TET2 Negatively Regulates Nestin Expression in Human Melanoma.

Although melanoma is an aggressive cancer, the understanding of the virulence-conferring pathways involved remains incomplete. We have demonstrated that loss of ten-eleven translocation methylcytosine dioxygenase (TET2)-mediated 5-hydroxymethylcytosine (5-hmC) is an epigenetic driver of melanoma growth and a biomarker of clinical virulence. We also have determined that the intermediate filament protein nestin correlates with tumorigenic and invasive melanoma growth. Here we examine the relationships between these two biomarkers. Immunohistochemistry staining of nestin and 5-hmC in 53 clinically annotated primary and metastatic patient melanomas revealed a significant negative correlation. Restoration of 5-hmC, as assessed in a human melanoma cell line by introducing full-length TET2 and TET2-mutated constructs, decreased nestin gene and protein expression in vitro. Genome-wide mapping using hydroxymethylated DNA immunoprecipitation sequencing disclosed significantly less 5-hmC binding in the 3' untranslated region of the nestin gene in melanoma compared to nevi, and 5-hmC binding in this region was significantly increased after TET2 overexpression in human melanoma cells in vitro. Our findings provide evidence suggesting that nestin regulation is negatively controlled epigenetically by TET2 via 5-hmC binding at the 3' untranslated region of the nestin gene, providing one potential pathway for understanding melanoma growth characteristics. Studies are now indicated to further define the interplay between 5-hmC, nestin expression, and melanoma virulence.

Fragment c gamma receptor gene polymorphisms and breast cancer risk in case-control studies in Japanese, Japanese Brazilians, and non-Japanese Brazilians.

Previous studies showing the presence of antibodies against tumor-associated antigens in healthy individuals suggest that antibody-dependent cell cytotoxicity (ADCC) might play a role in the development of breast cancer. We hypothesized that functional polymorphisms in fragment c gamma receptor (FcgR) genes were associated with breast cancer risk. We conducted hospital-based case-control studies of patients aged 20-74 years with invasive breast cancer, and matched controls from medical checkup examinees in Nagano, Japan and from cancer-free patients in São Paulo, Brazil. A total of 869 pairs (403 Japanese, 80 Japanese Brazilians and 386 non-Japanese Brazilians) were genotyped for two single nucleotide polymorphisms (SNPs): a histidine (H)/arginine (R) polymorphism at position 131 of FcgRIIa (FcgRIIa H131R) and a valine (V)/phenylalanine (F) polymorphism at position 158 of FcgRIIIa (FcgRIIIa F158V). We found no statistically significant association between either of the two SNPs and breast cancer risk regardless of population. In analyses of the three populations combined, adjusted odds ratio (OR) was 0.93 [95% confidence interval (CI) 0.66-1.32] for women with the R/R versus H/H genotype of the FcgRIIa H131R polymorphism and 1.04 (95% CI 0.69-1.57) for the V/V versus F/F genotype of the FcgRIIIa F158V polymorphism. On combination of the two SNPs, compared to women with both the R/R genotype of the FcgRIIa H131R polymorphism and F/F genotype of the FcgRIIIa F158V polymorphism, the adjusted OR for women with both the H/H and V/V genotype was 0.68 (95% CI 0.37-1.27). In conclusion, our findings suggest that ADCC might not play a major role in the etiology of breast cancer.

Analysis of prognostic factors in patients with oropharyngeal squamous cell carcinoma treated with radiotherapy alone or in combination with systemic chemotherapy.

OBJECTIVE: To assess the prognostic significance of several factors in oropharyngeal squamous cell carcinoma treated with radiotherapy alone or in combination with chemotherapy. DESIGN: Retrospective study. SETTING: Erasto Gaertner Hospital, Curitiba, Brazil, and A. C. Camargo Hospital, São Paulo, Brazil. PATIENTS: A total of 361 patients treated for squamous cell carcinoma from January 1, 1990, to December 31, 2001. INTERVENTIONS: Radiotherapy alone or with chemotherapy. MAIN OUTCOME MEASURES: Disease-free survival, overall survival, and treatment response. RESULTS: Most tumors were located at the tonsil (46.8%) or base of the tongue (28.0%) and were at clinical stage III or IV (92.8%). Treatment response was associated with Zubrod scale score, weight loss, number of comorbidities, symptom-severity and Piccirillo stages, hemoglobin level, tumor site, macroscopic appearance of the tumor, and clinical stage. The 5-year overall survival rate was 17.6% and disease-free survival rate was 16.2%. The significant prognostic variables were age; Zubrod scale score; weight loss; comorbidities; Berg, Piccirillo, and symptom-severity staging; involvement of adjacent soft-tissue areas and bone; lymph node mobility; clinical stage; and radiotherapy doses. The multivariate analysis showed Zubrod scale score, symptom-severity staging system, Berg staging system, comorbidities, and radiotherapy dose as independent prognostic factors. CONCLUSION: A combination of clinical factors, such as symptoms, patients' general status, weight loss, and comorbidities, leads to a relevant stage of clinical severity that can be associated with the TNM stage as predictors of survival in oropharyngeal carcinoma.

