Prognostic models have clinical appeal to aid therapeutic decision making. In the UK, the Nottingham Prognostic Index (NPI) has been used, for over two decades, to inform patient management. However, it has been commented that NPI is not capable of identifying a subgroup of patients with a prognosis so good that adjuvant therapy with potential harmful side effects can be withheld safely. Tissue Microarray Analysis (TMA) now makes possible measurement of biological tissue microarray features of frozen biopsies from breast cancer tumours. These give an insight to the biology of tumour and hence could have the potential to enhance prognostic modelling. I therefore wished to investigate whether biomarkers can add value to clinical predictors to provide improved prognostic stratification in terms of Recurrence Free Survival (RFS). However, there are very many biomarkers that could be measured, they usually exhibit skewed distribution and missing values are common. The statistical issues raised are thus number of variables being tested, form of the association, imputation of missing data, and assessment of the stability and internal validity of the model. Therefore the specific aim of this study was to develop and to demonstrate performance of statistical modelling techniques that will be useful in circumstances where there is a surfeit of explanatory variables and missing data; in particular to achieve useful and parsimonious models while guarding against instability and overfitting. I also sought to identify a subgroup of patients with a prognosis so good that a decision can be made to avoid adjuvant therapy. I aimed to provide statistically robust answers to a set of clinical question and develop strategies to be used in such data sets that would be useful and acceptable to clinicians. A unique data set of 401 Estrogen Receptor positive (ER+) tamoxifen treated breast cancer patients with measurement for a large panel of biomarkers (72 in total) was available. Taking a statistical approach, I applied a multi-faceted screening process to select a limited set of potentially informative variables and to detect the appropriate form of the association, followed by multiple imputations of missing data and bootstrapping. In comparison with the NPI, the final joint model derived assigned patients into more appropriate risk groups (14% of recurred and 4% of non-recurred cases). The actuarial 7-year RFS rate for patients in the lowest risk quartile was 95% (95% C.I.: 89%, 100%). To evaluate an alternative approach, biological knowledge was incorporated into the process of model development. Model building began with the use of biological expertise to divide the variables into substantive biomarker sets on the basis of presumed role in the pathway to cancer progression. For each biomarker family, an informative and parsimonious index was generated by combining family variables, to be offered to the final model as intermediate predictor. In comparison with NPI, patients into more appropriate risk groups (21% of recurred and 11% of non-recurred patients). This model identified a low-risk group with 7-year RFS rate at 98% (95% C.I.: 96%, 100%).

Mūsų darbo tikslas buvo ištirti naviko proliferacijos žymens Ki-67 prognozinę ir prediktyvinę reikšmę bei imunologinius pokyčius neišplitusia melanoma sergantiems pacientams Pacientai ir metodai: Tiriant Ki-67 žymens prognozinę ir prediktyvinę reikšmę, retrospektyviai buvo ištirti 80 pacientų, kuriems buvo nustatyta neišplitusi melanoma su naviko storiu ≥ 1,5 mm. Vykdant prospektyvinį tyrimą, buvo išanalizuoti imunologiniai duomenys 27 pacientų, kuriems buvo nustatyta neišplitusi melanoma (pTis-pT4N0M0). Melanoma sergančių pacientų imunologiniai rodikliai buvo palyginti su 39 kontrolinės grupės asmenų atitinkamais rodikliais. Rezultatai: Ki-67 žymuo neturėjo prognozinės reikšmės negydytiems IFN-α melanoma sergantiems pacientams, su naviko storių ≥ 1,5 mm. Tuo tarpu gydytų IFN-α pacientų su Ki-67<16% išgyvenimas buvo ilgesnis negu pacientų su Ki-67 ≥ 16% (p=0,016). Tiriant imunologinius parametrus buvo nustatyta, kad melanoma sergančių pacientų periferiniame kraujyje yra mažiau monocitų (p=0,0002) ir citotoksinių T limfocitų CD8highCD57- (p=0,009). Sergantys neišplitusia melanoma pacientai periferiniame kraujyje turi reikšmingai daugiau CD4+ (p=0,02) ir CD8low (p=0,04) limfocitų. Išvados: Ki-67 proliferacijos žymuo neturi prognozinės reikšmės neišplitusia melanoma sergantiems pacientams, ir įgyja prediktyvinę reikšmę gydytiems IFN-α pacientams. Neišplitusia melanoma sergantiems pacientams stebimi reikšmingi imunokompetentinių ląstelių pokyčiai periferiniame kraujyje. / The aim of the study was to explore the prognostic and predictive significance of proliferative index Ki-67 and changes of imunological parameters in non-metastatic melanoma patients MATERIALS AND METHODS: To