib was started orally 1 week before chemo radiation and continued daily just to the last day of chemo radiation. Pretreatment archival tumor specimens were evaluated for EGFR and phosphorylated-Akt (p-Akt) by immunohistochemistry. These immunostains were quantified by digital image analysis. EGFR gene mutational status was also assessed using conventional PCR and sequencing. Results: Complete response to treatment occurred in twenty patients (62.5%), and two were treated with salvage laryngectomy and were without evidence of disease. Survival analysis in relation to the staging and the tumor site showed a statistically significant difference (p = 0.05). Analysis of EGFR protein and p-Akt by immunohistochemistry, when sites were grouped showed no predictive value for treatment response, however when evaluating the anatomical sites separately, only the quantification of EGFR in the hypopharynx was a significant predictor of response to treatment with erlotinib (p = 0.05). Regarding the molecular analysis no mutations were detected in the sequencing of the exons studied EGFR protein. Conclusion: The expression of EGFR seems to be a predictive factor for response to therapy, although other studies with identification of other biomarkers and larger samples are needed to elucidate which patients may benefit HNSCC with this treatment

INTRODUÇÃO: Pacientes com carcinomas das vias aerodigestivas superiores (VADS) apresentam um alto risco de desenvolver outros cânceres tanto simultaneamente quanto subsequentemente. A maioria destes tumores ocorre nas VADS, pulmões ou esôfago. A tríplice endoscopia (laringoscopia, endoscopia digestiva alta e broncoscopia) possibilita o diagnostico de lesões precursoras e de tumores invasivos. No entanto, a maioria dos estudos limita-se a descrever a frequência de diagnósticos, mas não os resultados do tratamento e o impacto na sobrevida. OBJETIVOS: Avaliar a importância da tríplice endoscopia para o diagnóstico de neoplasias primárias múltiplas e as diferenças no estadiamento e nas taxas de sobrevida de pacientes com carcinoma epidermóide de VADS. Caracterizar o perfil e analisar fatores de risco para neoplasias primárias múltiplas. MÉTODOS: Trata-se de estudo caso-controle retrospectivo em que foram incluídos pacientes com carcinoma epidermóide de VADS, submetidos à tríplice endoscopia antes do início do tratamento (grupo tríplice endoscopia), pareados, por sexo, idade e localização, estádio clínico e tratamento do tumor primário, com pacientes não submetidos à tríplice endoscopia na avaliação inicial (grupo controle). RESULTADOS: Foram incluídos 135 pacientes em cada grupo. No grupo tríplice endoscopia ocorreram mais diagnósticos de segundo tumor primário (STP), 34 (17 simultâneos e 17 metacrônicos), do que no grupo controle, 20 (1 simultâneo e 19 metacrônicos). Não foi identificada diferença significativa entre o estadiamento dos tumores de grupo tríplice endoscopia e do grupo controle. As curvas de sobrevida global, específica por câncer, livre de doença e pós-STP foram semelhantes nos dois grupos. A sobrevida livre de STP foi maior no grupo controle. Na análise multivariada foram identificados como fatores prognósticos independentes para a sobrevida, o sexo (feminino, RR 0,51, IC 0,30 0,88), a idade (maior que 57 anos, RR 1,73, IC 1,29 2,31), a localização do tumor primário (laringe, RR 0,60, IC 0,39 0,93), o estádio N (N2 e N3, RR 1,78, IC 1,26 2,51) e o estádio clínico do tumor primário (III e IV, RR 2,75, IC 1,69 4,46). As variáveis independentes relacionadas ao diagnóstico e à ocorrência de STP foram a realização de tríplice endoscopia (RR 1,93; IC 95% 1,02 - 3,65), o tipo de tratamento do tumor primário (cirurgia exclusiva, RR 3,14; IC 95% 1,11 - 8,85) e o tempo de seguimento (maior que 24 meses, RR 3,69; IC 95% 1,19 - 11,47). CONCLUSÃO: Não ocorreu diferença no estádio clínico dos STP e nas sobrevidas global, específica por câncer, livre de doença e pós-STP entre o grupo tríplice endoscopia e o grupo controle. Foram identificados como fatores independentes relacionados ao diagnóstico e a ocorrência de STP o tratamento realizado (cirurgia exclusiva), o tempo de seguimento (maior que 24 meses) e a realização da tríplice endoscopia. INTRODUCTION: Patients with upper aerodigestive tract (UADT) carcinomas have a high risk of developing others cancers simultaneously or subsequently. Most of these tumors occur in UADT, lungs or esophagus. Triple endoscopy (laryngoscopy, endoscopy and bronchoscopy) enables the diagnosis of premalignant and invasive tumors. However, most of the studies describe only the frequency of the diagnosis, but not the results of treatment