Dental extractions related to head and neck radiotherapy: ten-year experience of a single institution.

OBJECTIVE: This study evaluates the frequency of osteoradionecrosis associated with dental extractions. STUDY DESIGN: A total of 405 patients submitted to radiotherapy and had dental extractions were evaluated. The patients were divided into 3 groups. RESULTS: In group 1, 316 patients were submitted to 1.647 dental extractions (mean 5.2 teeth per patient) and in another 47 patients the number of teeth removed was not clearly reported. Group 2 comprised 5 patients who had 33 teeth extracted (mean 6.6 each). In group 3, 55 patients had 290 teeth removed (mean 5.3 each) and in another 2 patients the number of dental extractions could not be established. In general, only 3 cases of osteoradionecrosis related to dental extractions were observed: 2 related to exodontias performed before and 1 after radiotherapy. CONCLUSIONS: The low prevalence of osteoradionecrosis found in this work suggests the possibility of performing exodontias after radiotherapy by experienced dentists in the management of head and neck cancer.

Quality of life related to swallowing after tongue cancer treatment.

The surgical treatment of tongue cancer, with or without reconstruction and/or radiotherapy, leads to different levels of voice, speech, and deglutition disorders. Evaluating the quality of life related to these swallowing alterations is important to further our knowledge about the impact of such alterations from the patient's point of view. Our objective was to describe the quality of life related to swallowing in patients treated for tongue cancer, using specific questionnaires. Twenty-nine patients participated in the study for a minimum of one year after oncologic treatment. Patients with advanced disease who underwent radiotherapy had significantly worse scores in most domains. The aspects related to how to deal with deglutition problems, time taken for meal consumption, pleasure in eating, chewing problems, food sticking in throat and mouth, choking, and the knowledge of feeding restrictions, which were evaluated by different domains of SWAL-QOL, were factors that contributed to a negative impact for patients with advanced-stage tumors who underwent radiotherapy.

ErbB2 and fatty acid synthase (FAS) expression in 102 squamous cell carcinomas of the tongue: correlation with clinical outcomes.

The oncoprotein ErbB2 (HER-2/neu) is a tyrosine kinase cell surface receptor overexpressed in several human malignancies, including oral squamous cell carcinoma (OSCC). ErbB2 was recently shown to regulate the expression of fatty acid synthase (FAS), a multifunctional enzyme complex responsible for the de novo biosynthesis of saturated fatty acids. Here we evaluated the relationship between the immunohistochemical expression of ErbB2, FAS, and Ki-67 with the clinicopathologic characteristics of tongue squamous cell carcinoma (SCC). One hundred and two patients with tongue SCC treated from 1990 to 1995 were studied. Clinical and treatment data were obtained from the medical records and histopathological features revised. Paraffin-embedded tissues were submitted to standard immunohistochemical reactions for ErbB2, FAS and Ki-67. A strong positive correlation between ErbB2 labeling at the cell membrane and FAS expression was found in the tongue SCC samples (p<0.0001). The intracytoplasmatic expression of ErbB2 as well as Ki-67 nuclear staining were significantly associated with a high risk of recurrence by predicting both disease free survival (log-rank test, p=0.0096 and p=0.0047, respectively) and overall survival (log-rank test, p=0.0029 and p=0.0001, respectively). Taken together, our results suggest that the immunolocalization of ErbB2 at the cell surface of malignant oral keratinocytes is linked to FAS expression whereas the intracytoplasmatic ErbB2 or Ki-67 staining predict high risk of recurrence of tongue SCC.