explore the prognostic and predictive significance of the proliferative index Ki-67, a retrospective analysis was performed with 80 patients, in whom primary non-metastatic melanoma with tumour thickness of ≥ 1,5 mm was diagnosed. A prospective study was performed to explore the immunological parameters in 27 patients who had been diagnosed with non-metastatic melanoma (pTis-pT4N0M0). The immunologic parameter values of patients were compared with those of the control group (39 subjects). RESULTS: Proliferative index Ki-67 in primary tumours had no significant prognostic value in melanoma patients non-treated with IFN-α, tumour thickness≥ 1.5 mm. However, survival of IFN-α treated non-metastatic melanoma patients with Ki-67 expressed in <16% cells was longer than that of the patients with Ki-67 expressed in ≥ 16% cells (p=0,016). The investigation of immunological parameters showed that the peripheral blood of melanoma patients contained a smaller amount of monocytes (p=0.0002) as well as cytotoxic T lymphocytes CD8highCD57- (p=0,009) compared to healthy controls (p=0.009). Patients had significantly higher counts of CD4+ (p=0.02) and CD8low (p=0.04) lymphocytes compared to healthy controls. CONCLUSIONS: Ki-67 proliferative index has no prognostic significance and... [to full text]

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL). FL is clinically designated as an indolent disease with a long median survival of 8-10 years. However, the clinical and biological behavior of FL shows considerable variability, with some patients showing aggressive disease progression and very short survival. Because defects in the regulation of apoptotic cell death are fundamental in FL pathogenesis, we hypothesized that deregulated expression of components of the pRb signaling pathway may promote cell proliferation, thereby complementing antecedent anti-apoptotic mutations and producing more aggressive disease. In the present study we undertook an immunohistochemical (IHC) evaluation of expression of key cell-cycle regulatory proteins in diagnostic biopsies from 127 cases of FL using formalin-fixed, paraffin-embedded tissues (FFPE) in tissue microarray (TMA) sections immunostained for p53, pRb, p16INK4A and cyclin D3. Data analysis revealed that increased abundance of p53 or p16INK4A is associated with reduced overall survival (OS) (p=0.005 and p=0.014 respectively), and with conventional pathological markers of tumour aggressiveness including high histologic grade. Encouraged by this remarkable finding of a counterintuitive association between p16INK4A expression and clinical outcome, we analyzed CDKN2A gene deletion and methylation, as these are the most frequent mechanisms of the CDKN2A gene inactivation in NHL including FL. We determined the deletion and methylation status of CDKN2A in 105 FL cases. Laser-capture microdissection was used to enrich the samples for lymphoma cells. CDKN2A was deleted in 9 cases and methylated in 22 cases. The 29 cases (28%) with CDKN2A deletion or methylation had decreased overall survival (OS) (p=0.046) in all cases and in cases treated with rituximab (p<0.001). Our findings indicate that deleterious alterations of CDKN2A are relatively prevalent in FL at diagnosis and can predict poor clinical outcome. In summary, our data reveal novel insights into the pathogenesis of FL and suggest a relationship between increased p16INK4A expression and CDKN2A deletion or methylation and unfavorable clinical outcome in FL. We hope that the work presented herein will provide a useful prognostic tool for predicting the prognosis and choosing optimal treatment approaches to help patients suffering from FL. / Thesis (Ph.D, Pathology & Molecular Medicine) -- Queen's University, 2013-03-12 23:49:44.541

Thulani Nyathi, Student no: 0413256X, MSc thesis, Physics, Faculty of science. 2006. Supervisor: Prof D van der Merwe. / This study aims to calculate tumour control probabilities (TCP) and normal tissue complication probabilities (NTCP) using radiobiological models and correlate these probabilities with clinically observed treatment outcome from follow-up records. These radiobiological calculations were applied retrospectively to thirty-nine paediatric patients who were treated with radiation at Johannesburg Hospital during the period January 1990 to December 2000 and had histologically proven rhabdomyosarcoma. Computer software, BIOPLAN, was used to calculate the TCP and NTCP arising from the dose distribution calculated by the treatment planning system and characterized by dosevolume histograms (DVHs). There was a weak correlation between the calculated TCP and the observed 5-year overall survival status. Furthermore, potential prognostic factors for survival were examined. Statistical analysis was performed using the Cox proportional hazards regression model. The 5-year overall survival rate was 55 %. The findings of this study are a yardstick against which more aggressive radiotherapy fractionation regimes can be compared.