Objective: To complete a cost-minimization analysis (CMA) of the cost of sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) in the management of early-stage breast cancer (ESBC) in a hypothetical Ontario hospital setting. Methods: Decision-analysis modeling, with a decision-tree and Markov states, was used to estimate hospital costs for the two treatment options. The model was populated with data from the literature and costs from the Ontario Case Costing Initiative, a publicly accessible, government-sponsored, costing database. Model variability and parameter uncertainty were quantified by probabilistic sensitivity analysis (PSA). Results: The SLNB treatment algorithm was cost-minimizing compared to the ALND-only treatment option. The costs of treating postoperative complications did not contribute to the incremental average cost. Conclusion: A treatment algorithm that involves SLNB as the initial axillary-staging procedure in the setting of ESBC offers a cost-savings over the ALND-only option. This result is generalizable to all Ontario hospitals.

Objective: To complete a cost-minimization analysis (CMA) of the cost of sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) in the management of early-stage breast cancer (ESBC) in a hypothetical Ontario hospital setting. Methods: Decision-analysis modeling, with a decision-tree and Markov states, was used to estimate hospital costs for the two treatment options. The model was populated with data from the literature and costs from the Ontario Case Costing Initiative, a publicly accessible, government-sponsored, costing database. Model variability and parameter uncertainty were quantified by probabilistic sensitivity analysis (PSA). Results: The SLNB treatment algorithm was cost-minimizing compared to the ALND-only treatment option. The costs of treating postoperative complications did not contribute to the incremental average cost. Conclusion: A treatment algorithm that involves SLNB as the initial axillary-staging procedure in the setting of ESBC offers a cost-savings over the ALND-only option. This result is generalizable to all Ontario hospitals.

Prostate cancer (PCa) is the most common non-skin malignancy of men in developed countries. In spite of treatment with curative intent up to 30-40% of patients have disease recurrence after treatment, resulting from any combination of lymphatic, hematogenous, or contiguous local spread. The concept of early detection of PCa offer benefits in terms of reduced mortality, but at the cost of over-diagnosis and overtreatment of indolent disease. This is largely due to the random nature of conventional biopsies, with a risk of missing significant cancer and randomly hitting indolent disease. In the present thesis, diagnostic performance of MRI DWI and 11C Acetate PET/CT lymph node staging of intermediate and high risk PCa, was investigated, and additionally, predictive factors of regional lymph node metastases were evaluated. Further, additional value of targeted biopsies to conventional biopsies, for detection of clinically significant PCa, was investigated. In paper one and two, 53 and 40 patients with predominantly high risk PCa underwent 11C Acetate PET/CT and 3T MRI DWI, respectively, for lymph node staging, before extended pelvic lymph node dissection (ePLND). The sensitivity and specificity for PET/CT was 38% and 96% respectively. The sensitivity and specificity for MRI DWI was 55% and 90% respectively. In paper three, 53 patients with newly diagnosed PCa were included. All patients underwent multi-parametric MRI, followed by two cognitive targeted biopsies. Five more clinically significant cancers were detected by adding targeted biopsies to conventional biopsies. In paper four the value of quantitative and qualitative MRI DWI and 11C Acetate PET/CT parameters, alone and in combination, in predicting regional lymph node metastases were examined. ADCmean in lymph nodes and T-stage on MRI were independent predictors of lymph node metastases in multiple logistic regression analysis. In conclusion the specificity of diffusion weighted MRI and 11C Acetate PET/CT for lymph node staging was high, although the sensitivity was low. Predictive factors of regional lymph node metastases could be retrieved from diffusion weighted MRI and 11C Acetate PET/CT. By combining targeted biopsies with conventional biopsies the detection rate of clinically significant PCa could be increased.