C-erbB-2 expression is a better predictor for survival than galectin-3 or p53 in early-stage breast cancer.

The definition of high risk patients with early stage breast cancer is still controversial. We evaluated the ability of galectin-3, c-erbB-2 and p53 immunohistochemical expression to predict recurrence and survival in a homogeneous set of 92 patients with T1N0M0 ductal carcinoma with a long-term follow-up. In normal breast tissue, the epithelial and fibroblast components were positive for galectin-3 mostly showing nuclear and cytoplasmic reactivity. At the tumor epithelial component, galectin-3 expression was found in 46.7% of the samples with a predominant cytoplasmic staining. Similar results were presented by concurrent in situ lesions. Tumor stromal fibroblasts maintained positivity in 70 out of 92 cases (76%). We found expression of p53 in only 16 cases (17.4%), and c-erbB-2 in 17 (18.48%). A marginal association was found between co-expression of p53 and galectin-3 (p=0.055) and a significant correlation between p53 accumulation and c-erbB-2 expression (p=0.009). There was no significant association between galectin-3 protein expression with disease-free survival or overall survival. C-erbB2 and p53 expression correlated with recurrence (p=0.002, p=0.02; respectively). Diminished overall survival at 10 years was associated with c-erbB-2 (p=0.010), but marginally with p53 expression (p=0.076). Epithelial galectin-3 expression cannot be considered a prognostic factor for patients with T1N0M0 breast cancer, p53 seems to be of minor relevance and c-erbB-2 expression was the best discriminator and may be a marker for aggressive clinical behavior in patients with early stage breast cancer.

Expression of PCNA, p53, Bax, and Bcl-X in oral poorly differentiated and basaloid squamous cell carcinoma: relationships with prognosis.

BACKGROUND: The aim of this study was to compare the clinical features and proliferating cell nuclear antigen (PCNA), p53, Bcl-X, and Bax expression in primary oral basaloid squamous cell carcinoma (BSCC) and poorly differentiated squamous cell carcinoma (PDSCC) matched by stage and site and to assess the possible prognostic significance of these variables. METHODS: Seventeen cases of oral BSCC were compared with 27 PDSCCs matched by stage and tumor site. In addition, PCNA, p53, Bax, and Bcl-X expression in both carcinomas were evaluated in relation to their clinicopathologic features and prognostic values using the Kaplan-Meier method and Cox regression models. RESULTS: No statistically significant differences were found between the groups (BSCC and PDSCC) in regard to clinical features and immunohistochemical reactivity for antibodies PCNA, p53, and Bcl-X. In comparison with PDSCC, the BSCC group exhibited a higher Bax score (p = .031). The 5-year and 10-year overall survival, cancer-specific survival, and disease-free survival rates demonstrated no significant differences between the BSCC and PDSCC groups, and the PCNA, p53, Bax, and Bcl-X also showed no prognostic value. CONCLUSIONS: These results suggest that the clinical and biologic course of BSCC is similar to PDSCC in the oral cavity when clinical stage and site are matched.

DNA methylation in the CTCF-binding site I and the expression pattern of the H19 gene: does positive expression predict poor prognosis in early stage head and neck carcinomas?

Loss of allele-specific expression by the imprinted genes IGF2 and H19 has been correlated with a differentially methylated region (DMR) upstream to the H19 gene. The H19-DMR contains seven potential CCCTC-binding factor (CTCF) binding sites. CTCF is a chromatin insulator and a multifunctional transcription factor whose binding to the H19-DMR is suppressed by DNA methylation. Our study included a group of 41 head and neck squamous cell carcinoma (HNSCC) samples. The imprinting status of the H19 gene was analyzed in 11 out of 35 positive cases for H19 gene expression, and only 1 of them showed loss of imprinting. We detected a significant correlation (P = 0.041, Fisher's exact test) between H19 expression and tumor recurrence. Among H19 positive cases, six were T2, in which five developed recurrence and/or metastasis. Inversely, in the group of tumors that showed no H19 gene expression, 5 out of 24 were T2 and only 1 presented regional recurrence. These data support the hypothesis that H19 expression could be used as a prognostic marker to indicate recurrence in early stage tumors. We also examined the methylation of the CTCF binding site 1 in a subgroup of these samples. The H19 gene silencing and loss of imprinting were not correlated with the methylation pattern of the CTCF binding site 1. However, the significant correlation between H19 expression and tumor recurrence suggest that this transcript could be a marker for the progression of HNSCC.

