Densidade microvascular e expressão do fator de crescimento endotelial vascular em uma série de 79 casos de tumores estromais gastrintestinais

Introdução: Tumores estromais gastrintestinais (GISTs) perfazem cerca de 70% dos tumores mesenquimais do trato gastrintestinal. Têm uma incidência de 1 a 2/100.000/ano sendo a forma esporádica observada em adultos, a mais comum. Para o diagnóstico definitivo de GIST é necessária a confirmação imunoistoquímica, sendo 90 a 95% dos casos positivos para o marcador CD117. Os GISTs apresentam comportamento biológico incerto e a classificação em categorias de risco (tamanho tumoral e índice mitótico – NIH) tem sido validada em inúmeras séries. Fatores angiogênicos como a DMV (densidade microvascular) e VEGF (fator de crescimento vascular endotelial) tem importância fundamental no crescimento e na progressão tumoral em algumas neoplasias e o seu significado nos GISTs ainda não está estabelecido. Objetivo: relacionar a expressão da densidade microvascular (DMV) e do marcador angiogênico VEGF com a curva de sobrevida dos pacientes portadores de GISTs. Material e Métodos: foram selecionados 79 casos diagnosticados como GIST, do Serviço de Patologia do Hospital de Clínica de Porto Alegre, no período de janeiro de 1.993 a dezembro de 2.009. Realizada a técnica da imunoistoquímica para avaliação do VEGF e do CD31 para avaliação da DMV. Os “hot spots” foram identificados em cada caso e a DMV avaliada através do método Chalkley computadorizado. Resultados: dos 79 casos, 14 foram obtidos através de biópsias e 65 de peças cirúrgicas. Todos os casos foram diagnosticados como GISTs esporádicos sendo 42 casos do sexo masculino e 37 do sexo feminino, com uma média de idade de 58,9 anos. A localização gástrica foi a mais frequente (45,6%) seguida pelo intestino delgado (38,0%). O tipo histológico predominante foi o fusocelular presente em 72,2% dos casos. GISTs classificados na categoria de risco muito baixo foram 15,4%, baixo risco 13,8%, risco intermediário 23,1% e alto risco 47,7%. Todos os casos apresentaram positividade para o VEGF, sendo que 27,8% foram considerados fracos positivos e 72,2% forte positivos. Na avaliação da DMV, 67 casos 84,8% apresentaram uma média de menos de 6 vasos marcados com CD31 e 15,2% apresentaram uma média de mais de seis vasos marcados. Houve diferença estatisticamente significativa na sobrevida de pacientes com DMV ≤ 6 vasos (média=11,2; IC 95%: 10,1 a 12,4) com os DMV≥ 6 vasos (média=2,4, IC 95%: 1,67 a 3,17), com P=0,001. Conclusões: 79 casos de GISTs diagnosticados no HCPA foram caracterizados do ponto de vista angiogênico. Houve associação da DMV com a sobrevida dos pacientes. O VEGF e a DMV não apresenta associação significativa com sexo, faixa etária, tipo histológico, categoria de risco, localização e metástases.Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, representing 70% of these neoplasias, having an annual incidence of 1 to 2/100.000. They are mostly sporadic and occurring mainly in adults. GISTs are tumors of relative unknown behavior and a score of risk stratification was developed based on two criteria: maximum tumor size and mitotic index according to the National Institutes of Health (NIH) consensus, validated by several authors. Angiogenic factors such as the MVD (microvessel density) and VEGF (vascular endothelial growth factor) may play an important role in growth and tumor progression, and its significance in GISTs remains unclear. Objective: to study the MVD and VEGF expression in GISTs and its correlation with the survival rate of these patients. Material and Methods: 79 cases of GISTs were diagnosed by the Pathology Service at the HCPA (Hospital de Clínicas de Porto Alegre) from January 1993 to December 2009 and submitted to immunohistochemical analysis for VEGF and CD31. For the MVD study,” hot spots” (CD31 positive vessels) were initially identified and the MVD evaluated by computational Chalkley method. Results: out of 79 GISTs, 14 cases were achieved from biopsies and 65 from surgical resections. All cases were diagnosed as sporadic GISTs, 42 male and 37 female with an average age of 58,9 years. GISTs were predominately located in the stomach (45,6%) followed by the small intestine (38,0%). Spindle cell morphology was present in 72, 2% of these tumors. According to the NIH classification, 15,4% GIST were classified as very low risk category, 13,8% low risk category, 23,1% intermediate risk category and 47,7% belonged to the high risk category. VEGF expression was seen all cases, 27, 8% were considered weakly positive and 72, 2% strongly positive. 67(84, 8%) GISTs showed an average of less than six vessels stained by CD31 (MVD) and 15, 2% GISTs an average of more than six vessels stained by CD31. A statistically significant difference was observed between the survival rate of patients having GISTs and the MVD: ≤ 6 vessels (mean=2,4, CI 95%: 1,67 a 3,17) and ≥ 6 vessels (mean=2,4, CI 95%: 1,67 a 3,17), p=0,001. Conclusions: 79 cases of GISTs diagnosed at the HCPA were studied for angiogenic factors. There was a statistically significant difference between MVD and the survival rate for these patients. No association for VEGF and MVD was seen when related to sex, age, histological type, risk category, location and metastasis

