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OBJECTIVE: In the emergency care of cancer patients, in addition to cancer-related factors, two aspects influence the outcome: (1) where the patient is treated and (2) who will perform the surgery. In Brazil, a significant proportion of patients with surgical oncological emergencies will be operated on in general hospitals by surgeons without training in oncological surgery. OBJECTIVE: The objective was to discuss quality indicators and propose the creation of an urgent oncological surgery advanced life support course. METHODS: Review of articles on the topic. RESULTS: Generally, nonelective resections are associated with higher rates of morbidity and mortality, as well as lower rates of cancer-specific survival. In comparison to elective procedures, the reduced number of harvested lymph nodes and the higher rate of positive margins suggest a compromised degree of radicality in the emergency scenario. CONCLUSION: Among modifiable factors is the training of the emergency surgeon. Enhancing the practice of oncological surgery in emergency settings constitutes a formidable undertaking that entails collaboration across various medical specialties and warrants endorsement and support from medical societies and educational institutions. It is time to establish a national registry encompassing oncological emergencies, develop quality indicators tailored to the national context, and foster the establishment of specialized training programs aimed at enhancing the proficiency of physicians serving in emergency services catering to cancer patients.
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Neoplasias , Humanos , Neoplasias/cirugía , Indicadores de Calidad de la Atención de Salud , Brasil , Oncología Quirúrgica/normas , Oncología Quirúrgica/educación , Urgencias MédicasRESUMEN
SUMMARY In the emergency care of cancer patients, in addition to cancer-related factors, two aspects influence the outcome: (1) where the patient is treated and (2) who will perform the surgery. In Brazil, a significant proportion of patients with surgical oncological emergencies will be operated on in general hospitals by surgeons without training in oncological surgery. OBJECTIVE: The objective was to discuss quality indicators and propose the creation of an urgent oncological surgery advanced life support course. METHODS: Review of articles on the topic. RESULTS: Generally, nonelective resections are associated with higher rates of morbidity and mortality, as well as lower rates of cancer-specific survival. In comparison to elective procedures, the reduced number of harvested lymph nodes and the higher rate of positive margins suggest a compromised degree of radicality in the emergency scenario. CONCLUSION: Among modifiable factors is the training of the emergency surgeon. Enhancing the practice of oncological surgery in emergency settings constitutes a formidable undertaking that entails collaboration across various medical specialties and warrants endorsement and support from medical societies and educational institutions. It is time to establish a national registry encompassing oncological emergencies, develop quality indicators tailored to the national context, and foster the establishment of specialized training programs aimed at enhancing the proficiency of physicians serving in emergency services catering to cancer patients.
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PURPOSE: Soft tissue sarcomas are rare malignant tumors. Liposarcoma constitutes the most frequent histological subtype of retroperitoneal sarcoma. The prognosis of soft tissue sarcomas depends on clinical and histologic characteristics. OBJECTIVE: Evaluate variables that may be related to the overall and local recurrence-free survival in patients with retroperitoneal liposarcoma and discuss the need for visceral resection en-bloc for tumors. METHODS: A retrospective analysis was conducted of the medical records of 60 patients seen between 1997 and 2017 who underwent surgical resection of retroperitoneal liposarcoma. RESULTS: The overall survival rate at 5 years of follow-up was 75.22% (95% confidence interval [CI] 0.58-0.86). The probability of a local recurrence-free survival at 5 years of follow-up was 26.04% (95% CI 0.11-0.44). The multivariate analysis showed that dedifferentiated or pleomorphic tumors and R2/fragmented resection were associated with a shorter time to recurrence. No other characteristics markedly influenced the overall survival (P > 0.05). CONCLUSION: Patients with dedifferentiated or pleomorphic tumors and incomplete resection were associated with higher local recurrence rates than others. This study reinforces the need for complete and en-bloc resection with organs when there is clear involvement or technical surgical difficulty to maintain the tumor integrity.
