RESUMO
Diagnosis of colorectal cancer in patients under 45 years old should alert us to possible hereditary forms of this neoplasia. Most cases of hereditary colorectal cancer correspond to Lynch syndrome which is caused by mutations in DNA mismatch repair genes, particularly MLH1 and MSH2. The dysfunction is associated with microsatellite instability which occurs in 95% cases of this syndrome and in 15% of sporadic colorectal cancer. In sporadic colon tumors, downregulation of MLH1 is observed in cases with the BRAF V600E variant, which induces hypermetylation of the MLH1 promoter. Mutation screening for hereditary cancer has impacted the diagnosis, genetic counseling, and early tumor detection in families affected by hereditary colorectal cancer syndromes but mutation screening technologies are seldom available in public health care centers in developing countries. This study aimed to describe immunohistochemistry and microsatellite instability abnormalities in tumor samples archived in a public hospital in Mexico. Paraffin-embedded samples of patients with colorectal cancer, diagnosed at under 50 years old, were studied to analyze correlations among clinical variables, MLH1 and MSH2 protein expression (immunohistochemistry), microsatellite instability (fluorescent PCR-based assay), and BRAF V600E variant (real time PCR). Forty-seven tumor specimens from patients with TNM stage II and above were analyzed. Tumors were mainly located in the proximal colon segment and displayed histologic intestinal variety and infiltration to serosa. Twenty samples showed decreased expression of mismatch repair proteins and 10 of these presented microsatellite instability (7 high and 3 low instability patterns, respectively). There were no instances of BRAF V600E mutation found. Altered MLH1 or MSH2 expression was found in 42.5% of the samples and microsatellite instability was observed in 21.3% of the tumors. These results suggested that about a fifth of the patients were candidates for family assessment and genetic counseling.
Assuntos
Animais , Masculino , Camundongos , Medula Óssea/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Floxuridina/toxicidade , Imunossupressores/toxicidade , Timo/patologia , Peso Corporal/efeitos dos fármacos , Corticosterona/sangue , Desoxicitidina/toxicidade , Relação Dose-Resposta a Droga , Imuno-Histoquímica , Isomerismo , Tamanho do Órgão/efeitos dos fármacos , Contagem de Reticulócitos/efeitos dos fármacosRESUMO
Chronic inflammation and infection are major risk factors for gastric carcinogenesis in adults. As chronic gastritis is common in Mexican children, diagnosis of Helicobacter pylori and other causes of gastritis are critical for the identification of children who would benefit from closer surveillance. Antral biopsies from 82 Mexican children (mean age, 8.3 ± 4.8 years) with chronic gastritis (36 H pylori+, 46 H pylori-) were examined for gastritis activity, atrophy, intestinal metaplasia (IM), and immunohistochemical expression of gastric carcinogenesis biomarkers caudal type homeobox 2 (CDX2), ephrin type-B receptor 4 (EphB4), matrix metalloproteinase 3 (MMP3), macrophage migration inhibitory factor (MIF), p53, ß-catenin, and E-cadherin. Atrophy was diagnosed in 7 (9%) of 82, and IM, in 5 (6%) of 82 by routine histology, whereas 6 additional children (7%) (3 H pylori+) exhibited aberrant CDX2 expression without IM. Significant positive correlations were seen between EphB4, MMP3, and MIF (P<.0001). Atrophy and follicular pathology were more frequent in H pylori+ biopsies (P<.0001), whereas IM and CDX2 expression showed no significant correlation with H pylori status. Antral biopsies demonstrating atrophy, IM, and/or aberrant CDX2 expression were seen in 21.95% (18/82) of the children, potentially identifying those who would benefit from closer surveillance and preventive dietary strategies. Biomarkers CDX2, EphB4, MMP3, and MIF may be useful in the workup of pediatric gastritis.
