Oncoplastic Surgery: Does Patient and Medical Specialty Influences the Evaluation of Cosmetic Results?

BACKGROUND: Oncoplastic surgery (OS) has added plastic surgery concepts and techniques to the breast cancer surgery. However, reports of the impact of OS on cosmesis after breast-conserving surgery (BCS) are limited in the literature. PATIENTS AND METHODS: This cross-sectional prospective study included patients who underwent BCS. The patients self-evaluated the cosmetic outcome of the breasts and had them photographed. The photos were evaluated by BCCT.core software and by 6 breast surgeons (mastologists and plastic surgeons) using the Harvard, Garbay, and Fitoussi scales. Kappa and weighted kappa tests were used to analyze agreement for categorical variables; for continuous variables, the interclass correlation index and the chi-square test to analyze the association between the OS and the symmetrization. RESULTS: A total of 300 patients were evaluated: 228 (76.0%) underwent traditional BCS and 72 (24.0%) underwent OS, and of these, 37 (51.4%) underwent contralateral symmetrization surgery. In the evaluation of the cosmetic result, the correlation between patients and observers (BCCT.core and surgeons) was weak; between the 2 groups of surgeons, the correlation was moderate (Fitoussi scale) and excellent (Garbay scale). Plastic surgeons are more critical for evaluating cosmetic results; they considered it good or excellent in 30.0% whereas patients, mastologists, and BCCT.core results considered it so in 78.8%, 34.0%, and 30.0%, respectively. In terms of cosmesis, OS and symmetrization did not influence the results in this study with long follow-up. CONCLUSION: Patients' self-evaluation reported better cosmesis than surgeons' analyses. Plastic surgeons were the most critical. OS and symmetrization did not influence the results.

Lymphovascular invasion and histologic grade are associated with specific genomic profiles in invasive carcinomas of the breast.

Lymphovascular invasion (LVI) and histologic grade are clinical parameters of high prognostic value in breast cancer and indicate the level of tumor aggressiveness. Many studies have focused on the association of breast cancer subtypes with gene expression and chromosomal profiles, but considerably less genomic information is available regarding traditional prognostic factors such as histologic grade and LVI. We studied by array-CGH a group of 57 invasive ductal carcinomas of the breast to outline the DNA copy number aberration (CNA) profile linked to high histologic grades and LVI. Selected CNAs were validated using real-time quantitative PCR (qPCR). Furthermore, gene expression analysis was performed in a subset of 32 of these tumors, and findings were integrated with array-CGH data. Our findings indicated an accumulation of genomic alterations in high-grade breast tumors compared to low-grade samples. Grade III tumors showed higher number of CNAs and larger aberrations than low-grade tumors and displayed a wide range of chromosomal aberrations, which were mainly 5p, 8q, 10p, 17q12, and 19 gains, and 3p, 4, 5q proximal, 9p, 11p, 18q, and 21 losses. The presence of LVI, a well-established prognostic marker, was not significantly associated with increased genomic instability in comparison to breast tumors negative for LVI, considering the total number of chromosomal alterations. However, a slightly increase in the frequency of specific alterations could be detected in LVI-positive group, such as gains at 5p, 16p, 17q12, and 19, and losses at 8p, 11q, 18q, and 21. Three newly reported small-scale rearrangements were detected in high-risk tumors (LVI-positive grade III) harboring putative breast cancer genes (amplicons at 4q13.3 and 11p11.2, and a deletion at 12p12.3). Furthermore, gene expression analysis uncovered networks highlighting S100A8, MMP1, and MED1 as promising candidate genes involved in high-grade and LVI-positive tumors. In summary, a group of genomic regions could be associated with high-risk tumors, and expression analysis pinpointed candidate genes deserving further investigation. The data has shed some light on the molecular players involved in two highly relevant prognostic factors and may further add to the understanding of the mechanisms of breast cancer aggressiveness.

Validity, reliability and understanding of the EORTC-C30 and EORTC-BR23, quality of life questionnaires specific for breast cancer.

