Role of magnetic resonance imaging in the prediction of histological grade in soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas are rare malignant tumors with significant heterogeneity. The importance of classifying histological grades is fundamental to defining the treatment approach. OBJECTIVE: To evaluate magnetic resonance imaging (MRI) in predicting the histological grade of soft tissue sarcomas. METHODS: A retrospective observational study included patients over 18 years undergoing MRI and primary tumor surgery at AC Camargo Cancer Center from January 2015 to June 2022. Two radiologists evaluated MRI criteria (size, margin definition, heterogeneity of the T2 signal, high-intensity peritumoral signal on T2, and postperitumoral contrast), and a grading prediction score was calculated. χ2 and logistic regression analyses were conducted. RESULTS: Sixty-eight patients were included (38 men; median: 48 years). Moreover, 52 high-grade and 16 low-grade tumors were observed. The MRI criteria associated with histological grade were peritumoral high-intensity T2-weighted signals (p < 0.001) and peritumoral postcontrast enhancement (p = 0.006). Logistic regression confirmed their significance (odds ratio [OR]: 11.8 and 8.8, respectively). Each score point increment doubled the chance of high-grade tumors (OR: 2.0; p = 0.014). CONCLUSION: MRI effectively predicts histological grades of soft tissue sarcomas. Peritumoral high-intensity T2-weighted signals and peritumoral postcontrast enhancement are valuable indicators of high-grade tumors. This highlights MRI's importance in treatment decision-making for sarcoma patients.

COLORECTAL CANCER: ASSOCIATION BETWEEN SOCIODEMOGRAPHIC VARIABLES AND THE ADHERENCE TO CANCER SCREENING.

BACKGROUND: Colorectal cancer (CRC) is a worldwide health problem whose control depends on public policy establishment and effective prevention and screening programs. In Brazil, there are few studies related to adherence to screening methods. AIMS: The aim of this study was to evaluate the association between demographic and socioeconomic to adherence to CRC screening with fecal immunochemical test (FIT) among average-risk individuals for CRC. METHODS: In this prospective cross-sectional study, conducted between March 2015 and April 2016, 1,254 asymptomatic individuals aged 50-75 years, participating in a hospital screening campaign in Brazil, were invited to participate in the study. RESULTS: The adherence rate to FIT was 55.6% (697/1,254). In the multivariable logistic regression analysis, patients aged 60-75 years (odds ratio (OR)=1.30; 95% confidence interval (CI): 1.02-1.66; p=0.03), religious belief (OR=2.04; 95% CI: 1.34-3.11; p<0.01), previous fecal occult blood test (OR=2.07; 95% CI: 1.55-2.76; p<0.01), and full/part-time working status (OR=0.66; 95% CI: 0.49-0.89; p<0.01) were independently associated with adherence to CRC screening. CONCLUSION: The results of the present study highlight the importance of considering the labor aspects when implementing screening programs, suggesting that campaigns conducted in the workplace and repeated over the years may be more effective.

Câncer colorretal: associação entre variáveis sociodemográficas e a adesão a programas de rastreamento / Colorectal cancer: association between sociodemographic variables and the adherence to cancer screening

ABSTRACT BACKGROUND Colorectal cancer (CRC) is a worldwide health problem whose control depends on public policy establishment and effective prevention and screening programs. In Brazil, there are few studies related to adherence to screening methods. AIMS: The aim of this study was to evaluate the association between demographic and socioeconomic to adherence to CRC screening with fecal immunochemical test (FIT) among average-risk individuals for CRC. METHODS: In this prospective cross-sectional study, conducted between March 2015 and April 2016, 1,254 asymptomatic individuals aged 50-75 years, participating in a hospital screening campaign in Brazil, were invited to participate in the study. RESULTS: The adherence rate to FIT was 55.6% (697/1,254). In the multivariable logistic regression analysis, patients aged 60-75 years (odds ratio (OR)=1.30; 95% confidence interval (CI): 1.02-1.66; p=0.03), religious belief (OR=2.04; 95% CI: 1.34-3.11; p<0.01), previous fecal occult blood test (OR=2.07; 95% CI: 1.55-2.76; p<0.01), and full/part-time working status (OR=0.66; 95% CI: 0.49-0.89; p<0.01) were independently associated with adherence to CRC screening. CONCLUSION: The results of the present study highlight the importance of considering the labor aspects when implementing screening programs, suggesting that campaigns conducted in the workplace and repeated over the years may be more effective.