Quality of life and depression in patients undergoing total and partial laryngectomy.

PURPOSE: The surgical treatment of head and neck cancer, primarily laryngeal cancer, causes sequelae and can change the patient's quality of life. The purpose of this study was to investigate the impact of laryngectomy on the quality of life regarding the functional, physical, psychological, and social aspects. METHODS: Fourteen patients underwent total laryngectomy and 16 underwent vertical partial laryngectomy. The Quality of Life Core Questionnaire (QLQ-C30) and Head and Neck (H&N35) questionnaire from the European Organization for Research and Treatment of Cancer (EORTC) were used for quality of life evaluation, while the Beck Depression Inventory questionnaire was used for the depression screen. RESULTS: In the total laryngectomy group, reported adverse effects were worsened, social and emotional function (21.3%), olfaction and taste changes (85.6%), cough (71.3%), speech difficulty (100%), and dysphagia (64.3%). Most of the patients (85.5%) judged their quality of life to be reasonable. In the partial laryngectomy group, reported adverse effects were worsened, emotional function (71.4%), speech difficulty (100%), and dysphagia (31.3%). However, most of the patients judged their quality of life to be above the general average. CONCLUSION: Despite being different surgeries, both groups experienced similar difficulties but at different levels. The quality of life was judged worse in the patients who underwent total laryngectomy.

Quality of life and depression in patients undergoing total and partial laryngectomy

OBJETIVO: O tratamento cirúrgico para o câncer de cabeça e pescoço, especificamente para o câncer de laringe, deixa seqüelas nos pacientes podendo alterar sua qualidade de vida. O objetivo deste estudo foi pesquisar o impacto na qualidade de vida, no que diz respeito aos aspectos funcionais, físicos, psicológicos, sociais e o rastreamento da depressão. MÉTODO: Foram estudados 14 pacientes submetidos a laringectomia total e 16 pacientes submetidos a laringectomia parcial vertical. Para a avaliação da qualidade de vida utilizamos os questionários da Organização Européia de Pesquisa e Tratamento do Câncer (EORTC), Quality of Life Core Questionnarie (QLQ-C30) e Head and Neck 35 (H&N35) e, para o rastreamento da depressão, o questionário Beck Depression. RESULTADOS: As funções social e emocional foram as mais afetadas no grupo de laringectomia total. 21,3% dos pacientes julgaram mediana sua qualidade de vida global. Dentro dos sintomas específicos, 85,5% referiram alteração no olfato e paladar, 71,3% tosse, 100% algum grau de dificuldade na fala e 64,3% dificuldades com a deglutição. No grupo de laringectomia parcial encontramos a função emocional afetada em 71,4%, a maioria julgou sua qualidade de vida global acima da média, 100% demonstraram algum grau de dificuldade com a fala e 31,3% referiram disfagia. CONCLUSAO: Embora sendo cirurgias diferentes, ambos os grupos passaram por dificuldades similares em maior ou menor grau. Os resultados demonstraram piora nos parâmetros de qualidade de vida dos pacientes submetidos a laringectomia total.

Looking Beyond Tobacco and Alcohol: The Role of Lifestyle and Other Environmental Risk Factors for Laryngeal Cancer

Laryngeal cancer incidence in São Paulo, Brazil, is one of the highest in the world. OBJECTIVE: This hospitalbasedcase-control study was designed to investigate exposure-disease relationship between larynx cancer andsmoking and drinking history, diet, occupational exposures and other characteristics. MATERIAL ANDMETHODS: The study was conducted in 3 metropolitan areas in Brazil: São Paulo (South-east), Curitiba (South)and Goiânia (Central-west). We have analyzed information on demographics, occupational history, environmental exposures, tobacco smoking and alcoholdrinking habits obtained from interviews with 194 cases and 804 controls (non-cancer inpatients) matched on 5-year age group, gender, hospital catchments area, and trimester of admission. RESULTS: Tobacco and alcohol consumption were the most important factors for prediction of laryngeal cancer. Other important riskfactors were indoor exposure to wood stove fumes (RR=2.6), woodworking (RR=1.9), family history of cancer(RR=2.1), and high consumption of coffee and “chimarrão”(a kind of maté tea ). There was a protective effect for the consumption of citric fruits and forcarotene-rich vegetables. CONCLUSION: regionally specific lifestyle (“chimarrão”, high consumption of woodworking, and family history of cancer may be responsible for a substantial proportion of incidentlaryngeal cancer cases.