OBJECTIVE: To validate and assess reliability and understanding of the EORTC-C30 quality of life questionnaire and its breast cancer specific module, the EORTC-BR23. METHODS: This study was conducted at the AC Camargo Cancer Hospital, São Paulo, Brazil. A total of 100 women diagnosed with breast cancer were interviewed. Internal consistency, confirmatory factorial analysis, convergent validity, construct validity and degree of understanding were examined. Reliability was assessed by comparison of means at times 1 and 2, inter-class coefficient and Bland-Altman graphics. RESULTS: Cronbach's alpha ranged from 0.72 to 0.86 for the EORTC-C30 and from 0.78 to 0.83 for the EORTC-BR23 questionnaire. Most questions were confirmed in the confirmatory factorial analysis. In the construct validity analysis, the questionnaires were capable of differentiating patients with or without lymphedema, apart from the symptom scales of both questionnaires. Both questionnaires presented a significant correlation in most domains of the SF-36, in the convergent validity analysis. Only a few criticisms were reported concerning questions, and the mean grade of understanding was high (C30 = 4.91 and BR23 = 4.89). The questionnaires presented good rates of reliability, with the exception of the functional scale of the C30 and the symptom scale of the BR23. CONCLUSIONS: The EORTC-C30 and EORTC-BR23 quality of life questionnaires were validated, presented good rates of reliability and are easily understood, allowing them to be used in Brazil to assess quality of life among women with breast cancer.

Validity, reliability and understanding of the EORTC-C30 and EORTC-BR23, quality of life questionnaires specific for breast cancer / Validacao, reprodutibilidade e compreensao do EORTC-C30 e EORTC-BR23, questionarios de qualidade de vida especificos para cancer de mama

Objective: To validate and assess reliability and understanding of the EORTC–C30 quality of life questionnaire and its breast cancer specific module, the EORTC-BR23. Methods: This study was conducted at the AC Camargo Cancer Hospital, São Paulo, Brazil. A total of 100 women diagnosed with breast cancer were interviewed. Internal consistency, confirmatory factorial analysis, convergent validity, construct validity and degree of understanding were examined. Reliability was assessed by comparison of means at times 1 and 2, inter-class coefficient and Bland-Altman graphics. Results: Cronbach's alpha ranged from 0.72 to 0.86 for the EORTC-C30 and from 0.78 to 0.83 for the EORTC-BR23 questionnaire. Most questions were confirmed in the confirmatory factorial analysis. In the construct validity analysis, the questionnaires were capable of differentiating patients with or without lymphedema, apart from the symptom scales of both questionnaires. Both questionnaires presented a significant correlation in most domains of the SF-36, in the convergent validity analysis. Only a few criticisms were reported concerning questions, and the mean grade of understanding was high (C30 = 4.91 and BR23 = 4.89). The questionnaires presented good rates of reliability, with the exception of the functional scale of the C30 and the symptom scale of the BR23. Conclusions: The EORTC-C30 and EORTC-BR23 quality of life questionnaires were validated, presented good rates of reliability and are easily understood, allowing them to be used in Brazil to assess quality of life among women with breast cancer. .

Objetivos: Validar, analisar a reprodutibilidade e avaliar a compreensão do questionário de qualidade de vida EORTC-C30 e seu módulo específico para câncer de mama EORTC-BR23. Métodos: O estudo foi realizado no Hospital do Câncer AC Camargo, São Paulo, Brasil. Foram analisadas 100 mulheres com diagnóstico de câncer de mama. Para validação foi analisada a consistência interna, feita a análise fatorial confirmatória, a validade convergente, a validade de constructo e analisado o grau de compreensão. A reprodutibilidade foi verificada após 2 semanas e foi analisada mediante a comparação de médias, do coeficiente de correlação intraclasse e de gráficos de Bland-Altman. Resultados: O alfa de Cronbach para o C30 variou de 0,72 a 0,86 e do BR23 de 0,78 e 0,83. Na análise fatorial confirmatória a maioria das questões foi confirmada. Na análise da validade de constructo os questionários foram capazes de discriminar pacientes com ou sem linfedema, com exceção das escalas de sintomas. Na análise da validade convergente os questionários apresentaram correlação significativa com a maioria dos domínios do SF-36. Os questionários receberam poucas críticas quanto às questões e a média da nota de entendimento foi alta (C30 = 4,91 e BR23 = 4,89). Os questionários apresentaram bons índices de reprodutibilidade, com exceção da escala funcional do C30 e da escala de sintomas do BR23. Conclusões: Os questionários EORTC-C30 e EORTC-BR23 apresentaram bons índices de validade, de reprodutibilidade e de compreensão, permitindo o seu uso na avaliação da qualidade de vida de brasileiras com câncer de mama. .