RESUMO RACIONAL: O câncer colorretal (CCR) é um problema de saúde mundial cujo controle depende do estabelecimento de políticas públicas e programas de prevenção e rastreamento eficazes. No Brasil existem poucos estudos relacionados à adesão métodos de rastreamento. OBJETIVO: Avaliar a associação de características sócio-demográficas à realização de testes de sangue oculto nas fezes do tipo imunoquimicomecanizado (FIM) em população de médio risco para o desenvolvimento de câncer colorretal. MÉTODOS: Estudo observacional transversal, com coleta prospectiva de dados. Entre março de 2015 e abril de 2016, 1.254 indivíduos assintomáticos, com idade entre 50 e 75 anos, foram consecutivamente selecionados a partir de uma campanha hospitalar de rastreamento para neoplasias. RESULTADOS: As taxas de adesão ao teste FIM foi 55.6% (697/1254). Na análise de regressão logística múltipla os fatores independentes associados à adesão ao rastreamento do CCR foram: Idade entre 60-75 anos (oddsratio (OR)=1.30; intervalo de confiança de 95% (IC): 1.02-1.66; p=0.03), crença religiosa (OR=2.04; 95%IC: 1.34-3.11; p<0.01), realização prévia de exame de sangue oculto nas fezes (OR=2.07; 95%IC: 1.55-2.76; p<0.01) e vínculo empregatício em período integral ou parcial (OR=0.66; 95%IC: 0.49-0.89; p<0.01). CONCLUSÃO: Este estudo enfatiza a importância de considerar aspectos laborais ao implementar programas de rastreamento do câncer colorretal e sugere que campanhas de rastreamento implantadas no ambiente de trabalho e de maneira repetida ao longo dos anos podem ser mais efetivas.

Risk Factors for Development of Rectal Neuroendocrine Tumors Longer Than 9 mm: Retrospective Cohort.

BACKGROUND: Rectal neuroendocrine tumors (R-NET) represent the most frequent of gastroenteropancreatic neuroendocrine neoplasms (NEN-GEP) according to the United States Surveillance, Epidemiology, and End Results database. With an annual percentage of occurrence increasing to 8.2% of all rectal neoplasms, R-NET affect less than 2% and are reported in only 0.05% to 0.07% of patients undergoing colorectal cancer (CRC) screening. The primary objective of this study was to assess the risk factors associated with R-NET greater than 10 mm. As a secondary objective, it was also aimed to evaluate the response to endoscopic treatment. METHODS: This was a retrospective study, using data collected through the analysis of medical records of colonoscopies performed from January 2008 to December 2014. Records of polypectomies were identified, and the results were searched for pathological findings of R-NET. We also gathered epidemiological data and outcomes as risk factors for lesions greater than or equal to 10 mm, with local and distant recurrence. RESULTS: During the study period, 18 218 colonoscopies were performed and 10 865 polypoid lesions were detected and removed, 20 with R-NET anatomopathology. The detection rate was 0.1%. The risk factors associated with major lesions were Japanese ethnicity, the lack of previous cancer diagnosis, and a Ki67 index > 2%. The mean follow-up was 56.6 months, and there was no local lymph node recurrence or distant relapse. CONCLUSION: This study concludes that endoscopic resection is a good and effective method for treatment of Grade 1 rectal NET smaller than 11 mm, with high cure rates and low rates of local or distant relapse.

Late assessment of quality of life in patients with rectal carcinoma: comparison between sphincter preservation and definitive colostomy.