and its impact on survival. OBJECTIVES: To evaluate the importance of triple endoscopy for the diagnosis of multiple primary tumors and the differences in clinical stage and survival rates of patients with squamous cell carcinoma of the UADT. To characterize and to analyze the risk factors for multiple primary tumors. METHODS: This is a case-control study that included patients with squamous cell carcinoma of the UADT, that were submitted to a triple endoscopy before the first treatment (triple endoscopy group), matched by sex, age and location, clinical stage and treatment of primary tumor, with patients not undergoing triple endoscopy in the initial evaluation (control group). RESULTS: One hundred and thirty five patients were included in each group. The diagnosis of second primary tumor (SPT) was more frequent in the triple endoscopy group than in the control group, 34 (17 simultaneous and 17 metachronous) and 20 cases (1 simultaneous and 19 metachronous), respectively. No significant difference was found between the clinical stage of triple endoscopy group and the control group. The curves of overall survival, cancer specific, disease-free and after SPT were similar in both groups. The SPT free survival was higher in the control group. In the multivariate analysis were identified as independent prognostic factors for survival, sex (women, RR 0.51, CI 0.30 - 0.88), age (older than 57 years, RR 1.73, CI 1.29 - 2.31), the primary tumor site (larynx, RR 0.60, CI 0.39 - 0.93), N stage (N2 and N3, RR 1.78, CI 1.26 - 2.51) and the clinical stage of primary tumor (III and IV, RR 2.75, CI 1.69 - 4.46). The independent variables related to the diagnosis and the occurrence of SPT were triple endoscopy (RR 1.93, 95% CI 1.02 - 3.65), the primary tumor treatment (surgery alone, RR 3.14, 95% CI 1.11 - 8.85) and follow-up (greater than 24 months, RR 3.69, 95% CI 1.19 - 11.47). CONCLUSION: There was no difference in the clinical stage of the SPT and overall survival, cancer specific, disease-free and post SPT between the triple endoscopy group and control group. As independent predictors for the diagnosis and the occurrence of SPT were treatment performed (just surgery), follow-up time (greater than 24 months) and triple endoscopy.

Introdução: A ciclina D1 constitui um importante regulador do ciclo celular e pode funcionar como co-regulador de transcrição. A superexpressão da ciclina D1 tem sido associada ao desenvolvimento e progressão do câncer. A degradação irregular da ciclina D1 pode ser responsável pelos seus níveis elevados em algumas neoplasias malignas. A ciclina D1, além disso, modula indiretamente a estrutura da cromatina e transcrição de genes envolvidos na proliferação e diferenciação. Mutações, amplificação e superexpressão da ciclina D1, que alteram a progressão do ciclo celular, são observadas frequentemente em várias apresentações de neoplasias malignas, incluindo o carcinoma epidermóide de laringe, e as elucidações inferidas destas observações podem trazer melhor entendimento à oncogênese. Objetivo: O objetivo deste estudo foi comparar a expressão imunoistoquímica de ciclina D1 e a ocorrência de metástase linfática em estádios III e IV de carcinoma epidermóide de laringe. Métodos: Estudo retrospectivo, coorte longitudinal, por avaliação imunoistoquímica e quantificação digital da imunoexpressão nuclear e citoplasmática de ciclina D1 em espécimes de tumor preservados em parafina oriundos de pacientes consecutivos submetidos à cirurgia oncológica radical, entre 1999 e 2004. A sobrevida global dos pacientes foi avaliada, bem como a idade, sexo, tabagismo, estado de comprometimento linfático, grau de diferenciação e estadiamento (pTNM). A análise estatística teve como significância valores de p< 0.05. A curva de sobrevida foi elaborada utilizando o método de Kaplan-Meier. Resultados: Houve imunomarcação citoplasmática em 566 (1,2%) células, imunomarcação nuclear em 13788 (29,6%) células, a relação do IPc e IPn foi de 0,007 (0,7%), ausência de imunomarcação celular foi observada em 32210 (69,1%) células, perfazendo um total de 46554 (100%) células investigadas. Entre os 28 (59,5%) casos que não apresentaram metástase linfática, o IPn foi de 26,8 (9,7 - 46,9) e o IPc foi de 0,1 (0 0,3); naqueles 19 (40,4%) em que foi observada metástase linfática, o IPn foi de 26,7 (16,7 39,0) e o IPc foi de 0,3 (0 - 1,0). Conclusões: Não houve associação estatisticamente significante entre expressão nuclear e citoplasmática de ciclina D1, em carcinoma epidermóide primário de laringe, e ocorrência de metástase linfática cervical, graus de diferenciação histológica, bem como recidiva loco-regional e