Transcriptional effects of 1,25 dihydroxyvitamin D(3) physiological and supra-physiological concentrations in breast cancer organotypic culture.

BACKGROUND: Vitamin D transcriptional effects were linked to tumor growth control, however, the hormone targets were determined in cell cultures exposed to supra physiological concentrations of 1,25(OH)(2)D(3) (50-100nM). Our aim was to evaluate the transcriptional effects of 1,25(OH)(2)D(3) in a more physiological model of breast cancer, consisting of fresh tumor slices exposed to 1,25(OH)(2)D(3) at concentrations that can be attained in vivo. METHODS: Tumor samples from post-menopausal breast cancer patients were sliced and cultured for 24 hours with or without 1,25(OH)(2)D(3) 0.5nM or 100nM. Gene expression was analyzed by microarray (SAM paired analysis, FDR≤0.1) or RT-qPCR (p≤0.05, Friedman/Wilcoxon test). Expression of candidate genes was then evaluated in mammary epithelial/breast cancer lineages and cancer associated fibroblasts (CAFs), exposed or not to 1,25(OH)(2)D(3) 0.5nM, using RT-qPCR, western blot or immunocytochemistry. RESULTS: 1,25(OH)(2)D(3) 0.5nM or 100nM effects were evaluated in five tumor samples by microarray and seven and 136 genes, respectively, were up-regulated. There was an enrichment of genes containing transcription factor binding sites for the vitamin D receptor (VDR) in samples exposed to 1,25(OH)(2)D(3) near physiological concentration. Genes up-modulated by both 1,25(OH)(2)D(3) concentrations were CYP24A1, DPP4, CA2, EFTUD1, TKTL1, KCNK3. Expression of candidate genes was subsequently evaluated in another 16 samples by RT-qPCR and up-regulation of CYP24A1, DPP4 and CA2 by 1,25(OH)(2)D(3) was confirmed. To evaluate whether the transcripitonal targets of 1,25(OH)(2)D(3) 0.5nM were restricted to the epithelial or stromal compartments, gene expression was examined in HB4A, C5.4, SKBR3, MDA-MB231, MCF-7 lineages and CAFs, using RT-qPCR. In epithelial cells, there was a clear induction of CYP24A1, CA2, CD14 and IL1RL1. In fibroblasts, in addition to CYP24A1 induction, there was a trend towards up-regulation of CA2, IL1RL1, and DPP4. A higher protein expression of CD14 in epithelial cells and CA2 and DPP4 in CAFs exposed to 1,25(OH)(2)D(3) 0.5nM was detected. CONCLUSIONS: In breast cancer specimens a short period of 1,25(OH)(2)D(3) exposure at near physiological concentration modestly activates the hormone transcriptional pathway. Induction of CYP24A1, CA2, DPP4, IL1RL1 expression appears to reflect 1,25(OH)(2)D(3) effects in epithelial as well as stromal cells, however, induction of CD14 expression is likely restricted to the epithelial compartment.

Validação e reprodutibilidade do questionário FACT-B+4 de qualidade de vida específico para câncer de mama e comparação dos questionários IBCSG, EORTC-BR23 e FACT-B+4 / Validity and reliability of the FACT-B+4 quality of life questionnaire specific for breast cancer and comparison of IBCSG, EORTC-BR23 and FACT-B+4 questionnaires

O objetivo deste estudo foi validar, analisar a reprodutibilidade do questionário de qualidade de vida específico para câncer de mama FACT-B+4 e discutir a escolha do melhor questionário (IBCSG, EORTC-BR23 e FACT-B+4). O estudo foi realizado no Hospital do Câncer A.C. Camargo, São Paulo e 100 mulheres com diagnóstico de câncer de mama foram entrevistadas. Para a validação, foi analisada a consistência interna, feita a análise fatorial confirmatória, a validade convergente e a validade de constructo. A reprodutibilidade foi analisada através da comparação de médias, do coeficiente de correlação intraclasse e de gráficos Bland-Altman. A avaliação dos questionários baseou-se na confirmação da análise fatorial, na consistência interna, na validade de constructo, na validade convergente, na reprodutibilidade, no menor tempo médio de preenchimento e no maior grau de entendimento. O alfa de Cronbach para os domínios do FACT-B+4 variou de 0,38 a 0,82. Na análise fatorial confirmatória, todas as questões foram confirmadas. Na análise da validade de constructo, o questionário foi capaz de discriminar pacientes com ou sem linfedema (p=0,006). Na análise da validade convergente, o questionário apresentou correlação significativa com seis de oito domínios do SF-36. O questionário apresentou bons índices de reprodutibilidade. O questionário FACT-B+4 apresentou os parâmetros mais favoráveis.