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Medicine in the branch of Psychiatry Melbourne, 2005 / Sexual dysfunction is a common side effect of treatment with antidepressants, particularly those with a serotonergic action. The problem has significant implications for a patient’s quality of life and their compliance with medication. Given the often longterm nature of depressive disorders and their treatment this side effect poses a potential management challenge and may have serious prognostic implications. There are currently few evidence-based treatment strategies for the management of antidepressant induced sexual dysfunction. This study was conducted to evaluate the usefulness of granisetron, a serotonin type-3 receptor antagonist, in the treatment of women experiencing sexual dysfunction due to serotonergic antidepressants. Twelve women with antidepressant induced sexual dysfunction were assigned to receive either granisetron (N=5) or placebo (N=7) in a 14-day randomised, double blind, placebo controlled drug trial. Two subjects in the granisetron group did not complete the study. Each subject’s sexual functioning was assessed at baseline, day 7 and day 14 using both the Arizona Sexual Experience Scale and the Feiger Sexual Function and Satisfaction Questionnaire. No statistical differences were measured either at baseline or at endpoint between the granisetron and placebo groups. The study did not produce evidence supporting the usefulness of granisetron as an adjunctive medication in women with antidepressant induced sexual dysfunction. Furthermore, this finding does not suggest a primary role for the serotonin type-3 receptor in the pathogenesis of this side effect.

Le niveau de complexité croissant des systèmes et les exigences de performances et de sûreté de fonctionnement qui leur sont associées ont induit la nécessité de développer de nouvelles approches de surveillance. Les travaux de cette thèse portent sur la surveillance des systèmes complexes, notamment la détection, le diagnostic et le pronostic de défauts, avec une méthodologie basée sur la fusion de décisions. L’objectif principal est de proposer une approche générique de fusion de diverses méthodes de surveillance, dont la performance serait meilleure que celles des méthodes individuelles la composant. Pour cela, nous avons proposé une nouvelle démarche de fusion de décisions, basée sur la théorie Bayésienne. Cette démarche s’appuie sur une déduction théorique des paramètres du Réseau Bayésien en fonction des objectifs de performance à atteindre en surveillance. Le développement conduit à un problème multi-objectif sous contraintes, résolu par une approche lexicographique. La première étape se déroule hors-ligne et consiste à définir les objectifs de performance à respecter afin d’améliorer les performances globales du système. Les paramètres du réseau Bayésien permettant de respecter ces objectifs sont ensuite déduits de façon théorique. Enfin, le réseau Bayésien paramétré est utilisé en ligne afin de tester les performances de la fusion de décisions. Cette méthodologie est adaptée et appliquée d’une part à la détection et au diagnostic, et d’autre part au pronostic. Les performances sont évaluées en termes de taux de diagnostic de défauts (FDR) et taux de fausses alarmes (FAR) pour l’étape de détection et de diagnostic, et en durée de fonctionnement avant la défaillance du système (RUL) pour le pronostic. / Nowadays, systems are becoming more and more complex and require new effective methods for their supervision. This latter comprises a monitoring phase that aims to improve the system’s performances and ensure a safety production for humans and materials. This thesis work deals with fault detection, diagnosis and prognosis, with a methodology based on decisions fusion. The main issue concerns the integration of different decisions emanating from individual monitoring methods in order to obtain more reliable results. The methodology is based on a theoretical learning of the Bayesian network parameters, according to monitoring objectives to be reached. The development leads to a multi-objective problem under constraints, which is solved with a lexicographic approach. The first step is offline and consists of defining the objectives to be achieved in order to improve the overall performance of the system. The Bayesian network parameters respecting these objectives are then deduced theoretically. Finally, the parametrized Bayesian network is used online to test the decision fusion performances. These performances are evaluated in terms of Fault Diagnostic Rate (FDR) and False Alarm Rate (FAR) for the detection and diagnosis stage, and in terms of Remaining Useful Life (RUL) for the prognosis.