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Liposarcoma , Neoplasias Retroperitoneales , Sarcoma , Humanos , Estudios Retrospectivos , Liposarcoma/cirugía , Liposarcoma/patología , Neoplasias Retroperitoneales/cirugía , Sarcoma/cirugía , Sarcoma/patología , Pronóstico , Tasa de Supervivencia , Recurrencia Local de NeoplasiaRESUMEN
Werner's syndrome is caused by the inactivation of both WRN alleles and is characterized by premature aging and increased risk of neoplasms, especially those of mesenchymal origins, such as sarcomas. Given the characteristic genomic instability, patients with this syndrome are more susceptible to develop toxicities when exposed to cytotoxic agents, such as alkylators and anthracyclines. The impact of the monoallelic WRN mutation on treatment-associated toxicities is poorly understood. Here, we report a patient with locally advanced dedifferentiated liposarcoma of the retroperitoneum harboring a heterozygous germline inactivation mutation in the WRN gene, who was treated with a classic regimen of ifosfamide and doxorubicin and developed exacerbated and prolonged hematological and renal toxicities.
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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.
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Adenoma/patología , Poliposis Adenomatosa del Colon/patología , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/patología , Receptor beta de Estrógeno/metabolismo , Pólipos/patología , Adenoma/metabolismo , Adenoma/cirugía , Poliposis Adenomatosa del Colon/metabolismo , Poliposis Adenomatosa del Colon/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pólipos/metabolismo , Pólipos/cirugía , Pronóstico , Tasa de SupervivenciaRESUMEN
Leiomyosarcoma (LMS) of inferior vena cava (IVC) is a rare neoplasm affecting approximately 1/100,000 people. The prognosis is poor and potential curative intent occurs through challenging operations, such as vena cava resection, occasionally multivisceral when required, and vascular reconstruction. There are few retrospective series regarding this retroperitoneal neoplasm, and the aim of the present study was to discuss the experience at the São Paulo Cancer Institute and Clinics Hospital of University of São Paulo Medical School, São Paulo, Brazil. The current study is a retrospective review of 7 patients treated in the two tertiary hospitals between 2005 and 2013. Oncological and operative aspects were discussed, primarily regarding surgical aspects highlighting en bloc resection, vascular reconstruction, and the overall survival and recurrence rates. All the patients were treated with radical intent, 4 of whom underwent multivisceral resection, with the kidney being the most resected organ. The location of the IVC tumor was described using Kulaylat's description and the median tumor size was 10 cm. Vascular reconstruction was necessary in 4 patients. The overall survival rate at 3 and 5 years was 100, and 25%, respectively. The disease-free survival rate at 3 and 5 years was 57 and 20%, respectively. In conclusion, IVC LMS is a rare and severe retroperitoneal neoplasm, with multivisceral resections remaining a surgical challenge. The treatment requires numerous experienced surgeons and the impact of microscopic free margins remains unclear. Vascular reconstruction depends on several aspects regarding primarily the topography of the tumor.
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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)
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Humanos , Masculino , Femenino , Pronóstico , Inmunohistoquímica , Neoplasias Colorrectales , Análisis de Supervivencia , Estudios de Cohortes , Metabolismo de los Lípidos , HipoxiaRESUMEN
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.
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Adenosina Trifosfatasas/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Enzimas Reparadoras del ADN/genética , Proteínas de Unión al ADN/genética , Mutación de Línea Germinal , Proteínas de Neoplasias/genética , Adolescente , Adulto , Brasil , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Variaciones en el Número de Copia de ADN , Reparación de la Incompatibilidad de ADN , Femenino , Humanos , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto , Proteínas MutL , Adulto JovenRESUMEN
BACKGROUND: Topoisomerase 2 alpha (TOP2A), HER-2/neu, and survivin are genes that lie on chromosome 17 and correlate with the prognosis and prediction of target-driven therapy against tumors. In a previous study, we showed that TOP2A transcripts levels were significantly higher in soft tissue sarcomas (STS) than in benign tumors and desmoid-type fibromatoses (FM). Because these genes have been insufficiently examined in STS, we aimed to identify alterations in TOP2A and HER-2 expression by fluorescent in situ hybridization and immunohistochemistry, as well as that of survivin, and correlate them with clinicopathologic findings to assess their prognostic value. METHODS: Eighteen FM and 244 STS were included. Fluorescent in situ hybridization and immunohistochemistry were performed on a tissue microarray. RESULTS: TOP2A and survivin were more highly expressed in sarcomas than in FM. TOP2A was an independent predictor of an unfavorable prognosis; it was combined with formerly established prognostic factors (primarily histologic grade and tumor size at diagnosis) to create a prognostic index that evaluated overall survival. Gene amplification/polysomy (13%) did not correlate with protein overexpression. Survivin and HER-2 expression were not associated with patient outcomes. CONCLUSIONS: These findings might become valuable in the management of patients with STS and possibly in the prospective evaluation of responses to new target-driven therapies.