Skin sensitization resulting for allergic contact dermatitis (ACD) is an occupational and environmental health issue. The allergic hazard for workers and consumers is a serious problem for individuals, employers and marketing certain products. Consequently, it is necessary to accurately identify chemicals skin sensitization potential. According to the new EU chemical regulation REACH (Registration, Evaluation, Authorization and Restriction of Chemicals), information of skin sensitization of chemicals manufactured or imported at or above 1 ton/year should be available. Currently, valid approaches assessing skin sensitization rely on animal testing, such as local lymph node assay (LLNA). However, it now ultimately eliminates using animals for this purpose. Based on the fact that a key step in the skin sensitization process is formatting a covalent adduct between allergic sensitizers and proteins and/or peptides in skin, a lot of additional approaches are proposed and developed for replacing or reducing animal used. In this research, three bioassays, 24 h growth inhibition toward Tetrahymena pyriformis, long term (24 h) and short term (30 min) bacterial toxicity (to Vibrio fischeri), and a kinetic glutathione chemoassay are applied for predicting the organic chemicals’ skin sensitization potential. The major results and conclusions obtained are listed as follows: 1. Toxicity enhancement (Te) of 55 chemicals comprising different sensitization potencies were determined and compared with their narcotic toxicity to predict their skin sensitization. Three linear regressions yielded for all allergic sensitizer without nonsensitizers for each bioassay. The linear regressions are improved after classifying sensitizers into five different reaction mechanistic domains. Correspondingly, five different slopes from various reaction mechanisms indicate a decreased sensitivity of toxicity enhancement to skin sensitization potential with order SNAr > SN2 > acylation ≈ Schiff base > aromatic Michael addition. Based on the fact that a key step in the skin sensitization process is forming a covalent adduct between allergic sensitizers and proteins and/or peptides, Te > 10 as a threshold is applied to discriminate these allergic sensitizers, with 100% accuracy for strong (with extreme) and weaker sensitizers, up to 72% accuracy for moderate sensitizers and less than 69% accuracy for nonsensitizers. Compared with these bioassays, a decreasing order of sensitivities is 24 h growth inhibition (Tetrahymena pyriformis) > 24 h growth inhibition (Vibrio fischeri) > 30 min bioluminescence inhibition (Vibrio fischeri). These three bioassays are useful tools for screening sensitization potency of allergic chemicals, and the toxicity enhancement (Te) can be used to discriminate sensitizers from weak or nonsensitizers. However, in this context we should separate aromatic from aliphatic Mas (Michael acceptors). Moreover, metabolic biotransformation should be considered during predicting nonsensitizers’ skin sensitization. 2. Chemical reactivity of selected 55 compounds measuring through kinetic glutathione chemoassay applies to predict their skin sensitization. This chemoassay confirms the fact that the key step of sensitizers eliciting skin sensitization is formatting a covalent adduct between sensitizers and skin proteins or peptides. The chemical reactivity of tested sensitizers strongly relates with their sensitization potential, with strong (extreme) sensitizers presenting the highest reactivity as followed with moderate sensitizers, weak sensitizers as well as nonsensitizers. Moreover, an integrated platform of this chemoassay data and three bioassays data is performed, and this performance shows good sensitivity for monitoring skin sensitization potency, with more rational accuracy for each sensitizing classifications. 3. Thiol reactivity (kGSH) as well as toxicity enhancement (Te) of additional 21 aliphatic α,β-unsaturated compounds are determined for predicting their skin sensitization potential. The linear regressions of skin sensitization versus thiol reactivity and skin sensitization versus toxicity enhancement are significantly improved after classifying these 21 compounds to four chemical subgroups (acrylates, other esters, ketones and aldehydes). Thiol reactivity of these subgroups presented different sensitivity to skin sensitization, with a decreasing order as acrylates (－2.05) > other esters (－1.26) > ketones (－0.43) > aldehydes (－0.21). Moreover, thiol reactivity is confirmed to be a more sensitive tool for predicting skin sensitization, compared with toxicity enhancement. Although the datasets are probably too small to give a definite decision, hydrophobicity reveals contribution to skin sensitization for aliphatic MAs, which is different with literature report. This study suggests that aliphatic MAs should be treated separately into different chemical subgroups for analysis, and their skin sensitization potency can be predicted using kinetic glutathione chemoassay as well as toxicity enhancement bioassay.