metástase hematogênica. O presente estudo não subsidia a superexpressão de ciclina D1 como fator limitante de sobrevida global Background: Cyclin D1 is an important regulator of cell cycle progression and can function as a transcriptional co-regulator. The overexpression of cyclin D1 has been linked to the development and progression of cancer. Abnormal cyclin D1 degradation appears to be responsible for the increased levels of cyclin D1 in several cancers. Recent findings have identified novel mechanisms involved in the regulation of cyclin D1 stability. Cyclin D1 belongs to the family of cyclin proteins which function as the regulatory subunits of cyclin/cyclin dependent kinase (Cdk) holoenzymes that regulate entry into and progression through the cell cycle. Cyclin D1 expression is induced upon stimulation by growth factors (e.g. EGF, IGF-I/II), aminoacids, hormones, and oncogenes such as Ras, Src, ErbB2, and SV40 T antigen. Cdk4 and Cdk6 can partner with cyclin D1 in early to mid-G1 phase to phosphorylate and inactivate the cell cycle inhibitory function of the retinoblastoma protein (pRB) in cooperation with cyclin E/Cdk2. Cyclin D1 is also known to modulate local chromatin structure and transcription of genes involved in proliferation and differentiation through CDK-independent association with histone acetylases (e.g. CBP, P/CAF) and deacetylases. Mutations, amplification or overexpression of cyclin D1, which alters cell cycle progression, are observed frequently in a variety of tumors, including laryngeal squamous cell carcinoma, and may contribute to oncogenesis. Methods: This was a retrospective study by immunohistochemical determination of cyclin D1 in fixated and paraffin-embedded tumour especimens from 47 consecutive patients with squamous cell carcinoma in larynx treated by curative oncological surgery from 1999 to 2004. Survival of patients was related to age, gender, nodal status and stage at termination of treatment. Significant differences were considered for p

O objetivo deste estudo foi verificar a hipótese que condições orais (uso de prótese dentária removível, machucados recorrentes devidos a prótese mal adaptada ou a dentes mal posicionados ou quebrados, consumo freqüente de bebidas quentes e escovação dentaria irregular ou pouco freqüente) poderiam interagir com tabaco, álcool, padrão alimentar e condição socioeconômica na carcinogênese oral. Foi realizado estudo de caso-controle de base hospitalar (Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo), com 124 pacientes (22 mulheres e 102 homens) com câncer de boca e igual número de controles sem experiência de câncer atendidos no mesmo hospital para condições não relacionadas à boca. Os pacientes do grupo caso apresentavam neoplasia em diferentes sítios da boca: mucosa jugal (5), área retromolar (6), lábio inferior, aspecto interno (10), gengiva (11), palato (17), assoalho bucal (27) e língua (48). A seleção dos pacientes do grupo controle observou pareamento individual por sexo e idade (± cinco anos) com o grupo caso; e pareamento por freqüência quanto à condição de fumantes ou ex-fumantes (não-fumantes não foram incluídos no estudo). Todos os participantes do estudo responderam um questionário detalhando características sócio-demográficas, padrão de consumo de bebidas alcoólicas e tabaco, hábitos alimentares e informações sobre as condições orais de interesse do estudo. A análise estatística usou modelos multivariados de regressão logística condicional, com estrutura hierárquica dos níveis de determinação. Como resultado desse procedimento de análise, indicou-se que o uso de prótese dentária não associou com câncer de boca (p=0,090); no entanto, a lembrança de feridas recorrentes na mucosa oral devido ao uso de prótese mal adaptada teve associação positiva com a chance da doença (p=0,007). A lembrança de machucados por dentes quebrados ou fora de oclusão não associou com câncer de boca em fumantes (p=0,084). A associação entre câncer de boca e consumo de bebidas quentes ficou no limiar da significância estatística (p=0,050). Machucados recorrentes na mucosa oral, devido a próteses mal adaptadas pode ser um fator que contribui com a carcinogênese dos tumores da boca em fumantes; e esse resultado não seria devido à falta de controle pelos demais fatores relevantes na determinação do câncer bucal. The aim of this study was to assess the hypothesis that conditions of mouth status (the use of dentures, recurrent sores by ill-fitting dentures or ill-positioned or broken teeth, frequent intake of hot beverages and irregular or infrequent tooth brushing) may interact with tobacco, alcohol, diet and socioeconomic