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Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Cromosomas Humanos Par 17/genética , Amplificación de Genes , Sarcoma/mortalidad , Sarcoma/patología , Adolescente , Adulto , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , ADN-Topoisomerasas de Tipo II/genética , ADN-Topoisomerasas de Tipo II/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Femenino , Fibroma/mortalidad , Fibroma/patología , Fibroma/terapia , Fibromatosis Agresiva/mortalidad , Fibromatosis Agresiva/patología , Fibromatosis Agresiva/terapia , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Hibridación Fluorescente in Situ , Proteínas Inhibidoras de la Apoptosis/genética , Proteínas Inhibidoras de la Apoptosis/metabolismo , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Proteínas de Unión a Poli-ADP-Ribosa , Pronóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Sarcoma/terapia , Sarcoma Sinovial/mortalidad , Sarcoma Sinovial/patología , Sarcoma Sinovial/terapia , Tasa de Supervivencia , Survivin , Adulto JovenRESUMEN
Historically, scleroderma and other collagenous diseases have been considered a relative contraindication to radiation. The literature has few studies describing poor outcomes and cosmesis in this situation and there are almost no data concerning about reirradiation and colagenosis. The authors describe a case of a patient with a soft tissue sarcoma in the arm submitted to conservative surgery. They describe the outcome, cosmesis and function of this rare twice-irradiated scleroderma patient.
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Humanos , Braquiterapia , Esclerodermia Sistémica , RadioterapiaRESUMEN
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.
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Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación de la Incompatibilidad de ADN , Mutación de Línea Germinal , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Argentina , Brasil , Codón sin Sentido , Neoplasias Colorrectales Hereditarias sin Poliposis/etnología , Análisis Mutacional de ADN , Mutación del Sistema de Lectura , Humanos , Homólogo 1 de la Proteína MutL , Mutación Missense , Reacción en Cadena de la Polimerasa , UruguayRESUMEN
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.
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Humanos , Metástasis de la Neoplasia/terapia , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/terapiaRESUMEN
INTRODUCTION AND OBJECTIVE: Neoadjuvant and adjuvant therapies for soft tissue sarcomas of the extremities are still controversial. The aim of this study was to analyze the results of a protocol of neoadjuvant chemoradiation therapy for extremity sarcomas. METHODS: A retrospective analysis was carried out in a consecutive series of 49 adult patients with advanced extremity soft tissue sarcomas that could not be resected with adequate margins during the primary resection. All patients were treated with a protocol of preoperative radiation therapy at a total dose of 30 Gy, concomitant with doxorubicin (60 mg/m(2)) chemotherapy. The main endpoints assessed were local recurrence-free survival, metastasis-free survival and overall survival. The median follow-up time was 32.1 months. RESULTS: The five-year local recurrence-free survival, metastasis-free survival and overall survival rates were 81.5%, 46.7% and 58.3%, respectively. For high-grade tumors, the five-year metastasis-free and overall survival rates were only 36.3% and 41.2%, respectively. Severe wound complications were observed in 41.8% of the patients who underwent surgery. These complications precluded adjuvant chemotherapy in 73.7% (14/19) of the patients eligible to receive it. CONCLUSIONS: In this study, neoadjuvant chemoradiation therapy was associated with a good local control rate, but the distant relapse-free rate and overall survival rate were still poor. The high rate of wound complications modified the planning of adjuvant treatment in most patients.