Orientador: Luís Otávio Zanatta Sarian / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-27T18:24:57Z (GMT). No. of bitstreams: 1 Matheus_CarolinaNascimben_D.pdf: 2850729 bytes, checksum: fd170a425e039c6e8f1324b637393c8b (MD5) Previous issue date: 2015 / Resumo: Objetivo: Esta tese visou avaliar os parâmetros vasculares arteriais e venosos dos vasos axilares e braquiais em mulheres submetidas a tratamento para câncer de mama. Subdividimos estas avaliações conforme os objetivos abordados em duas publicações, respectivamente: 1) Comparar aos parâmetros de circulação venosa e arterial nos vasos axilares e braquiais em função do tipo de abordagem cirúrgica da axila (BLS ou LAT) em até seis meses após a intervenção. 2) Identificar os fatores que influenciam os parâmetros vasculares da veias axilares e braquiais ipsilaterais à cirurgia para tratamento do câncer de mama. Métodos: Foram identificadas 547 pacientes consecutivas, submetidas a tratamento cirúrgico para câncer de mama entre agosto de 2012 e janeiro de 2014. Depois de seguir critérios de inclusão e exclusão, 197 mulheres foram recrutadas. O projeto foi aprovado pelo comitê de ética do hospital e todos os pacientes assinaram o termo de consentimento informado. Os critérios de inclusão foram 1) câncer da mama primário operável 2) abordagem axilar cirúrgica; 3) não ter sido submetida a reconstrução da mama. Os critérios de exclusão foram 1) câncer de mama bilateral, 2) história prévia de procedimentos cirúrgicos para um dos membros superiores ou no tórax, 3) comprometimento ortopédico ou neurológico de um dos membros superiores, 4) insuficiência renal ou cardíaca. Todas as pacientes responderam a um breve questionário sobre suas características clínicas e epidemiológicas. Foi então realizada avaliação ultrassonográfica dos vasos braquiais e axilares, bilateralmente, nos seguintes momentos: no dia anterior à cirurgia e 1, 3, 6 e 12 meses após a cirurgia. No primeiro artigo, comparamos os parâmetros arteriais e venosos, até seis meses após a cirurgia, em função da realização de dissecção linfática completa ou linfonodo sentinela; no segundo, restringimos as análises ao sistema venoso e estendemos a avaliação para até 1 ano após a cirurgia, comparando os parâmetros vasculares em função de características clínicas e epidemiológicas das pacientes e das modalidades de tratamentos utilizados. Resultados: Foram encontradas restrições de diâmetro em veias do braço ipsilateral ao câncer de mama de mulheres submetidas à dissecção axilar (LAT), efeito que não foi observado no grupo BLS. A área da secção transversal de veias braquial e axilar diminuiu progressivamente até seis meses, com a redução do fluxo sanguíneo concomitante destes vasos. Encontramos, na mulher sem linfedema, que a área de secção transversal e fluxo venoso do sangue (especialmente veia braquial) são negativamente afetados pela cirurgia e / ou quimioterapia / radioterapia. Este efeito prejudicial parece persistir até um ano. Não houve diferença significativa em nenhum dos parâmetros estudados entre os vasos ipsi e contralaterais ao câncer de mama. Conclusões: De maneira geral, nosso estudo demonstra que os tratamentos cirúrgicos, especialmente LAT, e a radio e quimioterapia, possuem efeitos deletérios sobre a circulação sanguínea dos vasos axilares e braquiais, sobretudo venosos. Esses efeitos são aparentemente permanentes e há necessidade de extensão do tempo de follow-up a fim de avaliar se o desenvolvimento subsequente de linfedema ocorrerá em associação às alterações vasculares / Abstract: Objective: The aim of this thesis was to evaluate the arterial and venous vascular parameters of the axillary and brachial vessels in women who underwent treatment for breast cancer. We subdivided these assessments according to the following objectives, in two publications: 1) To compare the venous and arterial vascular parameters in the axillary vessels and brachial depending on the type of axillary surgical approach (SLNB or ALND) within six months after the intervention. 