PURPOSE: Patients with cancer of the lower and middle rectum who are candidates for curative surgery often have negative opinions on definitive colostomy. The purpose of this study is to compare the quality of life (QoL) of patients who undergo standard treatment for rectal cancer with sphincter preservation or definitive colostomy. METHODS: A total of 125 patients with adenocarcinoma of the lower or middle rectum who underwent radical surgery with curative intent with a follow-up ≥ 1 year were recruited: 83 patients (group 1) were subjected to low anterior resection and low colorectal or coloanal anastomosis-thus preserving their sphincter-and 42 (group 2) were treated with abdominoperineal resection, followed by terminal definitive colostomy. QoL was assessed with the EORTC QLQ-C30 and QLQ-CR29 questionnaires. RESULTS: Health and global quality of life were similar between groups; however, patients who underwent definitive colostomy had higher scores on the emotional (p value = 0.016) and cognitive function scales (p value = 0.017). Patients with sphincter preservation presented with more symptoms that were related to stool frequency (p value < 0.001), intestinal constipation (p value = 0.005), fecal incontinence (p value = 0.001), buttock pain (p value = 0.023), and nausea and vomiting (p value = 0.036), whereas patients with permanent colostomy had higher scores for dysuria (p value = 0.033). CONCLUSION: Although global QoL scores did not differ between groups, patients who underwent definitive colostomy had significantly better functional and symptom scale scores, reflecting greater function with fewer symptoms.

Comparison between an immunochemical fecal occult blood test and a Guaiac based fecal occult blood test in detection of adenomas and colorectal cancer

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Brazil does not have an official well established program for screening colorectal cancer. The aim of this study was to compare Guaiac Based Fecal Occult Blood Test (G-FOBT) to a kind of an Immunochemical Fecal Occult Blood Test (I-FOBT), in search of cancer or advanced adenoma. Methods: Prospective and cross-sectional study. Asymptomatic and average-risk individuals (n = 1500) aged from 50 to 75 years old were invited to participate in the study. The primary endpoint was positivity rate and the secondary endpoints were adherence rate and significant endoscopic findings. All participants received both tests with follow-up colonoscopy if either test was positive. Results: Adherence rate of G- FOBT was 756/1500 (50.4%) while for I- FOBT it was 960/1500(64%). The positivity ratio in the I- FOBT was 94/960 (9.8%) and in the G-FOBT was 20/771 (2.6%). The Positive Predict Value (PPV) for the I- FOBT counted 16/77 (21.0%) while for the G- FOBT it was 6/18 (33.0%), considering significant lesions. Regarding the colorectal cancer findings, the detection in the colonoscopy guided from the positivity of fecal occult blood tests was 5/77 (6.5%) in I- FOBT and 2/18 (11.1%) on the G- FOBT. Conclusions: The positivity, the adherence rate and the capacity to detect significant lesions were higher in I-FOBT. Considering the findings of the study we could conclude that I-FOBT was superior to G- FOBT. Trial registration: This study was reviewed and approved by the Institutional Review Board of A.C.Camargo Cancer Center, São Paulo, Brazil, number: 1877/14

Estrogen Receptor ß as a Prognostic Marker of Tumor Progression in Colorectal Cancer with Familial Adenomatous Polyposis and Sporadic Polyps.

The incidence of colorectal cancer (CRC) is lower in women than in men, and sex steroids can be considered contributing factors because oral contraception usage and estrogen replacement therapy are associated with decreased risk. Conversely, colorectal polyp development in familial adenomatous polyposis (FAP) begins during puberty. The objectives were to evaluate the relationship between the expression of these hormone receptors and adenoma-carcinoma progression, CRC stage and overall survival. We studied 120 A.C. Camargo Cancer Center patients diagnosed with either FAP-associated or spontaneous adenomatous polyps or CRC to determine the immunohistochemical expression levels of estrogen receptor (ER)-α, ER-ß and the progesterone and androgen receptors (480 analyses). The ER-ß expression levels differed between the groups: the group with FAP polyps had lower ER-ß expression than that of the sporadic polyp group. With transformation of the sporadic polyps to cancer, there was a considerable decrease in ER-ß expression (from 90% with strong expression to 80% with absent or weak expression) (p < 0.001). The ER-ß expression was lower in T3/T4 tumors than in T1/T2 tumors (p = 0.015). The 5-year overall survival of CRC patients positively expressing ER-ß exceeded that of patients without detectable expression levels (74.8% vs. 44.3%, respectively; p = 0.035). There was no significant expression of the androgen or progesterone receptor or ER-α among the groups. Differences in ER-ß expression represent a potential mechanism through which estrogen might alter the susceptibility to colon cancer, thereby confirming the possibility of a protective role of estrogen against colorectal carcinogenesis.

Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer.

BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-ß (ERß). The expression of ERß isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described. METHODS: This study aimed to investigate the expression levels of the ERß1, ERß2, ERß4 and ERß5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas. RESULTS: Decreased expression of ERß isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p < 0.001). In FAP patients, ERß1 and ERß5 isoforms showed significant down-expression in polyps (p < 0.001) compared with matched normal tissues. However, no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERß isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERß was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p < 0.05). In sporadic colorectal cancer, the loss of expression was an independent predictor of recurrence, and ERß1 and ERß5 expression levels were associated with better disease-free survival (p = 0.002). CONCLUSION: These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.

Prognostic value of factors associated with hypoxia and lipid metabolism in patients with colorectal cancer

Background: Colorectal cancer (CRC) is a neoplasia with high incidence and mortality rates. It had been suggested that the inflammatory response is an important CRC prognostic factor. The disordered and accelerated proliferation of neoplastic cells decreases the oxygen and nutrient supply, generating a microenvironment characterized by hypoxia, necrosis and inflammation. This study aimed to evaluate the impact of factors associated with hypoxia, such as HIF1A (hypoxia-inducible factor 1-alpha) and VEGF (vascular endothelial growth factor), and with lipid metabolism, including PPARG (peroxisome proliferator-activated receptor-gamma), LXRA (liver X receptor-alpha) and LXRB (liver X receptor-beta), on the overall survival (OS) of CRC patients. Methods: This was a cohort study of 101 patients with high-risk stage II-III (TNM) CRC located above the peritoneal reflection. They were treated between 1990 and 2004 at the AC Camargo Cancer Center. Immunohistochemical analyses of HIF1A, VEGF, PPARG, LXRA and LXRB protein expression were performed using tissue microarrays (TMAs). Results: There was an association between the presence of vascular invasion and the lack of VEGF expression (p = 0. 028) as well as with positive HIF1A expression and lymphatic invasion (p = 0.045). The 5-year and 10-year OS rates were 76.6% and 60.2%, respectively. Patients with PPARG-positive tumors had a higher OS (p = 0.018). There were no correlations between the positive expression of VEGF, HIF1A, LXRA or LXRB and OS. The Cox regression model demonstrated that the risk of death was 2.72-fold higher in patients with PPARG-negative tumors (95% CI = 1.08­6.85). Conclusion: The PPARG expression was an independent prognostic factor for CRC tumors and might be used for risk stratification to stage II and stage III CRC patients (AU)

Hyperthermic Intraperitoneal Chemotherapy after Secondary Cytoreduction in Epithelial Ovarian Cancer: A Single-center Comparative Analysis.

BACKGROUND: Although the standard of care after recurrence of epithelial ovarian cancer (EOC) is chemotherapy, increasing data suggest that combining cytoreductive surgery with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising option for patients with recurrent EOC. Our aim was to determine the prognostic value of the addition of HIPEC to secondary cytoreductive surgery (SCR) in recurrent EOC. METHODS: We analyzed a series of 79 patients with platinum-sensitive recurrent EOC who were treated from May 2000 to January 2014. Fifty patients who underwent SCR were compared to 29 who had SCR in combination with HIPEC. RESULTS: The SCR group had a higher median age (58.4 years) compared to the SCR + HIPEC group (51.6 years) (p = 0.006). The median hospital stay length was longer for SCR + HIPEC versus SCR patients (11 and 8 days, respectively; p = 0.009). More subjects experienced National Cancer Institute grade III-IV morbidity in the SCR + HIPEC group (34.5 %) compared to the SCR group (10.6 %) (p = 0.015). Conversely, there were no deaths in the SCR + HIPEC group and 2 (4.0 %) deaths the SCR group. The median disease-free survival did not differ between SCR and SCR + HIPEC patients (18.6 and 15.8 months, respectively; p = 0.82); nor did median overall survival (59.3 and 58.3 months, respectively; p = 0.95). The presence of carcinomatosis was the only variable that remained linked to a higher risk of recurrence and death in the multivariate analysis. CONCLUSIONS: Our data suggest that the addition of HIPEC to cytoreduction in patients with recurrent platinum-sensitive EOC does not improve survival.