Valor prognóstico de p53 e PCNA em carcinomas espinocelulares da cavidade oral / Prognostic value of p53 and PCNA in squamous cell carcinoma of oral cavity

Embora o carcinoma espinocelular (CEC) seja a neoplasia mais comum da cavidade oral, os fatores prognósticos deste tumor ainda não são completamente conhecidos. O objetivo do presente estudo foi analisar o padrão de expressão de PNCA e p53 e suas influências na sobrevida de pacientes em CECs da cavidade oral. Cinqüenta e uma amostras de CECs foram analisadas por imuno-histoquímica utilizando-se anticorpos monoclonais contra as proteínas PCNA e p53, e a porcentagem de expressão nuclear foi determinada e correlacionada com as informações clínicas dos pacientes. Todas as amostras foram positivas para PCNA, com uma média de células positivas de 66+/-16,3%, enquanto que 36 das 51 amostras (70,6%) foram positivas para a proteína p53, com uma média de 31.1+/-27,7%. Pacientes com neoplasias com metástases regionais ou com tumores primários grandes (T3 e T4) apresentaram índices de expressão para PCNA significantemente maiores que neoplasias menores ou sem metástases regionais (p<0,05). A expressão de p53 não foi correlacionada com nenhum dos parâmetros analisados. Os resultados do presente estudo demonstraram que a detecção imuno-histoquímica de p53 não apresenta um valor prognóstico para pacientes com CECs orais, enquanto que a expressão de PCNA correlaciona com o tamanho do tumor primário e a presença de metástases regionais

Clinical significance of c-myc and p53 expression in head and neck squamous cell carcinomas.

c-myc and p53 genes were frequently deregulated in head and neck squamous cell carcinoma (HNSCC). To determine if the concomitant expression of the two oncogenes might have prognostic value, the survival and free disease time of 140 consecutive HNSCC patients followed up for a median time of 29.9 months was analyzed in the light of p53 and c-myc expression assessed by immunohistochemistry. Positive c-myc and p53 staining was detected respectively in 35.7 and 50.7% of the tumors. Double positivity emerged in 16.4% of the cases. Overall-survival of patients was not associated with the immunoreactivity of p53 or c-myc considered separately or grouped in subsets. Considering only the advanced stages, the concomitant expression of both oncogenes in tumors was associated with worse disease-free survival (P = 0.004) suggesting a role for p53 and c-myc genes in progression of this HNSCC subset. Clinical parameters (presence of lymph nodes, histologic grade and tumor width) remained important indicators of overall survival (OS).

Expression of fatty acid synthase, ErbB2 and Ki-67 in head and neck squamous cell carcinoma. A clinicopathological study.

Fatty acid synthase (FAS) is a multifunctional enzyme responsible for the synthesis of saturated fatty acids using acetyl-CoA and malonyl-CoA as substrates. Overexpression of FAS has been reported in several human malignancies and suggested as a potential prognostic factor. ErbB2 (Her-2/neu), a transmembrane tyrosine kinase member of the ErbB receptor family, is known to be overexpressed in a variety of tumors and was recently shown to regulate FAS production in breast epithelial cell lines. Herein we analyzed by immunohistochemistry the expression of FAS, ErbB2, and the proliferation marker Ki-67 in 62 head and neck squamous cell carcinoma (HNSCC) samples. Approximately 78% of the cases were positive for FAS or ErbB2 at the cell membrane and 70% of the tumors that showed a high expression of FAS were also strongly positive for ErbB2 (Fisher's exact test, p = 0.01). The immunolabeling for both FAS and ErbB2 was stronger in histologically well-differentiated lesions. Additionally, Ki-67 expression was significantly associated with a poor prognosis (log-rank test, p = 0.03). Taken together, the results presented here suggest that ErbB2 regulates FAS expression in HNSCC and point out Ki-67 as a useful prognostic marker for these tumors.

Androgen receptor CAG repeat polymorphism in prostate cancer from a Brazilian population.