2) To identify which factors influence the vascular parameters of axillary and brachial veins ipsilateral to surgical for treatment of breast cancer. Methods: We identified 547 consecutive patients undergoing surgical treatment for breast cancer between August 2012 and January 2014. After following inclusion and exclusion criteria, 197 women were recruited. The project was approved by the hospital's ethics committee and all patients signed an informed consent form. Inclusion criteria were 1) primary operable breast cancer 2) surgical axillary approach; 3) not having undergone breast reconstruction. Exclusion criteria were 1) bilateral breast cancer, 2) history of previous surgical procedures for one of the upper limbs or breast, 3) orthopedic or neurological impairment of one upper limb, 4) kidney or heart failure. All patients completed a brief questionnaire about their clinical and epidemiological characteristics. Then we performed Doppler ultrasonography evaluation of axillary and brachial vessels, bilaterally, at the following times: the day before surgery and 1, 3, 6 and 12 months after surgery. In the first article, we compared the arterial and venous parameters, up to six months after surgery, depending on SLNB or ALND; in the second, we restricted the analysis to the venous system and extend the evaluation for up to 1 year after surgery, comparing the vascular parameters with clinical and epidemiological characteristics of patients and treatment modalities used. Results: diameter restrictions were found in the ipsilateral veins of the arm in women with breast cancer undergoing ALND, and that effect was not observed in SLNB group. The cross sectional area of brachial and axillary veins progressively decreased up to six months, with concomitant reduction of blood flow to these vessels. In women with no lymphedema, the cross-sectional area and venous blood flow (especially brachial vein) are negatively affected by surgery and / or chemotherapy / radiotherapy. This detrimental effect seems to persist up to one year. There was no significant difference on studied parameters between ipsilateral and contralateral vessels to breast cancer. Conclusions: In essence, our study shows that surgical treatments, especially ALND, and the radiation and chemotherapy, have deleterious effects on blood circulation of the axillary and brachial vessels, especially venous. These effects are apparently permanent, prompting the extension of the follow-up evaluation in order to assess whether subsequent lymphedema formation will be associated with vascular abnormalities / Doutorado / Oncologia Ginecológica e Mamária / Doutora em Ciências da Saúde

No description available.

Ziel einer Definition der Resektabilität von Pankreaskarzinomen ist die Beschreibung von Kriterien, welche eine potentielle R0-Resektion ermöglichen. Wenngleich es zur Frage der Resektion bei positiven regionären Lymphknoten keine kontrollierten Studien gibt, ist weltweit die Resektion bei regionären Lymphknotenmetastasen Standard. Positive interaortokavale Lymphknoten stellen trotz Klassifikation als Fernmetastasen (M1) keine absolute Kontraindikation zur Resektion dar. Die mesenteriko-portale Venenresektion bei Verdacht auf Tumorinfiltration ist ein sicheres Verfahren. Sie hat keinen negativen Einfluss auf Morbidität, Mortalität und Überleben. Die En-bloc-Resektion der Arteria hepatica und der Arteria mesenterica superior wird sehr kontrovers diskutiert und sollte nur in Einzelfällen erwogen werden. Bei den meist fortgeschrittenen Karzinomen des Pankreaskorpus und -schwanzes kann durch eine En-bloc-Resektion des Truncus coeliacus eine höhere R0-Resektionsrate erreicht werden. / Pancreatic Cancer: Criteria and Limits of Resectability The aim of defining the resectability of pancreatic cancer is to determine the indication for potential R0 resection. Despite the absence of controlled trials, tumor resection in patients with regional lymph node involvement is a standard procedure worldwide. The involvement of interaortocaval lymph nodes is not an absolute contraindication for resection, although they are classified as distant metastasis (M1). Major pancreatic surgery can be safely combined with en-bloc resection of mesenteric, portal and splenic veins. Postoperative morbidity and mortality and long-term survival in patients with vein resection are comparable with those of patients without vein resection. The role of arterial en-bloc resection of the hepatic artery and the superior mesenteric artery is highly controversial and should be considered only in selected patients. For patients with locally advanced cancer of the body and tail of the pancreas distal pancreatectomy with en-bloc celiac axis resection offers an improved R0 resection rate. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

No description available.