Clinical and Molecular Characterization of Brazilian Patients Suspected to Have Lynch Syndrome.

Lynch syndrome (LS) accounts for 3-5% of all colorectal cancers (CRC) and is inherited in an autosomal dominant fashion. This syndrome is characterized by early CRC onset, high incidence of tumors in the ascending colon, excess of synchronous/metachronous tumors and extra-colonic tumors. Nowadays, LS is regarded of patients who carry deleterious germline mutations in one of the five mismatch repair genes (MMR), mostly in MLH1 and MSH2, but also in MSH6, PMS1 and PMS2. To comprehensively characterize 116 Brazilian patients suspected for LS, we assessed the frequency of germline mutations in the three minor genes MSH6, PMS1 and PMS2 in 82 patients negative for point mutations in MLH1 and MSH2. We also assessed large genomic rearrangements by MLPA for detecting copy number variations (CNVs) in MLH1, MSH2 and MSH6 generating a broad characterization of MMR genes. The complete analysis of the five MMR genes revealed 45 carriers of pathogenic mutations, including 25 in MSH2, 15 in MLH1, four in MSH6 and one in PMS2. Eleven novel pathogenic mutations (6 in MSH2, 4 in MSH6 and one in PMS2), and 11 variants of unknown significance (VUS) were found. Mutations in the MLH1 and MSH2 genes represented 89% of all mutations (40/45), whereas the three MMR genes (MSH6, PMS1 and PMS2) accounted for 11% (5/45). We also investigated the MLH1 p.Leu676Pro VUS located in the PMS2 interaction domain and our results revealed that this variant displayed no defective function in terms of cellular location and heterodimer interaction. Additionally, we assessed the tumor phenotype of a subset of patients and also the frequency of CRC and extra-colonic tumors in 2,365 individuals of the 116 families, generating the first comprehensive portrait of the genetic and clinical aspects of patients suspected of LS in a Brazilian cohort.

Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries.

BACKGROUND: Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), postmeiotic segregation increased 1 (PMS1), post-meiotic segregation increased 2 (PMS2) and mutS homolog 6 (MSH6). Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected Lynch syndrome. METHODS: Blood samples from 88 patients were analyzed through sequencing MLH1, MSH2 and MSH6 genes. The probability of detecting a mutation was calculated using the PREMM, Barnetson, MMRpro, Wijnen and Myriad models. To evaluate the sensitivity and specificity of the models, receiver operating characteristic curves were constructed. RESULTS: Of the 88 patients included in this analysis, 31 mutations were identified: 16 were found in the MSH2 gene, 15 in the MLH1 gene and no pathogenic mutations were identified in the MSH6 gene. It was observed that the AUC for the PREMM (0.846), Barnetson (0.850), MMRpro (0.821) and Wijnen (0.807) models did not present significant statistical difference. The Myriad model presented lower AUC (0.704) than the four other models evaluated. Considering thresholds of ≥ 5%, the models sensitivity varied between 1 (Myriad) and 0.87 (Wijnen) and specificity ranged from 0 (Myriad) to 0.38 (Barnetson). CONCLUSIONS: The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models.

Characterization of germline mutations of MLH1 and MSH2 in unrelated south American suspected Lynch syndrome individuals.