Down-regulation of ANAPC13 and CLTCL1: Early Events in the Progression of Preinvasive Ductal Carcinoma of the Breast.

Alterations in the gene expression profile in epithelial cells during breast ductal carcinoma (DC) progression have been shown to occur mainly between pure ductal carcinoma in situ (DCIS) to the in situ component of a lesion with coexisting invasive ductal carcinoma (DCIS-IDC) implying that the molecular program for invasion is already established in the preinvasive lesion. For assessing early molecular alterations in epithelial cells that trigger tumorigenesis and testing them as prognostic markers for breast ductal carcinoma progression, we analyzed, by reverse transcription-quantitative polymerase chain reaction, eight genes previously identified as differentially expressed between epithelial tumor cells populations captured from preinvasive lesions with distinct malignant potential, pure DCIS and the in situ component of DCIS-IDC. ANAPC13 and CLTCL1 down-regulation revealed to be early events of DC progression that anticipated the invasiveness manifestation. Further down-regulation of ANAPC13 also occurred after invasion appearance and the presence of the protein in invasive tumor samples was associated with higher rates of overall and disease-free survival in breast cancer patients. Furthermore, tumors with low levels of ANAPC13 displayed increased copy number alterations, with significant gains at 1q (1q23.1-1q32.1), 8q, and 17q (17q24.2), regions that display common imbalances in breast tumors, suggesting that down-regulation of ANAPC13 contributes to genomic instability in this disease.

Comparison of postmenopausal endogenous sex hormones among Japanese, Japanese Brazilians, and non-Japanese Brazilians.

BACKGROUND: Differences in sex hormone levels among populations might contribute to the variation in breast cancer incidence across countries. Previous studies have shown higher breast cancer incidence and mortality among Japanese Brazilians than among Japanese. To clarify the difference in hormone levels among populations, we compared postmenopausal endogenous sex hormone levels among Japanese living in Japan, Japanese Brazilians living in the state of São Paulo, and non-Japanese Brazilians living in the state of São Paulo. METHODS: A cross-sectional study was conducted using a control group of case-control studies in Nagano, Japan, and São Paulo, Brazil. Participants were postmenopausal women older than 55 years of age who provided blood samples. We measured estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex hormone-binding globulin (SHBG) by immunoradiometric assay. A total of 363 women were included for the present analyses, comprising 185 Japanese, 44 Japanese Brazilians and 134 non-Japanese Brazilians. RESULTS: Japanese Brazilians had significantly higher levels of estradiol, bioavailable estradiol, estrone, testosterone and free testosterone levels, and lower SHBG levels, than Japanese. Japanese Brazilians also had significantly higher levels of bioavailable estradiol, estrone and DHEAS and lower levels of SHBG and androstenedione than non-Japanese Brazilians. Levels of estradiol, testosterone and free testosterone, however, did not differ between Japanese Brazilians and non-Japanese Brazilians. These differences were observed even after adjustment for known breast cancer risk factors. We also found an increase in estrogen and androgen levels with increasing body mass index, but no association for most of the other known risk factors. CONCLUSIONS: We found higher levels of estrogens and androgens in Japanese Brazilians than in Japanese and levels similar to or higher than in non-Japanese Brazilians. Our findings may help explain the increase in the incidence and mortality rate of breast cancer among Japanese Brazilians.

A multivariate analysis on prognostic factors for lobular carcinoma of the breast.