status in the carcinogenesis of oral cancer. We performed a hospital-based (\"Hospital das Clínicas\", School of Medicine, University of São Paulo) case-control study comprising 124 patients (22 women and 102 men) with oral cancer, and the same number of controls without previous or current experience of cancer and with treatment needs unrelated to mouth status. Patients in the case group presented tumors at different sites of the mouth: cheek mucosa (5), retromolar area (6), lower lip, inner aspect (10), gum (11), palate (17), floor of mouth (27) and tongue (48). The selection of controls observed the concurrent pairing for gender and age (± five years) with cases, and matching by frequency by smoking status: current or former smokers (never-smokers were not included in the study). All participants responded a detailed questionnaire on socio-demographic characteristics, patterns of alcohol and tobacco consumption, dietary habits and information on conditions of mouth status. Data analysis used multivariate models of conditional logistic regression, observing a hierarchical structure of levels of determination. As a result of this analytical scheme, the use of dentures was reported as not associated with the adjusted odds of mouth cancer (p=0.090). When adjusted by covariates on smoking, alcohol drinking and diet, the association of recurrent sores caused by ill-fitting dentures with the odds of mouth cancer was significant (p=0.007). However, recurrent sores by defective teeth were not indicated as a significant contributing factor for the odds of oral cancer in smokers. The association between mouth cancer and the frequent intake of hot beverage was assessed at the threshold of significance (p=0.050). Recurrent oral sores due to ill-fitting dentures may be a contributing factor for the carcinogenesis of mouth neoplasms in smokers; and this result is unlikely to be due to insufficient control of covariates.

Introdução: O carcinoma epidermóide de cabeça e pescoço avançado é uma doença de difícil tratamento. Apesar dos avanços nas técnicas de diagnóstico e tratamento nos últimos 30 anos não ocorreram ganhos significativos em sobrevida. A falha no tratamento ocorre principalmente pela recidiva locorregional e freqüentemente impede a realização de tratamentos de resgate. Com o desenvolvimento da imunoterapia novas abordagens tem sido descritas para o combate ao câncer. Estudos em animais demonstraram a redução de tumores com a utilização de vacinas de DNA contendo a HSP-65 do Mycobacterium leprae. Neste estudo avaliou-se a utilização desta proteína em pacientes portadores de carcinoma epidermóide de cabeça e pescoço em estádio avançado e fora de possibilidades terapêutica curativa pelos métodos convencionais. Objetivos: Testar a viabilidade de realização da injeção intratumoral do DNA HSP65 nesse grupo de doentes, avaliar a resposta tumoral através da análise comparativa do volume, pesquisar a transfecção do DNA HSP65 do M. Leprae e verificar se o tratamento realizado apresentou impacto na evolução dos pacientes. Casuística e métodos: Foram incluídos 21 pacientes em três grupos. Cada grupo recebeu diferentes doses da vacina de DNA HSP-65 do Mycobacterium leprae: 150, 600 e 400µg, através de aplicações intratumorais guiadas por ultra-som com Doppler. Foram realizadas tomografias computadorizadas antes e após o tratamento, para avaliação da resposta tumoral através da comparação de volume tumoral. Realizaram-se biópsias antes e após o tratamento, e o material foi submetido a reação em cadeia da polimerase (Rt-PCR) para identificar a transfecção do DNA injetado. Durante o protocolo os pacientes foram acompanhados para observação de eventos adversos que pudessem ser relacionados à medicação. Resultados: Dos 21 pacientes, sete faleceram antes do término do protocolo. Nos 13 pacientes passíveis de análise, ocorreram quatro respostas parciais e estabilidade da lesão em um caso. Em nove casos houve progressão da doença. Dois pacientes encontram-se vivos em seguimento a mais de oitocentos dias do inicio do protocolo. Os eventos adversos ocorridos foram principalmente aumento da dor local e edema. Não foi possível comprovar a transcrição do DNA injetado no Rt-PCR pela ocorrência de um resultado falso positivo. Conclusões: A aplicação foi segura na dose de 400µg por aplicação. Não foi possível comprovar a transfecção de DNA de HSP65. Nos pacientes que apresentaram diminuição do volume tumoral parece ter havido benefício clínico. Introduction: The squamous cell carcinoma of the head and advanced neck is an disease difficult to treat. Despite the advances in diagnosis and treatment in last the 30 years