A neoplasia mamária é a doença mais entre as neoplasias em cadelas. As características clínicas dos tumores mamários caninos e sua relação com prognóstico foram discutidos, incluindo idade, raça, estagiamento clínico, diagnóstico histopatológico, hormônios e proliferação celular. Fatores clínicos prognósticos incluindo diâmetro do tumor e comprometimento linfonodal são discutidos em relação a graduação histopatológica e expressão de OCT4 (marcador para célula tronco tumoral). Avaliação imunohistoquímica dos marcadores (RE, RP, Ki-67 e OCT4) de neoplasias mamárias foi descritas. Foi observada marcação positiva para o OCT4, porém não se observou associação com fatores prognósticos clínicos. Assim como a marcação de RE, PR e Ki-67 foram observados. Houve uma forte associação entre graduação histopatológica de malignidade e tipo histológico. / Mammary neoplasms are the most common neoplasm in female dogs. The clinical features of canine mammary gland tumors and their relation to prognosis were discussed, including age, breed, staging, histopathological diagnosis, hormones, cell proliferation. Additional clinical prognostic factors including tumor size, and lymph node status are discussed in relation to graduation histopathological and OCT4 expression (cancer stem cell marker). Immunohistochemical evaluation of the markers (ER, PR, KI-67, OCT4) of the neoplastic canine mammary gland is described. We observed positive staining for OCT4, but was not associated with clinical prognostic factors. And the marking of ER, PR and Ki-67 was observed. There was a strong association between histopathological grade and histological type of malignancy.

Os melanomas correspondem a 7% de todas as neoplasias malignas em cães e são principalmente encontrados em cavidade oral e lábios, correspondendo a 33% dos tumores de boca, possuem um prognóstico ruim devido ao fato de serem diagnosticados tardiamente, por sua grande capacidade de invasão local e formação de metástases, além de altas taxas de recidiva após o tratamento cirúrgico. A Galectina-3 (Gal-3) é uma proteína responsável por diversas funções fisiológicas como adesão, apoptose, angiogênese, proliferação e diferenciação. Em medicina veterinária existem poucos estudos relacionando à expressão da Gal-3 com prognóstico e a progressão da neoplasia. Realizamos imuno-histoquímica para Gal-3 em 27 melanomas orais caninos que foram avaliados de maneira semiquantitativa e quantitativa, e comparamos os resultados obtidos com a sobrevida, outros marcadores prognósticos (Ki67, índice mitótico e atipia nuclear), expressão de proteínas relacionadas à apoptose (BCL2 e CASP3) e parâmetros histopatológicos (grau de pigmentação e tipo histológico). Detectamos alta expressão de Gal-3 em melanomas com maior sobrevida pós-cirúrgica e uma alta expressão nuclear de Gal-3 em melanomas com menor sobrevida pós-cirúrgica. Além disso, houve correlação entre as expressões de Gal-3 e BCL2, assim como entre atipia nuclear e sobrevida pós-cirúrgica. É sabido que a Gal-3 é capaz de formar heterodímeros com a BCL2 no citoplasma para atuar na evasão da morte por apoptose, impedindo a liberação da citocromo C. Já no núcleo, a Gal-3 induz à parada do ciclo celular, reduzindo a taxa da proliferação. Apesar do reduzido número amostral devido à dificuldade nos acompanhamentos clínicos nossos dados permitem sugerir que a Gal-3 é possui potencial para ser um marcador prognóstico de sobrevida em casos de melanomas orais caninos. Novos estudos devem ser realizados afim de confirmar nossas observações e elucidar o papel da Gal-3 nesta neoplasia. / Melanomas are almost 7% of all malignant neoplasms in dogs. They are mainly found in the oral cavity and lips, corresponding to 33% of tumors of the oral cavity. They carry a poor prognosis because of late diagnoses, local invasiveness, high metastatic and recurrence rates after surgical treatment. Galectin-3 (Gal-3) is a protein with a variety of biological roles such as in adhesion, apoptosis, angiogenesis, proliferation and differentiation. In veterinary medicine, there are few studies comparing the expression of Gal-3 with prognosis and tumor progression. We performed immunohistochemistry for Gal-3 in 27 canine oral melanomas and evaluated the immunolabelling both semi-quantitatively and quantitatively. The results were compared with survival, other prognostic markers (Ki67, mitotic index and nuclear atypia), expression of proteins related to apoptosis (BCL2 and CASP3) and histopathological parameters (degree of pigmentation and histological type). We detected higher expression of Gal-3 in cases of melanoma that presented longer post-surgical survival and a higher nuclear expression of Gal-3 in dogs with melanoma that had shorter post-surgical survival. In addition, there was correlation between the Gal-3 and BCL2 expressions, as well as between nuclear atypia and post-surgical survival. It is known that Gal-3 is able to form heterodimers with BCL2 in the cytoplasm leading to evasion of apoptosis, through preventing mitochondrial cytochrome C release. Nuclear Gal-3 induces the cell cycle arrest, reducing the proliferation rate. Despite the small sample size due to the difficulty in clinical follow-up, our data suggest that Gal-3 has the potential to be a prognostic marker for survival in cases of canine oral melanomas. Further studies should be performed to confirm our observations and elucidate the role of Gal-3 in this neoplasm.