CONTEXT AND OBJECTIVE: Lobular carcinoma is the second most common type of breast neoplasia and has unique clinical and pathological features. Our aim was to evaluate prognostic factors for this type of breast cancer. DESIGN AND SETTING: Retrospective study at a tertiary oncological institution. METHODS: 162 patients diagnosed and treated between January 1985 and January 2002 were included. The inclusion criteria were: absence of previous treatment, histological diagnosis of lobular carcinoma, no previous history of breast cancer and minimum follow-up of 36 months. RESULTS: In univariate analysis, the following factors were statistically significant: clinical stage T (P = 0.0005), clinical stage N (P = 0.0014), neoadjuvant chemotherapy (P = 0.0008), primary tumor size (P < 0.0001), vascular invasion (P < 0.0001), lymphatic invasion (P = 0.0004), neural invasion (P = 0.0004), skin invasion (P < 0.0001), capsular transposition (P = 0.0008), lymph node ratio (P < 0.0001), estrogen receptor expression (P = 0.0186), progesterone receptor expression (P = 0.0286), pathological stage T (P < 0.0001), pathological stage N (P < 0.0001), adjuvant chemotherapy (P < 0.0001) and postoperative hormone therapy (P = 0.0367). After grouping the variables, multivariate analysis was performed. Presence of lymph node metastases, capsular transposition, lymph node ratio and postoperative hormone therapy remained significant. CONCLUSION: In this series, the most important prognostic factors for lobular carcinoma of the breast seemed to relate to lymph node status and presence of capsular transposition. Factors relating to axillary involvement, capsular transposition and hormone therapy were significant for survival.

Câncer de mama na gestação: relato de casos / Pregnancy-associated breast cancer: case reports

O câncer de mama na gestação vem se tomando uma realidade na medida em que a idade da primeira gestação das mulheres aumenta. Aproximadamente 3% dos tumores de mama são diagnosticados em mulheres grávidas entre os 23 e os 47 anos de idade (media de 33 anos). Por definição, o câncer de mama associado à gestação é todo câncer de mama diagnosticado durante a mesma ou até um ano após o parto. Em geral, o câncer de mama na gestação apresenta-se de forma avançada devido principalmente ao atraso no diagnóstico e no tratamento do que devido às características histológicas dos tumores. Na literatura, ainda não há um consenso sobre a melhor estratégia terapêutica a ser usada. São apresentados aqui três casos de câncer de mama durante a gestação bem como uma análise sobre aspectos patológicos, diagnósticos e terapêuticos, com base na experiência dos autores e no que há de mais recente na literatura.

Pregnancy-associated breast cancer is becoming a reality since women delay childbearing. Approximately 3% of breast cancers are diagnosed in pregnant woman between 23 to 47years (mean age 33 years). It is defined as any breast carcinoma diagnosed during pregnancy or during the first postpartum year. The pregnancy-associated breast cancer usually presents as an advanced stage, in part because of delay on diagnostic and treatment, than histological characteristics of the breast cancer. There is no consensus about the better treatment option that should being used. We report here three cases of pregnancy-associated breast cancer and discuss some clinical, histopathological, diagnostic and therapeutic aspects, showing our experience and the more recent we found in literature.

A multivariate analysis on prognostic factors for lobular carcinoma of the breast / Uma análise multivariada de fatores prognósticos para o carcinoma lobular de mama

CONTEXT AND OBJECTIVE: Lobular carcinoma is the second most common type of breast neoplasia and has unique clinical and pathological features. Our aim was to evaluate prognostic factors for this type of breast cancer. DESIGN AND SETTING:Retrospective study at a tertiary oncological institution. METHODS: 162 patients diagnosed and treated between January 1985 and January 2002 were included. The inclusion criteria were: absence of previous treatment, histological diagnosis of lobular carcinoma, no previous history of breast cancer and minimum follow-up of 36 months. RESULTS: In univariate analysis, the following factors were statistically significant: clinical stage T (P = 0.0005), clinical stage N (P = 0.0014), neoadjuvant chemotherapy (P = 0.0008), primary tumor size (P < 0.0001), vascular invasion (P < 0.0001), lymphatic invasion (P = 0.0004), neural invasion (P = 0.0004), skin invasion (P < 0.0001), capsular transposition (P = 0.0008), lymph node ratio (P < 0.0001), estrogen receptor expression (P = 0.0186), progesterone receptor expression (P = 0.0286), pathological stage T (P < 0.0001), pathological stage N (P < 0.0001), adjuvant chemotherapy (P < 0.0001) and postoperative hormone therapy (P = 0.0367). After grouping the variables, multivariate analysis was performed. Presence of lymph node metastases, capsular transposition, lymph node ratio and postoperative hormone therapy remained significant. CONCLUSION: In this series, the most important prognostic factors for lobular carcinoma of the breast seemed to relate to lymph node status and presence of capsular transposition. Factors relating to axillary involvement, capsular transposition and hormone therapy were significant for survival.