Shorter CAG repeats in the androgen receptor (AR) gene have been associated with increased prostate cancer risk. Aiming to investigate whether the AR CAG polymorphism is associated with an increased relative risk for prostate cancer in our population, genomic DNA from 133 prostate cancer patients and 279 healthy men controls were examined. We found no association between the AR CAG polymorphism and the relative risk of prostate cancer in white Brazilian individuals with a CAG repeat length

Transforming growth factor beta1 (TGFbeta1) expression in head and neck squamous cell carcinoma patients as related to prognosis.

BACKGROUND: Transforming growth factor beta1 (TGFbeta1) is a negative growth regulator in keratinocytes, and in vitro studies lead to the concept that loss of TGFbeta1 responsiveness is a critical step in epithelial carcinogenesis. OBJECTIVE: To investigate the prognostic relevance of TGFbeta1 expression in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: TGFbeta1 distribution was determined by immunohistochemistry in oral cavity/oropharynx (n = 79), larynx (n = 36) and hypopharynx (n = 25) tumors and in matched normal adjacent mucosa. TGFbeta-type I and II receptors were determined in 20 cases of differentiated oral cavity/hypopharynx tumors. Cases were considered positive if displaying reactivity in >10% of the cells. RESULTS: TGFbeta1-positive expression was found in 47.2% of larynx, 36.7% of oral cavity/oropharynx and in 24% of the hypopharynx tumors. Reactivity in >60% of the cells was displayed only by 11.4% of HNSCC. All normal controls were positive. TGFbeta1-positive expression did not correlate with clinico pathological parameters. An association with differentiation was verified only in oral cavity/oropharynx tumors (P

Quantitative real-time PCR identifies a critical region of deletion on 22q13 related to prognosis in oral cancer.

Quantitative real time PCR was performed on genomic DNA from 40 primary oral carcinomas and the normal adjacent tissues. The target genes ECGFB, DIA1, BIK, and PDGFB and the microsatellite markers D22S274 and D22S277, mapped on 22q13, were selected according to our previous loss of heterozygosity findings in head and neck tumors. Quantitative PCR relies on the comparison of the amount of product generated from a target gene and that generated from a disomic reference gene (GAPDH-housekeeping gene). Reactions have been performed with normal control in triplicates, using the 7700 Sequence Detection System (PE Applied Biosystems). Losses in the sequences D22S274 (22q13.31) and in the DIA1 (22q13.2-13.31) gene were detected in 10 out of 40 cases (25%) each. Statistically significant correlations were observed for patients with relative copy number loss of the marker D22S274 and stages T3-T4 of disease (P=0.025), family history of cancer (P=0.001), and death (P=0.021). Relative copy number loss involving the DIA1 gene was correlated to family history of cancer (P<0.001), death (P=0.002), and consumption of alcohol (P=0.026). Log-rank test revealed a significant decrease in survival (P=0.0018) for patients with DIA1 gene loss. Relative copy number losses detected in these sequences may be related to disease progression and a worse prognosis in patients with oral cancer.

Chemoradiation instead of surgery to treat mid and low rectal tumors: is it safe?

BACKGROUND: The main treatment for rectal carcinoma is surgery. Preoperative chemoradiation (CRT) is advocated to reduce local recurrence and improve resection of mid and low tethered rectal tumors. METHODS: Fifty-two patients with mid or low rectal tumors underwent CRT (external beam radiation plus 5-fluorouracil plus folinic acid). Patients who had low rectal tumors with complete response (CR) were not submitted to surgical treatment. All other patients were submitted to surgery, independently of the response. Mean follow-up was 32.1 months. RESULTS: Five-year overall survival was 60.5%. Clinical evaluation after CRT showed CR in 10 cases (19.2%), all low tumors; incomplete response (>50%) in 21 (40.4%); and no response (<50%) in 19 (36.6%). Among the 10 cases with CR, 8 presented with local recurrence within 3.7 to 8.8 months. Two patients were not submitted to surgery and are still alive without cancer after 37 and 58 months. Thirty-nine patients had radical surgery. Seven had local recurrences after CRT plus surgery (17.9%). Overall survival was negatively affected by lymph node metastases (P =.017) and perineural invasion (P =.026). CONCLUSIONS: Exclusive CRT approach is not safe to treat patients with low infiltrative rectal carcinoma.

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.