Introdução: As diretrizes atuais recomendam classificar o risco de doentes com síndrome coronária aguda (SCA), visando a embasar decisões terapêuticas e para informar pacientes e equipe de saúde. Há diversos modelos prognósticos para pacientes com SCA, que, no entanto, podem ter limitações de calibração ou discriminação em função de terem sido elaborados há vários anos e em outras populações. Objetivo: Elaborar escores prognósticos para predição de eventos desfavoráveis em 30 dias e 6 meses, em população não selecionada portadora de SCA, com ou sem supradesnivelamento do segmento ST (SST), atendida em hospital privado terciário. Métodos: Trata-se de uma coorte prospectiva de pacientes recrutados consecutivamente de 1º de agosto de 2009 até 20 de junho de 2012. Definimos como desfecho primário composto a ocorrência de óbito por qualquer causa, infarto ou reinfarto não fatais, acidente vascular cerebral (AVC) não-fatal, parada cardiorrespiratória revertida e sangramento maior. As variáveis preditoras foram selecionadas a partir de dados clínicos, laboratoriais, eletrocardiográficos e da terapêutica. O modelo final foi obtido por meio de regressão logística e submetido à validação interna, utilizando-se técnica de bootstrap. A performance, calibração e discriminação do modelo final foram avaliadas com a estatística Brier escore, o teste de Hosmer-Lemeshow e a área sob a curva ROC (AROC), respectivamente. Resultados: A amostra de desenvolvimento dos escores foi de 760 pacientes, dos quais 132 com diagnóstico de SCA com SST e 628 com SCA sem SST. A média de idade foi de 63,2 anos (± 11,7), sendo 583 homens (76,7%). O modelo final para predição de eventos em 30 dias contém cinco variáveis preditoras: idade >=70 anos, antecedente de neoplasia, fração de ejeção do ventrículo esquerdo (FEVE) ?40%, valor de troponina I > 12,4ng/ml e trombólise química. O valor de P do teste de Hosmer-Lemeshow foi 0,72. Na validação interna, a estatística C foi de 0,71, e Brier escore, 0,06. O modelo final para predição de eventos em 6 meses é composto das seguintes variáveis: antecedente de neoplasia, FEVE <40%, trombólise química, troponina I >14,3ng/ml, creatinina >1,2mg/dl, antecedente de doença pulmonar obstrutiva crônica (DPOC) e hemoglobina <13,5g/dl. O valor de P do teste de Hosmer-Lemeshow foi 0,38. Na validação interna, a estatística C foi de 0,69, e Brier escore, 0,08. Conclusão: Desenvolvemos escores (Escores HCor) de fácil utilização e boa performance para predição de eventos adversos em 30 dias e 6 meses em pacientes com síndrome coronária aguda, com ou sem SST, atendidos em hospital terciário privado. / Introduction: Current guidelines recommend classifying the risk of acute coronary syndrome (ACS) with the aim of improving therapeutic decisions and better communicate prognosis to patients and healthcare personnel. There are several prognostic models for ACS patients. However, these may have limited calibration and discrimination as they were elaborated several years ago and using different populations. Objective: To develop prognostic scores for prediction of unfavorable events on 30 days and 6 months in an unselected population of ST-segment elevation ACS or non-ST-segment elevation ACS, admitted to a private tertiary hospital. Methods: We conducted a prospective cohort enrolling all eligible patients from August 1, 2009 to June 20, 2012. Our primary composite endpoint for both the 30-day and 6-month models was death from any cause, non-fatal myocardial infarction or re-infarction, non-fatal cerebrovascular accident (CVA), non-fatal cardiac arrest and major bleeding. Predicting variables were selected for clinical, laboratory, electrocardiographic and therapeutic data. We elaborated the final models using logistic regression, and used boostrap analysis for internal validation. We used Brier score, Hosmer-Lemeshow goodness-of-fit test and area under the ROC curve to assess global performance, calibration and discrimination, respectively. Results: We considered 760 patients for the development sample, of which 132 had ST-segment elevation ACS and 628 non-ST-segment elevation ACS. The mean age was 63.2 years (± 11.7), and 583 were men (76.7%). The final model to predict 30-day events is comprised by five independent variables: age >= 70 years, history of cancer, ejection fraction (LVEF) ? 40%, troponin I value of ?12.4 ng /ml and chemical thrombolysis. Hosmer-Lemeshow p-value was 0.72. In the internal validation analysis, C statistics was 0.71 and Brier score 0.06. The final model to predict 6-month events also includes history of of neoplasia, LVEF ? 40%, chemical thrombolysis, troponin >14.3 ng/ml, and three additional variables: creatinine ? 1.2 mg/dl, history of chronic obstructive pulmonary disease (COPD) and hemoglobin ? 13.5 g/dl. Hosmer-Lemeshow p-value was 0.38. In the internal validation analysis, C statistics was 0.69 and Brier score 0.08. Conclusion: We elaborated prognostic scores (HCor Score) of easy application and good performance for predicting adverse events in 30 days and 6 months for patients with ST-elevation and non-ST elevation ACS admitted to a tertiary private hospital.