had not occurred major survival improvements. The treatment failure occurs mainly locorregionaly and recurrences frequently canot be rescued. immunotherapy has had encouraging results in the last years. Studies in animals had demonstrated the reduction of tumors with the DNA vaccine containing HSP-65 of the Mycobacterium leprae. In this study we evaluate the use of this protein in patients with avdanced head and neck carcinoma, stages II and IV without possibilities of curative treatment. Objectives: To test the viability of accomplishment of the intratumoral injection of DNA HSP65 in this group of patients, test its effectiveness through the comparative analysis of the volume, to verify transfeccion of the DNA injected and to see if the carried through treatment presented impact in the evolution of the patients. Patients and methods: 21 patients in 3 groups of doses 150,600 and 400µg of the vaccine of DNA HSP-65 of M leprae, through intratumoral applications guided by USG Doppler repeated 3 times every 21 days. CT scans before and after the treatment had been carried through, for evaluation of the tumoral response through the comparison of tumoral volume. We also did biopsis before and after the treatment, and the material was submitted the Rt-PCR in search of tranfeccion of the injected DNA. During the protocol the patients had been evalueted to rule observe adverse events that could be related to the medication. Results: Of 21 patients, seven died before the end of the protocol. In the 13 suitable for analysis, 4 partial responses and stability of the disese in 1 case had occurred. In 9 cases the tumors progressed. Two patients are still alive, with more than eight hundred days of the beginning of the protocol. The adverse events occurred mainly as an increase of local pain and edema. It was not possible to prove the transcription of the DNA injected in the Rt-PCR because of the occurrence of positive a false result. Conclusions: The application was secure in the dose of 400mcg . We saw reduction of tumoral volume in 5 of the 13 patients suitable for analysis, four partial responses and one stable disease. In the patients who had presented reduction of the tumoral volume there seems to be clinical benefit. It was not possible to prove the transfeccion of the injected DNA.

O carcinoma epidermoide da região da cabeça e pescoço (CECP) é uma doença de alta prevalência, no Brasil e no mundo, e com grande impacto na qualidade de vida dos pacientes. Mais frequentemente, ocorre em pacientes ao redor da sexta década de vida, com longo histórico de tabagismo e etilismo. Nota-se, porém, um importante aumento na sua incidência em uma população mais jovem, em geral sem histórico de exposição duradoura aos fatores de risco clássicos, o que nos faz questionar se não se trata de uma doença de características distintas. Os objetivos deste estudo foram avaliar aspectos demográficos, clínicos e anatomopatológicos de pacientes com CECP em uma faixa etária inferior a 40 anos, comparando-os com pacientes de maior idade, especialmente em relação à sobrevida, exposição a fatores de risco, expressão de marcadores biológicos em amostras tumorais e não tumorais (margens livres de doença), bem como a presença do Papilomavirus Humano (HPV). Realizou-se estudo transversal de pacientes com carcinomas de cavidade oral (exceto lábio), orofaringe, laringe e hipofaringe, prospectivamente incluídos em um banco de tumores de CECP no período de 2002 a 2010 pelo grupo de pesquisa GENCAPO. Foram coletados dados demográficos, clínicos e patológicos para ambos os grupos de doentes, e realizou-se uma análise por pareamento em relação aos marcadores imunoistoquímicos p53, Ki-67, EGFR, VEGF e p16, em amostras tumorais e de mucosas normais. As análises de sobrevida global e livre de doença, bem como as comparações entre o tabagismo e o etilismo foram feitas com a população total da amostra. A incidência de tabagismo foi menor nos pacientes =40 anos. O tabagismo e o etilismo foram menos intensos entre os pacientes