Assuntos
Gastrite/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori , Enteropatias/patologia , Lesões Pré-Cancerosas/patologia , Antro Pilórico/patologia , Adolescente , Idoso , Idoso de 80 Anos ou mais , Atrofia/epidemiologia , Atrofia/metabolismo , Atrofia/patologia , Biomarcadores/metabolismo , Criança , Pré-Escolar , Comorbidade , Feminino , Gastrite/epidemiologia , Gastrite/metabolismo , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/metabolismo , Humanos , Lactente , Enteropatias/epidemiologia , Enteropatias/metabolismo , Masculino , México , Pessoa de Meia-Idade , Vigilância da População , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/metabolismo , Antro Pilórico/metabolismoAssuntos
Mesotelioma/epidemiologia , Neoplasias Pleurais/epidemiologia , Adulto , Idoso , Amianto/efeitos adversos , Carcinoma Broncogênico/epidemiologia , Exposição Ambiental , Feminino , Inquéritos Epidemiológicos , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , México , Pessoa de Meia-Idade , Morbidade/tendências , Derrame Pleural/epidemiologia , Distribuição por Sexo , Tuberculose Pleural/epidemiologiaRESUMO
BACKGROUND AND AIMS: A third of colorectal carcinomas (CRC) affect patients <50 years of age. Fifteen percent of CRC cases with microsatellite instability are due to inherited germ-line mutations in DNA mismatch repair genes. The rest have an epigenetic hypermethylation of the MLH1 promoter in whom the BRAF V600E mutation is a common hallmark. Immunohistochemistry helps to classify colorectal cancers with 100% specificity and 92% sensitivity. We undertook this study to determine if age is a risk factor for defective MMR protein expression and BRAF mutations in our population and to compare these results with the histopathological tumor features. METHODS: Immunohistochemistry for MLH1 and MSH2 and RT-PCR BRAF V600E mutation was performed on tissue specimens from 57 patients <50 years of age. Data on age, gender, tumor location, histology, depth of infiltration, and the presence of metastatic lymph nodes were collected. Forty eight patients >50 years of age were used as a control group. A statistical analysis using ANOVA, χ(2), and Spearman's rho test were performed. RESULTS: Absent MMR protein expression was more prevalent in patients <50 years of age. No BRAF V600E mutations were detected in either group. Medullary and mucinous types were more prevalent among young patients, whereas intestinal type was more frequent in older patients (p = 0.0008). No differences were found regarding clinicopathological stages between groups. CONCLUSIONS: We found an association between young age and defective MMR expression. No V600E BRAF mutations were detected in either group.
Assuntos
Pareamento Incorreto de Bases , Neoplasias Colorretais/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Humanos , Imuno-Histoquímica , México , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: Germ cell testicular tumors have survival rate that diminishes with high tumor marker levels, such as human chorionic gonadotropin (hCG). hCG may regulate vascular neoformation through vascular endothelial growth factor (VEGF). Our purpose was to determine the relationship between hCG serum levels, angiogenesis, and VEGF expression in germ cell testicular tumors. METHODS: We conducted a retrospective study of 101 patients. Serum levels of hCG, alpha-fetoprotein (AFP), and lactate dehydrogenase were measured prior to surgery. Vascular density (VD) and VEGF tissue expression were determined by immunohistochemistry and underwent double-blind analysis. RESULTS: Histologically, 46% were seminomas and 54%, non-seminomas. Median follow-up was 43 +/- 27 months. Relapse was present in 7.5% and mortality in 11.5%. Factors associated with high VD included non-seminoma type (p = 0.016), AFP > or = 14.7 ng/mL (p = 0.0001), and hCG > or = 25 mIU/mL (p = 0.0001). In multivariate analysis, the only significant VD-associated factor was hCG level (p = 0.04). When hCG levels were stratified, concentrations > or = 25 mIU/mL were related with increased neovascularization (p < 0.0001). VEGF expression was not associated with VD or hCG serum levels. CONCLUSION: This is the first study that relates increased serum hCG levels with vascularization in testicular germ cell tumors. Hence, its expression might play a role in tumor angiogenesis, independent of VEGF expression, and may explain its association with poor prognosis. hCG might represent a molecular target for therapy.
Assuntos
Biomarcadores Tumorais/sangue , Gonadotropina Coriônica/sangue , Neoplasias Embrionárias de Células Germinativas/sangue , Neovascularização Patológica/patologia , Neoplasias Testiculares/sangue , Adulto , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/sangue , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/irrigação sanguínea , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Testiculares/irrigação sanguínea , Neoplasias Testiculares/patologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , alfa-Fetoproteínas/análiseRESUMO
Primary angiosarcoma of the spleen is rare and almost always fatal. The pathogenesis is unknown. It has an aggressive behavior and frequently presents with hematological abnormalities or metastatic disease. We report a 49 year-old male that presented with spleen and lymph node enlargement. He was subjected to a splenectomy and the biopsy disclosed an angiosarcoma of the spleen. Metastases were detected in the lung and bones and the patient was considered beyond any therapeutic option, dying fifteen months later.
Assuntos
Hemangiossarcoma/patologia , Neoplasias Esplênicas/patologia , Biópsia , Neoplasias Ósseas/secundário , Evolução Fatal , Hemangiossarcoma/secundário , Hemangiossarcoma/cirurgia , Humanos , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Baço/patologia , Esplenectomia , Neoplasias Esplênicas/cirurgiaRESUMO
Primary angiosarcoma of the spleen is rare and almost always fatal. The pathogenesis is unknown. It has an aggressive behavior and frequently presents with hematological abnormalities or metastatic disease. We report a 49 year-old male that presented with spleen and lymph node enlargement. He was subjected to a splenectomy and the biopsy disclosed an angiosarcoma of the spleen. Metastases were detected in the lung and bones and the patient was considered beyond any therapeutic option, dying fifteen months later.