Made available in DSpace on 2016-08-10T10:39:19Z (GMT). No. of bitstreams: 1 DEIDIMAR CASSIA BATISTA ABREU.pdf: 2392648 bytes, checksum: 56abc80b014df4ae449910b6f18afeae (MD5) Previous issue date: 2008-05-28 / In Brazil, breast cancer is the most incident tumor in the female population, and its natural history demonstrates variable clinical courses and different survival rates, according to each patient. Since the systemic therapy has an essential role in the treatment of breast cancer patients, the selection of those that will relapse became an important issue. Identification of significant prognostic factors is essential in therapeutic programs. Because it has been extensively reported that mutated p53 proteins are more stable its wild type counterpart, immunodetection of nuclear p53 protein in tumor cells became an indirect method used to analyze TP53 mutations. Immunodetection of nuclear p53 protein is considered a bad prognostic factor in a long list of human malignant tumors. This study analyze the imunodetection of p53 nuclear protein and its possible association with recognized prognostic factors in a group of 214 patients with breast cancer assisted at Hospital Araujo Jorge, in Brazil. In our study any association was demonstrated between p53 immunodetection and recognized clinical factors including: age over than 60 years old, clinical stage, tumor microscopic grade, immunodetection of estrogen and progesterone receptor, c-erbB-2, tumor size and nodal involvement. p53 immunodetection did not significantly influenced five years survival rates in the patients analyzed in our series. Similar results have been reported by different groups. We concluded that the more sensitive molecular methods must be evaluated, in order to validate the prognostic value of TP53 mutations in breast cancer. / No Brasil, o câncer de mama constitui-se na patologia maligna mais incidente na população feminina e a sua história natural demonstra um curso clínico e sobrevida variáveis. Desde que a terapia sistêmica tornou-se parte integrante do tratamento, a necessidade de saber se uma paciente terá maior ou menor probabilidade de recidiva loco-regional ou à distância tornou-se fundamental. O conhecimento de fatores prognósticos é de suma importância na determinação e eficácia dos programas terapêuticos. A imunodetecção da proteína p53 representa um método indireto de avaliar mutações no gene TP53 e tem sido descrita como fator prognóstico para inúmeras neoplasias malignas humanas e tem sido associada a um pior prognóstico das pacientes. Este estudo avaliou a imunodetecção nuclear da proteína p53 e sua associação com os fatores clínicopatológicos relativos ao paciente e ao tumor, em uma série de 214 pacientes portadoras de carcinoma de mama e atendidas no Hospital Araújo Jorge em Goiânia, no período de 1997-2001. Em nossa casuística a imunodetecção positiva de p53 nas células tumorais não demonstrou nenhuma associação com os parâmetros clínicopatológicos convencionais, incluindo: idade superior a 60 anos, estadiamento clínico, grau de anaplasia, expressão de receptores de estrogênio e/ou progesterona, c-erbB-2, comprometimento linfonodal e tamanho tumoral. A imunodetecção da proteína p53 não influenciou significativamente a sobrevida das pacientes analisadas em nossa série. Resultados semelhantes foram obtidos por outros estudos. Assim, concluímos que métodos moleculares mais sensíveis à detecção de mutações sejam testados, a fim de validar o papel prognóstico das mutações em TP53 no câncer de mama.