CONTEXTO E OBJETIVO: O carcinoma lobular é o segundo tipo de neoplasia mais frequente na mama e tem características clínicas e patológicas próprias. Nosso objetivo foi avaliar fatores prognósticos para esse tipo de câncer de mama. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo em instituição terciária oncológica. MÉTODOS: 162 pacientes diagnosticadas e tratadas entre janeiro de 1985 e janeiro de 2002 foram incluídas. Os critérios de inclusão foram: ausência de tratamento prévio, diagnóstico histológico de carcinoma lobular, ausência de história prévia de câncer de mama e acompanhamento mínimo de 36 meses. RESULTADOS: Em análise univariada, os seguintes fatores foram estatisticamente significativos: estágio T clínico (P = 0,0005), estágio N clínico (P = 0,0014), quimioterapia neoadjuvante (P = 0,0008), tamanho do tumor primário (P < 0,0001), invasão vascular (P < 0,0001), invasão linfática (P = 0.0004), invasão neural (P = 0,0004), invasão de pele (P < 0,0001), transposição capsular (P = 0,0008), relação linfonodal (P < 0,0001), expressão de receptor estrogênico (P = 0,0168), expressão de receptor de progesterona (P = 0,0286), estágio T patológico (P < 0,0001), estágio N patológico (P < 0,0001), quimioterapia adjuvante (P < 0,0001) e hormonioterapia pós-operatória (P = 0.0367). Agrupando-se as variáveis, realizou-se análise multivariada. Presença de metástases linfonodais, transposição capsular, razão linfonodal e hormonioterapia pós-operatória permaneceram significantes. CONCLUSÃO: Nesta série, os fatores prognósticos mais importantes para carcinoma lobular de mama parecem ser aqueles relacionados com status linfonodal e presença de transposição capsular. Fatores relacionados ao comprometimento axilar, transposição capsular e terapia hormonal foram significativos para sobrevida.

Validation, reliability and comprehension of the IBCSG quality of life questionnaire specific to breast cancer

OBJECTIVE: To evaluate overall survival in incident cases of oral cancer notified by the Goiânia population-based cancer registry between 1988 and 2002.PATIENTS AND METHODS: A total of 313 incident cases of squamous cell carcinoma of the oral cavity were identified. The variables studied were: age, gender and clinical staging. Data regarding vital status were obtained from the medical charts of the hospital and clinics and from the Goiânia Mortality Data System. RESULTS: Of the 313 incident cases of oral cancer notified between 1988 and 2002 that were identified in this study, 245 (72.7%) occurred in males and 92 (27.3%) in females. The five year overall survival rate for oral cancer in Goiânia was 35.3% with a mean survival time of 30 months (95%CI, 27-32). There was no statistically significant difference in survival time between males and females (35.8% versus 33.9%; p = 0.750). In patients with tumors < 4 cm, survival rate was 77%, whereas in patients with tumors > 4 cm, survival rate was 39% (µ = 35 months, 95%CI, 31-38, p < 0.001).CONCLUSION: In patients with oral cancer, survival is associated with gender, age at diagnosis and treatment of these tumors. The low survival rates found indicate that the majority of tumors were at an advanced stage. Training healthcare professionals to clinically examine the oral cavity, to identify abnormalities in oral mucosa and to duly refer patients to a specialized service for early diagnosis would lead to an improvement in survival

ADAM23 negatively modulates alpha(v)beta(3) integrin activation during metastasis.