A avaliação de linfonodos é parte importante do estadiamento das neoplasias mamárias, muito comum em cadelas, podendo auxiliar no estabelecimento do prognóstico e na escolha da melhor conduta terapêutica. Neste trabalho, dentre as várias técnicas de exame que permitem a avaliação de linfonodos, foi utilizada a ultra-sonografia. A avaliação ultra-sonográfica em modo B possibilitou avaliar tamanho, contorno, borda, forma, arquitetura, ecotextura e ecogenicidade do parênquima dos linfonodos e, em modo Doppler, a quantidade e distribuição dos seus vasos internos. Os objetivos deste trabalho foram identificar as características ultra-sonográficas mais importantes utilizadas para classificar os linfonodos em metastáticos e não-metastáticos, estabelecer elementos de confiabilidade do ultra-som como ferramenta para diferenciar linfonodos metastáticos de não-metastáticos e estabelecer procedimentos que permitam ao exame ultra-sonográfico de linfonodos, para essa classificação, ser reprodutível. Foram examinados 63 linfonodos inguinais superficiais de 30 cadelas com tumor em pelo menos uma das mamas inguinais ou abdominais caudais. Após o exame, cada linfonodo foi classificado como metastático ou não-metastático. A impressão diagnóstica do exame ultra-sonográfico foi associada aos resultados do exame histopatológico dos linfonodos obtendo-se uma taxa de concordância de 92,5%, índice de sensibilidade de 94,1%, índice de especificidade de 92%, valor preditivo positivo de 0,8 e valor preditivo negativo de 0,9787. As principais características ultra-sonográficas que classificaram um linfonodo inguinal superficial como metastático foram o contorno irregular, forma arredondada com razão C/E menor que dois, arquitetura desorganizada, ecotextura homogênea ou heterogênea, ecogenicidade alterada, vascularização elevada e de localização periférica. Quanto aos linfonodos não-metastáticos, as principais características ultra-sonográficas identificadas foram contorno regular, forma ovalada com razão C/E maior que dois, arquitetura preservada, ecotextura preservada, ecogenicidade normal, vascularização discreta a pequena e de localização hilar. O exame ultra-sonográfico dos linfonodos regionais constitui importante ferramenta na detecção de metástase e sugere-se incluí-lo como rotina do estadiamento de neoplasias mamárias em cadelas. / The evaluation of lymph nodes is an important part of the staging in case of mammary tumors, which are very common in female dogs. It can help in establishing a prognosis and chosing the best therapeutic procedures. In this study we used ultrasonography to assess lymph nodes within a variety of imaging techniques. B mode ultrasonography was used to provide information on size, edge, nodal borders, shape, architecture, echotexture and echogenivity of lymph nodes and Doppler ultrasonography to evaluate the quantity and distribution of the intranodal vessels. The objectives of this work were to identify which features in an ultrasound image can be associated to the metastatic or non-metastatic character of a lymph node; to establish the accuracy of the ultrasound as a tool to differentiate between metastatic and non-metastatic behavior and to establish procedures that permit the reproducibility of the results. Sixty three lymph nodes in thirty female dogs with mammary tumors were examined. We chose female dogs that had involvement of at least one of the inguinal or caudal abdominal mammary glands. Ultrasound imaging and histopathological exams were performed for each lymph node. Based on its ultrasound imaging, each lymph node was classified as metastatic or non-metastatic. When the ultrasound diagnostic was matched to the results of the histopathologic exam it was found that the classification of the lymph nodes using ultrasound imaging was correct in 92.5% of the cases, with sensibility of 94.1%, specificity of 92%, positive predictive value of 0.8 and negative predictive value of 0.9787. The main features in an ultrasound image associated with a metastatic superficial inguinal lymph node were irregular edge, round shape with long to short axis ratio lower than 2, loss of internal structure, homogeneous or heterogeneous echotexture, alteration of the echogenicity and high and peripheral vascularity. Relating to non metastatic lymph nodes, the main ultrasonographic characteristics were regular edge, oval shape with long to short axis ratio higher than 2, maintenance of internal structure, normal echo genetics and low hilar vascularity. The ultrasound imaging of regional lymph nodes is an important tool to detect metastasis and it is suggested that it becomes a regular procedure in the staging of canine mammary tumors.