Lynch syndrome (LS) is an autosomal dominant syndrome that predisposes individuals to development of cancers early in life. These cancers are mainly the following: colorectal, endometrial, ovarian, small intestine, stomach and urinary tract cancers. LS is caused by germline mutations in DNA mismatch repair genes (MMR), mostly MLH1 and MSH2, which are responsible for more than 85% of known germline mutations. To search for germline mutations in MLH1 and MSH2 genes in 123 unrelated South American suspected LS patients (Bethesda or Amsterdam Criteria) DNA was obtained from peripheral blood, and PCR was performed followed by direct sequencing in both directions of all exons and intron-exon junctions regions of the MLH1 and MSH2 genes. MLH1 or MSH2 pathogenic mutations were found in 28.45% (34/123) of the individuals, where 25/57 (43.85%) fulfilled Amsterdam I, II and 9/66 (13.63%) the Bethesda criteria. The mutations found in both genes were as follows: nonsense (35.3%), frameshift (26.47%), splicing (23.52%), and missense (9%). Thirteen alterations (35.14%) were described for the first time. The data reported in this study add new information about MLH1 and MSH2 gene mutations and contribute to better characterize LS in Brazil, Uruguay and Argentina. The high rate of novel mutations demonstrates the importance of defining MLH1 and MSH2 mutations in distinct LS populations.

Frequency of extracolonic tumors in Brazilian families with Lynch syndrome: analysis of a hereditary colorectal cancer institutional registry.

Lynch syndrome (LS) is caused by inherited germline mutations in mismatch repair (MMR) genes. It is one of the commonest forms of inherited predisposition to colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is characterized by early age of onset, with a tendency for multiplicity and an increased risk for extra-colonic tumors at particular sites. In this study we have evaluated the frequency of extra-colonic tumors in 60 unrelated LS families fulfilling the Amsterdam criteria (ACI. ACII) from the Oncotree database of the Hereditary Colorectal Cancer Registry of the AC Camargo Hospital. All families' pedigree was extensively analyzed, varying from 2 to 6 generations with a total of 2,095 individuals evaluated. As expected, colorectal cancer was the most frequent tumor in the families (334 cases). We found 200 extracolonic tumors among all individuals with a higher ratio in women (123 cases) than men (77 cases). By far, breast cancer (32 cases) was the most frequent extracolonic manifestation in women followed by endometrial (20 cases) and uterine cervix cancer (20 cases). For man, prostate (16 cases) and stomach (12 cases) cancer were the most frequent extracolonic tumors. It is well know that establishing the diagnosis is challenging and requires knowledge and surveillance. Thus, recognition of individuals and families with hereditary predisposition to cancer according to clinical and molecular features, combined with intensive surveillance and management programs, can contribute substantially to improve results related to the diagnosis and characterization of LS.

Câncer colorretal / Colorectal cancer

O câncer colorretal se destaca entre as neoplasias malignas mais incidentes no Brasil e no mundo. Estratégias de rastreamento incluem a pesquisa de sangue oculto nas fezes ou a colonoscopia, aplicadas às populações sob maior risco. A sintomatologia é pouco específica e a colonoscopia é o método ideal para diagnóstico, sendo indicada sempre que houver sinais e sintomas intestinais. O estadiamento define as modalidades de tratamento e é direcionado para as vias mais comuns da disseminação da doença: linfática, hematogênica, contiguidade e implantes. Quando o diagnóstico se faz em estádios iniciais, o tratamento do câncer colorretal proporciona elevadas taxas de cura. Este artigo resume de forma esquemática as modalidades atuais de tratamento, estratificadas em função do estadiamento.

Correlação clínico molecular em pacientes portadores de câncer pertencente a famílias com suspeita de Síndrome de Lynch / Clinical molecular correlation in patients with cancer related to a Lynch Syndrome suspected families