Os genes homeobox são responsáveis por codificar proteínas nucleares que agem como fatores de transcrição durante o desenvolvimento embrionário, regulando proliferação e diferenciação celular. A expressão alterada do gene homeobox PROX1 já foi identificado em diferentes neoplasias, incluindo mama, esôfago, fígado, sistema biliar, linfomas e cavidade bucal. Este trabalho teve como objetivo avaliar os efeitos da superexpressão do gene PROX1 em linhagem celular derivada de carcinoma epidermóide bucal nos mecanismos de proliferação e diferenciação celular, apoptose e perfil global de expressão gênica. Após a superexpressão deste gene na linhagem celular SCC-9, foi realizada a análise de proliferação por meio dos ensaios de curva de proliferação celular, citometria de fluxo, índice de incorporação de BrdU ao DNA e expressão de Ki67. A diferenciação celular foi verificada por meio de reações imunocitoquímicas para as citoqueratinas 1, 10, 13, 14, 16, 18 e 19 e a apoptose foi avaliada por meio de células positivas para anexina-V e iodeto de propídeo. O ensaio de microarray foi realizado para avaliação do perfil global de expressão gênica na linhagem celular SCC9 com superexpressão do gene PROX1. Observou-se que a superexpressão do gene PROX1 promove redução da proliferação celular, bem como reduz a expressão das citoqueratinas 1, 13, 18 e 19. Não houve alteração na taxa de apoptose entre as células com superexpressão do gene PROX1 e controles. Os resultados do microarray revelaram a expressão diferencial significante de genes envolvidos com os processos de desenvolvimento, adesão e invasão celular. Desta maneira, estes resultados são fortemente sugestivos de que o gene PROX1 inibe a proliferação celular e contribui para a diferenciação do carcinoma epidermóide bucal. Homeobox genes encode transcription factors with an important role during normal development by controlling cellular proliferation and differentiation. Altered expression of PROX1 homeobox gene is related to many cancers, including those of the breast, esophagus, liver, billiary system and lymphomas. The aim of this study was evaluate the effects of PROX1 overexpression, in an oral squamous cell carcinoma cell line, on cellular proliferation and differentiation, apoptosis as well as gene expression prolfile. After overexpression of PROX1 gene in SCC9 cell line, proliferation was assessed by proliferation curve, flow citometry, BrdU incorporation to DNA and Ki67 expression. Cell differentiation was verified by immunocytochemistry to cytokeratins 1, 10, 13, 14, 16, 18 and 19 and apoptosis was measured by annexin V positive cells. Gene expression profile was analyzed by microarray in PROX1-overexpressing cells and control. PROX1-overexpressing cells showed a statistically significant decrease in proliferation as well cytokeratin 1, 13, 18 and 19 expression. No significant differences from controls and PROX1- overexpressing cells were observed in apoptosis. Microarray analyses showed differential expression of genes related to development, cellular adhesion an invasion. Our results strongly suggest that overexpression of PROX1 inhibit cell proliferation and contributes to differentiation of oral squamous cell carcinoma.

Muitos pacientes submetidos à tireoidectomia por Carcinoma Papilífero da Tireoide (CPT) têm doença linfonodal subclínica no momento da cirurgia. A mutação BRAF T17799A (V600E) é um evento comum no CPT e alguns estudos demonstram correlação entre a mutação e características de maior agressividade tumoral, incluindo a presença de metástases linfonodais. O esvaziamento eletivo do compartimento central ganha aceitação, uma vez que alguns estudos evidenciam que a presença de metástases linfonodais aumenta o risco de recidiva e mortalidade. Devido ao grande potencial de complicações do esvaziamento do compartimento central, o objetivo deste trabalho foi avaliar a associação entre a presença da mutação BRAF T17799A (V600E), a presença de metástases linfonodais e fatores clínicos e histopatológicos de pior prognóstico. Métodos: 51 casos consecutivos de pacientes com CPT foram submetidos à tireoidectomia total e ao esvaziamento eletivo ou terapêutico do compartimento central. Em todos os pacientes foi pesquisada a mutação BRAF T17799A (V600E) no tecido tireoidiano com Carcinoma Papilífero de Tireoide. Resultados: Cinquenta e quatro por cento (54,9%) dos pacientes apresentaram metástases linfonodais. Seis pacientes apresentaram metástases laterais confirmadas por punção aspirativa por agulha fina no pré-operatório e 22 pacientes (43%) apresentaram metástases não detectadas no pré ou no intra operatório A mutação BRAF T17799A (V600E) foi encontrada em 15 pacientes portadores de CPT (29,4%). A presença da mutação não teve associação estatisticamente significante para sexo, idade, tamanho do tumor, extensão extratireoidiana, multicentricidade, embolização angiolinfática e metástases linfonodais. As metástases linfonodais se associaram à multifocalidade (p = 0,005) e invasão angiolinfática (p = 0,003) na análise univariada. Conclusão: A presença da mutação BRAF T17799A (V600E) não se associou à metástases linfonodais em nosso estudo. A multifocalidade e a detecção de invasão angiolinfática no CPT foram os fatores mais importantes na predição de