INTRODUÇÃO: O câncer gástrico precoce que invade a submucosa pode apresentar acometimento linfonodal em torno de 20% dos casos. O tratamento cirúrgico clássico com gastrectomia e linfadenectomia D2 é um procedimento não isento de mortalidade e morbidade. Determinar quais pacientes têm maior risco de acometimento linfonodal permitiria tratamentos com menores complicações. Recentemente diversos autores relatam maior expressão imuno-histoquímica de p53 e p21ras em tumores avançados e com pior prognóstico. Tem sido relatada também perda da expressão de p21waf1, p27kip1 e p16ink4a nos tumores avançados e algumas publicações relatam também relação entre a expressão dos marcadores e acometimento linfonodal. MÉTODOS: Foram estudados retrospectivamente 81 pacientes submetidos à gastrectomia com linfadenectomia D2 no período de 1971 a 2004 no Serviço de Cirurgia do Estômago e Intestino Delgado do Departamento de Gastroenterologia do HC-FM/USP. Os blocos de parafina contendo fragmentos dos tumores foram recuperados e novo exame histopatológico confirmou o diagnóstico. Selecionaram-se áreas representativas de mucosa normal, mucosa metaplásica e tumor para confecção de novos blocos de tissue microarrays. Foi avaliada a expressão imuno-histoquímica de p21ras, p53, p21waf1/cip1, p27kip1 e p16ink4a nos tecidos. Foram investigadas as correlações entre a expressão dos marcadores e as características clínico-patológicas dos pacientes. A análise da associação entre os dados clínicos e a positividade dos marcadores foi realizada pelo teste Qui-quadrado. RESULTADOS: Na mucosa normal, metaplásica e tumoral p53 apresentou positividade em 53%, 87,3% e 87,1% dos casos respectivamente. Nos mesmos tecidos p21ras apresentou positividade de 85,3%, 86% e 96,8%. Para p16ink4a a positividade foi de 46,3%, 91,1% e 86%. Para p27kip1 a positividade foi de 60%, 94,7% e 95,3%. Para p21waf1/cip1 a positividade foi 32,4%, 72,7% e 71,4%. Todos os tumores tiveram alguma positividade para p53. Os tumores com acometimento linfonodal apresentaram hiper-expressão(+4) de p53 em 47% dos casos contra 17% nos pacientes que não tinham acometimento. Nenhum tumor com positividade para p53 baixa(0 e +1) teve linfonodos acometidos. Nenhum tumor com p21ras negativo apresentou linfonodos acometidos. Nos pacientes com acometimento linfonodal p21ras teve positividade intensa(+2 e +3) em 88% dos casos contra 50% dos casos sem acometimento linfonodal. Houve positividade intensa(+2,+3 e +4) de p21waf1/cip1 em 71% dos tumores com acometimento linfonodal contra 28% nos pacientes sem acometimento. Não observamos perda de expressão de p21waf1, p27kip1 e p16ink4a nos tumores com acometimento linfonodal. Na mucosa normal p16ink4a foi hiper-expresso (+4) em 20% dos casos com infiltração perineural contra 0% nos casos sem acometimento. O mesmo marcador foi hiperexpresso em 50% dos casos com infiltração vascular contra 0% dos casos sem infiltração. Os tumores com padrão de infiltração Sm2 tiveram pouca positividade(0 e +1) de p27kip1 na mucosa normal em 89% dos casos contra 55% dos casos Sm1. CONCLUSÕES: Maior expressão de p53, p21ras e p21waf1/cip1 no tumor teve relação estatística significante com acometimento linfonodal. Ocorre aumento da expressão imuno-histoquímica de todos os marcadores da mucosa normal para o tumor. A maior hiper-expressão de p16ink4a na mucosa normal de pacientes tem relação com infiltração perineural e vascular nos tumores. A