The ADAM23 gene is frequently silenced in different types of tumors, and, in breast tumors, silencing is correlated with tumor progression, suggesting that it might be associated with the acquisition of a metastatic phenotype. ADAM23 exerts its function mainly through the disintegrin domain, because its metalloprotease domain is inactive. Analysis of ADAM23 binding to integrins has revealed a specific interaction with alpha(v)beta(3) integrin mediated by the disintegrin domain. Altered expression of alpha(v)beta(3) integrin has been observed in different types of tumors, and expression of this integrin in the activated form has been shown to promote metastasis formation. Here, we investigated the possibility that interaction between ADAM23 and alpha(v)beta(3) integrin might negatively modulate alpha(v)beta(3) activation during metastatic progression. ADAM23 expression was knocked down using short hairpin RNA in the MDA-MB-435 cell line, which has been extensively used as a model for alpha(v)beta(3) integrin activation. Ablation of ADAM23 enhanced alpha(v)beta(3) integrin activation by at least 2- to 4-fold and ADAM23 knockdown cells showed enhanced migration and adhesion to classic alpha(v)beta(3) integrin ligands. Ablation of ADAM23 expression also enhanced pulmonary tumor cell arrest in immunodeficient mice. To complement our findings with clinical evidence, we showed that silencing of ADAM23 gene by DNA promoter hypermethylation in a collection of 94 primary breast tumors was significantly associated with lower distant metastases-free and disease-specific survivals and was an independent prognostic factor for poor disease outcome. Our results strongly support a functional role of ADAM23 during metastatic progression by negatively modulating alpha(v)beta(3) integrin activation.

P53 expression is a factor for prognostic assessment in breast sarcoma.

The present study was undertaken with the aim of evaluating the clinical and anatomopathological findings, emphasizing expression of the protein p53 as possible prognostic markers, in patients with breast sarcoma. p53 immunohistochemical expression was determined in archival paraffin embedded tissue blocks of 30 breast sarcoma patients, (19 fibrosarcomas, nine malignant fibrohistiocytomas and two liposarcomas) treated at the Hospital do Cancer AC Camargo, São Paulo, Brazil from 1955 to 1990. Immunopositivity was present in 50% of the cases. The survival of the patients was compared with the above parameters. Median follow up time was 113 months. The 5 years specific survival rates were 55.1% for patients with a positive expression of p53 contrariwise to 92.3% of specific survival found in p53 negative patients (p = 0.04). Positive expression of p53 was found in 3/4 (75%) of the patients with local recurrence and in 7/9 (77%) of patients with metastatic disease. No significant correlation between survival and clinicopathologic features (age, menopausal status, tumor size, stage and histological type), was found. A slight positive correlation between high grade and poor outcome was observed, 89% of the metastatic cases being classified as high grade (p = 0.02, by one sided Fisher's exact test). When we have compared, independently, survival probability curves between p53 positive/negative expression and each category of clinicopathologic features a worse prognosis was observed when p53 was positive in patients older than 50 years (p = 0.01), in tumors larger than 5 cm (p = 0.02), within the malignant fibrous histiocytoma subtype (p = 0.01) and in tumors classified as high grade (p = 0.07). In conclusion p53 expression seems to be a useful prognostic marker for this type of tumor.

Cystosarcoma phyllodes variedade benigna (fibroadenoma intracanicular hipercelular): consideraçöes clínicas e anatomopatológicas / Benign cystosarcoma phyllodes (cellular fibroadenoma): a clinicopathological analysis

Foram analisados sete casos de hidropsia fetal nao imunitaria, do ponto de vista etiológico. Verificou-se a ocorrência de doenças infecciosas e anomalias congênitas na gênese do quadro. Todos os casos tiveram a etiologia determinada graças à propedêutica empregada.

Câncer de mama no homem / Cancer of the male breast

Foram analisados retrospectivamente 60 casos de câncer de mama no homem, atendidos no período compreendido entre maio de 1953 e abril de 1988. Eles correspondem a 0,6 por cento de todos od casos vistos no período, em ambos os sexos. A idade média foi de 52,6 anos, ou seja, cinco anos maior do que na mulher. O tempo médio de queixa mostrou-se bastante elevado: 37,7 meses. Essa demora na procura do médico, aliada à maior proximidade do tumor à pele e ao plano muscular, explica a pequena frequência de casos iniciais: apenas dois do estádio clínico I e nenhum caso do estádio II. O carcinoma ductal infiltrado ocorreu em 78,3 por cento dos casos. A mastectomia radical clássica foi a operaçäo de eleiçäo e nos pacientes assim operados há mais de cinco anos, a sobrevida total foi de 46,7 por cento sem nenhuma recidiva local. A radioterapia pós-operatória foi empregada em 12 casos. Considerando que 60 por cento pertenciam ao estádio III e 26,7 por cento já eram biopsiados anteriormente, esses resultados podem ser considerados equivalentes aos da mulher