metástases linfonodais Background: Many patients undergoing thyroidectomy for Papillary Thyroid Carcinoma (PTC) have subclinical node disease at the time of surgery. The BRAF T17799A (V600E) mutation is a common event in PTC and some studies have demonstrated a correlation between the mutation and aggressive characteristics including lymph node metastasis. Prophylactic Central Node Dissection (CND) is gaining acceptance in the treatment of PTC as studies have shown nodal disease increases local recurrence and may alter mortality. Given the potential complications of CND, the aim of this study was to determine the correlation among BRAF mutation, lymph node metastasis and clinical and histopathological factors of worse prognosis. Methods: A total of 51 consecutive cases of patients with PTC underwent total thyroidectomy and routine prophylactic (CND) or therapeutic neck dissection when metastases were found. All patients were tested for the BRAF mutation. Results: Overall, positive lymph nodes were found in Fifty four per cent9% of patients. Six patients had lateral metastases confirmed by fine needle aspirative cytology and 22 patients (43%) had occult metastases. The BRAF mutation was found in 15 patients (29.4%). BRAF was not correlated with sex, age, size of tumor, multifocality, extrathyroid extension or lymph node metastases. Lymph node metastases were correlated with multifocality (p = 0.005) and angiolymphatic invasion (p = 0.003) in univariate. Conclusions: The BRAF mutation was not correlated with lymph node metastases in our study. Multifocality and angiolymphatic invasion were important factors for predicting lymph node metastases

O carcinoma epidermóide de cabeça e pescoço (CECP) é um problema de saúde relevante no mundo, por sua prevalência e agressividade. Os papéis do tabaco e do álcool estão bem definidos na sua etiologia, mas uma minoria crescente dos pacientes acometidos pela doença não é tabagista ou etilista. A infecção pelo papilomavirus humano (HPV) parece ser responsável por parte desses casos. Sugere-se que o CECP que acomete pacientes não tabagistas e não etilistas (NTNE) tenha processos carcinogênicos e evolução clínica distintos daqueles de pacientes tabagistas e etilistas (TE). Os objetivos desse estudo foram verificar se os aspectos demográficos, clínicos e histopatológicos de pacientes com CECP são diferentes conforme os hábitos tabágico e etílico; verificar se os CECPs de pacientes NTNE e TE diferem em relação à positividade para HPV; e comparar a sobrevida específica pela doença e a expressão de marcadores biológicos em amostras tumorais e de mucosa normal do trato aerodigestório de pacientes NTNE e de pacientes TE. Para tanto, realizamos estudo transversal de pacientes com carcinomas epidermóides de cavidade oral (exceto lábio), orofaringe, laringe e hipofaringe, prospectivamente incluídos em um banco de tumores de CECP de 2001 a 2009, pelo grupo de pesquisa multi-institucional GENCAPO. Seus dados demográficos, clínicos e patológicos foram analisados conforme os hábitos de tabagismo e etilismo. Através de análise de pareamento, pacientes NTNE e TE foram comparados em relação à sobrevida, à positividade para o HPV no tumor por reação em cadeia da polimerase (PCR) e aos marcadores imunohistoquímicos p53, FHIT, Ki-67, VEGF, EGFR e p16 tanto em amostras tumorais como de epitélio não tumoral. Dos 1633 pacientes selecionados, 80 eram NTNE (4,9%), 1374 TE (84,1%), 140 tabagistas atuais ou no passado mas não etilistas (TNE:8,6%) e 39 apenas etilistas atuais ou no passado, mas não tabagistas (NTE:2,4%). O grupo de pacientes NTNE constituiu-se principalmente por mulheres, preferencialmente idosas, com tumores da cavidade oral, diferentemente de pacientes tabagistas e/ou etilistas (p

INTRODUÇÃO: a imunidade celular de pacientes com carcinoma epidermóide de cabeça e pescoço tem sido foco de muitos estudos nas últimas décadas. As alterações do sistema imune parecem estar relacionadas com a progressão da doença. A avaliação da imunidade celular desses casos é necessária para programar estratégias de imunoterapia. A deficiência nutricional, o tamanho tumoral e a recidiva são fatores que também podem estar relacionados com a piora imunitária e clínica. O objetivo deste trabalho foi verificar se portadores de carcinoma epidermóide de cabeça e pescoço têm imunidade celular e estado nutricional diferente de controles e sua correlação com tamanho tumoral e recidiva. MÉTODOS: foram avaliados 155 pacientes admitidos nos serviços de cirurgia de cabeça e pescoço e cirurgia geral do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, entre 16 de agosto de 2005 a 31 de julho de 