Introdução - A Síndrome de Lynch é uma doença hereditária que predispõe aos tumores colorretais, entre outros tumores, em idade precoce, com padrão de herança autossômica dominante, representando a principal causa de hereditária de câncer intestinal. Os genes de reparo defeituosos são responsáveis pela síndrome e podem ser identificados através dos testes de seqüenciamento dos genes. Os genes MLH1 e MSH2 são responsáveis por mais de 85% das mutações germinativas encontradas nestas famílias. O restante são causadas por outros genes de menor incidência, MSH6 e PMS2. A correlação clínico-molecular foi avaliada mais extensivamente em populações norte-americanas, com poucos estudos com a população brasileira. Objetivos - Este estudo tem como objetivo avaliar a correlação clínico-molecular de dados referentes aos pacientes com suspeita de SL, assim como de dados de membros da família com câncer relacionados à síndrome. Materiais e métodos – foram estudados 43 pacientes probandos e os familiares selecionados a partir de casuística do Hospital A.C. Camargo que preenchiam os critérios clínicos para SL, Amsterdam I ou II e também pacientes com critérios de Bethesda que apresentassem mutação em qualquer dos genes de reparo. Todos os pacientes foram submetidos a pesquisa de mutações, por seqüenciamento direto, nos genes MLH1 e MSH2 e nos casos inconclusivos foram avaliados também para os genes MSH6 e PMS2. As variáveis clínicas, anatomopatológicas e dados familiares foram correlacionados com as informações obtidas dos estudos moleculares. Para a averiguação de associações entre variáveis foi realizada análise univariada, através do teste qui-quadrado ou exato de Fisher, e a sobrevida dos pacientes probandos através do método de Kaplan-Meier. Resultados - A freqüência de identificação de mutação patogênica nos genes de reparo foi de 60,2%, em 26 probandos...

Familial adenomatous polyposis: data from the Hereditary Colorectal Cancer Registry (HCCR)

Family adenomatous polyposis (FAP) is a dominant autossomic disease responsible for nearly 1% of colorectal cancer (CRC) cases caused by mutations in gene APC and nearly complete penetrance. The identification of germinative mutations can be useful in the definition of the therapeutic conduct by means of the correlation genotype-phenotype. Objective: To describe clinical and molecular characteristics of families with FAP or attenuated FAP. Method: The study included families registered in the Hereditary Colorectal Cancer Registry of A.C.Camargo Hospital. Cancer records were registered and heredograms were created. Data were collected and stored in a database. Results: From 1992 to 2007 22 families were registered that had FAP, 16 with classic FAP, nine with Gardner Syndrome, and 6 with attenuated FAP. From 604 individuals, 120 had polyposis, 62 CRC, 10 desmoid tumors, three breast tumors, two tumors of the stomach, two thyroid tumors and one with prostate tumor. From 22 families, three were submitted to molecular analysis and mutations were identified in gene APC. Discussion: Half of the individuals presented CRC concomitant to polyposis, which can indicate a late diagnostic of the disease; three identified mutations presented correlations genotype-phenotype as predicted by the literature. Follow-up of patients with FAP, although they account for less than 1% of CRC cases, is vital for early cancer diagnosis.

P16 and p27 Immunohistochemical Expression in Colorectal Cancer: Analysis of 128 Patients

P16 and p27 are inhibiting proteins of cyclin-dependent kinases (CDKIs) that act in the restriction points of the cellular cycle, and it avoids its progression to DNA verification and repair by the cellular apparatus. This way, there should be, physiologically, an inverse relation between the expression of these proteins and cellular proliferation. However, what is really observed are changeable amounts of p27 in normal and tumor tissues. P16 participation in tumorigenesis is controversial. The expression of p16 and p27 as a prognostic factor in colorectal cancer (CRC) patients is controversial. Objetive: To establish a correlation between p16 and p27 immunohistochemical expressions with clinical and anatomopathological variable from patients with CRC. Material and methods: descriptive and retrospective study, with 128 CRC patients, treated surgically between 2000 and 2004, with available material for immunohistochemical analysis through standardized methods. The association between categorical variables was done using Chi-square, Pearson or Fisher?s Exact tests, and the continuous variables were analyzed by t-Student. Global survival and disease-free period were calculated according to Kaplan-Meier method and the associations through log-rank test. Results: The average follow-up time of patients was 35 months. Positivity of p16 was detected in 100% of cases. Negativity of p27 in 6.3% (n=8) of cases, with a significant association (p30.05) between p27 negative and tumors located in right colon (62.5%, n=5) and mucinous (62.5%, n=5). The average global survival was 54.8 months, and the significant clinical and pathological variables associated to survival were: better for curative surgeries; better for early stages; better for well-differentiated tumors; worse for cases with sanguineous or vascular lymphatic invasion; worse for perineural invasion. Conclusions: p27 negative is more frequent in right colon...