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Terapia Neoadyuvante/efectos adversos , Sarcoma/mortalidad , Neoplasias de los Tejidos Blandos/mortalidad , Adolescente , Adulto , Anciano , Quimioterapia Adyuvante/efectos adversos , Doxorrubicina/efectos adversos , Métodos Epidemiológicos , Extremidades , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Radioterapia Adyuvante/efectos adversos , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/terapia , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION AND OBJECTIVE: Neoadjuvant and adjuvant therapies for soft tissue sarcomas of the extremities are still controversial. The aim of this study was to analyze the results of a protocol of neoadjuvant chemoradiation therapy for extremity sarcomas. METHODS: A retrospective analysis was carried out in a consecutive series of 49 adult patients with advanced extremity soft tissue sarcomas that could not be resected with adequate margins during the primary resection. All patients were treated with a protocol of preoperative radiation therapy at a total dose of 30 Gy, concomitant with doxorubicin (60 mg/m²) chemotherapy. The main endpoints assessed were local recurrence-free survival, metastasis-free survival and overall survival. The median follow-up time was 32.1 months. RESULTS: The five-year local recurrence-free survival, metastasis-free survival and overall survival rates were 81.5 percent, 46.7 percent and 58.3 percent, respectively. For high-grade tumors, the five-year metastasis-free and overall survival rates were only 36.3 percent and 41.2 percent, respectively. Severe wound complications were observed in 41.8 percent of the patients who underwent surgery. These complications precluded adjuvant chemotherapy in 73.7 percent (14/19) of the patients eligible to receive it. CONCLUSIONS: In this study, neoadjuvant chemoradiation therapy was associated with a good local control rate, but the distant relapse-free rate and overall survival rate were still poor. The high rate of wound complications modified the planning of adjuvant treatment in most patients.
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Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Terapia Neoadyuvante/efectos adversos , Sarcoma/mortalidad , Neoplasias de los Tejidos Blandos/mortalidad , Quimioterapia Adyuvante/efectos adversos , Doxorrubicina/efectos adversos , Métodos Epidemiológicos , Extremidades , Recurrencia Local de Neoplasia , Radioterapia Adyuvante/efectos adversos , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/terapia , Resultado del Tratamiento , Adulto JovenRESUMEN
Lynch syndrome represents 1-7% of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2); mutL homolog 1 (MLH1); mutS homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2); and postmeiotic segregation increased 1 (PMS1). It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3), also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors), approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50%) and MSH2 (40%), while others account for 10%. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.
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Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación de la Incompatibilidad de ADN/genética , Mutación de Línea Germinal/genética , HumanosRESUMEN
Lynch syndrome represents 1-7 percent of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2); mutL homolog 1 (MLH1); mutS homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2); and postmeiotic segregation increased 1 (PMS1). It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3), also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors), approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50 percent) and MSH2 (40 percent), while others account for 10 percent. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.
A síndrome de Lynch representa de 1-7 por cento de todos os casos de câncer colorretal. É uma síndrome de herança autossômica dominante que predispõe ao câncer e é causada por mutações nos genes de reparo de ácido desoxirribonucléico (DNA). Desde a descoberta dos principais genes com função de reparo de DNA, mutações nos genes MSH2, MLH1, MSH6, PMS2 e PMS1 estão relacionadas com a susceptibilidade à síndrome de Lynch. Outro gene, MLH3, tem sido proposto como tendo papel na predisposição à síndrome de Lynch, porém mutações de significância clínica nesse gene não são claras. De acordo com o banco de dados InSiGHT (International Society for Gastrointestinal Hereditary Tumors), aproximadamente 500 diferentes mutações associadas à síndrome de Lynch são conhecidas, envolvendo primeiramente MLH1 (50 por cento), MSH2 (40 por cento) e outros (10 por cento). Grandes progressos têm ocorrido para nosso entendimento das bases moleculares da síndrome de Lynch. A caracterização molecular será a forma mais precisa para definirmos a síndrome de Lynch e irá fornecer informações preditivas mais precisas sobre o risco de câncer colorretal e extra-colônico, além de permitir regimes otimizados de manejo.
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Humanos , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación de la Incompatibilidad de ADN/genética , Mutación de Línea Germinal/genéticaRESUMEN
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.
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Humanos , Colon , Herencia , Neoplasias , Pólipos Adenomatosos , RectoRESUMEN
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...