expressão dos marcadores é diferente nas raças estudadas. As pacientes do sexo feminino apresentam maior positividade de p21waf1 na mucosa normal. Pacientes com história familiar de câncer gástrico apresentam maior positividade de p16ink4a na mucosa normal, menor positividade de p21waf1/cip1 e p21ras na mucosa metaplásica. Maior positividade na mucosa normal de p21waf1/cip1 relaciona-se a sexo feminino e infiltração tipo Sm1 / INTRODUCTION: Early gastric cancer that invades the submucosa might have a lymphonodal involvement in about 20% of the cases. Gastrectomy and D2 linfadenectomy is a procedure that has presented mortality and morbidity. Determining which patients would have a greater risk of lymphonodal involvement would allow treatments with fewer complications. Recently, several authors reported a greater immunohistochemical expression of p53 and p21ras in advanced tumors with worst prognosis. It has also been reported the expression loss of p21wafl, p27kip1, and p16ink4a in advanced tumors, and, some studies also observed the relationship between the markers expression and lymphonodal involvement. METHODS: Eightyone patients who had undergone gastrectomy with D2 linfadenectomy from 1971 to 2004 were retrospectively studied. A new histopathological exam confirmed the diagnosis. Representative areas of both normal and metaplastic mucosa and of the tumor were selected for obtaining new blocks of tissue microarrays. The immunohistochemical expression of p21ras, p53, p21waf1/cip1, p27kip1 and p16ink4a in the tissues was evaluated. RESULTS: In normal, metaplastic and tumoral mucosa, p53 showed positivity in 53%, 87.3%, and 87.1% of the cases, respectively. In the same tissues, p21ras showed positivity in 85.3%, 86%, and 96.8%, respectively. The positivity of p16ink4a was 46.3%, 91.1%, and 86%, respectively. p27kip1 showed a positivity of 60%, 94.7%, and 95.3%, respectively. p21wafl/cip1 presented a positivity of 32.4%, 72.7%, and 71.4%, respectively. All tumors showed positivity for p53. Tumors with lymphonodal involvement presented hyperexpression (+4) of p53 in 47% of the cases versus 17% in patients who had not showed any involvement. No tumor with low positivity (0 and +1) of p53 showed lymphonodal involvement. No tumor with negative p21ras showed lymphonodal involvement. In patients with lymphonodal involvement, p21ras presented strong positivity (+2 and +3) in 88% of the cases versus 50% of the cases without lymphonodal involvement. There was a strong positivity (+2,+3, and +4) of p21wafl/cip1 in 71% of the tumors with lymphonodal involvement versus 28% in patients without involvement. It was not observed an expression loss of p21waf1, p27kip1 e p16ink4a in tumors with lymphonodal involvement. In normal mucosa, p16ink4a showed a hyper-expression (+4) in 20% of the cases with perineural invasion versus 0% of the cases without invasion. This same marker showed a hyper-expression in 50% of the cases with vascular invasion versus 0% of the cases without invasion. Tumors with Sm2 invasion pattern showed low positivity (0 and +1) of p27kip1 in normal mucosa in 89% of the cases versus 55% of the cases of Sm1 tumors. CONCLUSIONS: Higher expression of p53, p21ras, and p21wafl/cip1 in tumor showed a significant statistical relationship with lymphonodal involvement. A higher hyper-expression of p16ink4a in patients normal mucosa was related to perineural and vascular invasion of tumors