2006. Houve 52 controles e 103 casos com diagnóstico de carcinoma epidermóide de trato aerodigestivo alto, subdivididos em 29 casos pré-tratamento, 47 pós-tratamento sem doença e 27 pós-tratamento com doença. Foi realizada entrevista clínica, contendo dados demográficos, presença de tabagismo, etilismo e co-morbidades, e avaliado o índice de Karnofsky. Dados do tumor e tratamento foram anotados. Foi realizada avaliação nutricional antropométrica, através da medida do peso, estatura e índice de massa corpórea (IMC). A avaliação da composição corpórea foi feita através de bioimpedância elétrica, utilizando-se a porcentagem de massa magra em homens e mulheres. Os critérios bioquímicos usados foram concentração plasmática de albumina e contagem total de linfócitos (CTL). A avaliação da imunidade celular foi feita através de testes cutâneos com 3 antígenos (PPD, tricofitina e candidina). O tamanho tumoral também foi medido. A análise estatística foi feita através de média, desvio padrão, ANOVA e Bonferroni para variáveis numéricas e teste qui-quadrado de Pearson para as categóricas. RESULTADOS: As médias de IMC, albumina e CTL foram diferentes entre os grupos (p

Os genes homeobox são uma família de genes reguladores que são vitais para vários aspectos do crescimento e diferenciação celular. Recentemente, implicações dos genes HOXA7, HOXC6 e TGIF na gênese e progressão tumoral vêm sendo verificadas. Entretanto, o envolvimento desses genes em carcinomas epidermóides (CE) de boca ainda não foi demonstrado. A possível presença de transcritos dos genes HOXA7, HOXC6 e TGIF em carcinomas epidermóides de boca e em tecidos não tumorais adjacentes (TN) foi analisada. Os transcritos dos genes foram amplificados por RT-PCR e sua localização celular determinada por hibridização in situ (ISH) com sondas de mRNA específicas. A amplificação do HOXA7 foi observada em 70% dos casos sendo 15% apenas nas amostras TN, 45% somente nos CEs e 10% em ambos tecidos. Nenhuma amplificação do HOXC6 foi observada. O TGIF foi amplificado em 80% dos casos, sendo 5% somente nas amostras TN, 20% nos CEs e 55% em ambos tecidos. Análises estatísticas mostraram que não havia diferença significante entre a amplificação do transcrito HOXA7 ou TGIF e o tipo de tecido analisado. Além disso, nenhuma associação entre a amplificação dos transcritos nas amostras CE e os aspectos clínicos foi observada. O sinal de hibridização in situ foi similar para os transcritos HOXA7 e TGIF. Nas amostras TN o sinal da ISH foi intenso no epitélio, ora disperso sendo mais proeminente na camada espinhosa ora mais proeminente nas camadas basais e suprabasais. Nos CEs os transcritos foram localizados por toda neoplasia sendo que o sinal era menor em áreas menos diferenciadas. Esses resultados mostram que o HOXC6 não está envolvido com a carcinogênese oral enquanto que a presença dos transcritos HOXA7 e TGIF principalmente em regiões bem diferenciadas dos carcinomas epidermóides de boca sugere uma participação desses genes nesta neoplasia Homeobox genes comprise a family of developmental regulators that are vital for several aspects of growth and differentiation. Recently HOXA7, HOXC6 and TGIF genes have been implicated with carcinogenesis and tumoral progression. However their involvement with oral squamous cell carcinomas (OSCC) has not been demonstrated yet. The possible presence of HOXA7, HOXC6 and TGIF transcripts in OSCC and adjacent non-tumoral tissues (NT) was verified. Transcripts were amplified by RT -PCR and its cellular localization was determined by in situ hybridization with specific riboprobes. Amplification of HOXA7 was seen in 70% of cases, 15% only in NT tissues, 45% only in OSCC samples and 10% in both tissues. No amplification of HOXC6 was observed. TGIF was amplified in 80% of cases, 5% only in NT tissues, 20% only in OSCC samples and 55% in both tissues. Statistical analysis showed that there was no significant difference between amplification of HOXA7 or TGIF and the type of tissue analyzed. Moreover, no association between amplification of transcripts in OSSC and clinical aspects was observed. ISH signal was similar for HOXA7 and TGIF transcripts. In NT tissues there was an intense expression in the epithelium, either in basal and suprabasal layers or disperse and more intense in the spinous layer. In OSCC transcripts were locali zed in all tumoral cells, but in poorly differentiated areas the signal was less intense. These results show that HOXC6 was not involved in oral carcinogenesis while the presence of HOXA7 and TGIF transcripts in OSSC, mostly in well differentiated regions, suggests a participation of these genes in OSCC