Densidade microvascular e expressão do fator de crescimento endotelial vascular em uma série de 79 casos de tumores estromais gastrintestinais

Introdução: Tumores estromais gastrintestinais (GISTs) perfazem cerca de 70% dos tumores mesenquimais do trato gastrintestinal. Têm uma incidência de 1 a 2/100.000/ano sendo a forma esporádica observada em adultos, a mais comum. Para o diagnóstico definitivo de GIST é necessária a confirmação imunoistoquímica, sendo 90 a 95% dos casos positivos para o marcador CD117. Os GISTs apresentam comportamento biológico incerto e a classificação em categorias de risco (tamanho tumoral e índice mitótico – NIH) tem sido validada em inúmeras séries. Fatores angiogênicos como a DMV (densidade microvascular) e VEGF (fator de crescimento vascular endotelial) tem importância fundamental no crescimento e na progressão tumoral em algumas neoplasias e o seu significado nos GISTs ainda não está estabelecido. Objetivo: relacionar a expressão da densidade microvascular (DMV) e do marcador angiogênico VEGF com a curva de sobrevida dos pacientes portadores de GISTs. Material e Métodos: foram selecionados 79 casos diagnosticados como GIST, do Serviço de Patologia do Hospital de Clínica de Porto Alegre, no período de janeiro de 1.993 a dezembro de 2.009. Realizada a técnica da imunoistoquímica para avaliação do VEGF e do CD31 para avaliação da DMV. Os “hot spots” foram identificados em cada caso e a DMV avaliada através do método Chalkley computadorizado. Resultados: dos 79 casos, 14 foram obtidos através de biópsias e 65 de peças cirúrgicas. Todos os casos foram diagnosticados como GISTs esporádicos sendo 42 casos do sexo masculino e 37 do sexo feminino, com uma média de idade de 58,9 anos. A localização gástrica foi a mais frequente (45,6%) seguida pelo intestino delgado (38,0%). O tipo histológico predominante foi o fusocelular presente em 72,2% dos casos. GISTs classificados na categoria de risco muito baixo foram 15,4%, baixo risco 13,8%, risco intermediário 23,1% e alto risco 47,7%. Todos os casos apresentaram positividade para o VEGF, sendo que 27,8% foram considerados fracos positivos e 72,2% forte positivos. Na avaliação da DMV, 67 casos 84,8% apresentaram uma média de menos de 6 vasos marcados com CD31 e 15,2% apresentaram uma média de mais de seis vasos marcados. Houve diferença estatisticamente significativa na sobrevida de pacientes com DMV ≤ 6 vasos (média=11,2; IC 95%: 10,1 a 12,4) com os DMV≥ 6 vasos (média=2,4, IC 95%: 1,67 a 3,17), com P=0,001. Conclusões: 79 casos de GISTs diagnosticados no HCPA foram caracterizados do ponto de vista angiogênico. Houve associação da DMV com a sobrevida dos pacientes. O VEGF e a DMV não apresenta associação significativa com sexo, faixa etária, tipo histológico, categoria de risco, localização e metástases.Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, representing 70% of these neoplasias, having an annual incidence of 1 to 2/100.000. They are mostly sporadic and occurring mainly in adults. GISTs are tumors of relative unknown behavior and a score of risk stratification was developed based on two criteria: maximum tumor size and mitotic index according to the National Institutes of Health (NIH) consensus, validated by several authors. Angiogenic factors such as the MVD (microvessel density) and VEGF (vascular endothelial growth factor) may play an important role in growth and tumor progression, and its significance in GISTs remains unclear. Objective: to study the MVD and VEGF expression in GISTs and its correlation with the survival rate of these patients. Material and Methods: 79 cases of GISTs were diagnosed by the Pathology Service at the HCPA (Hospital de Clínicas de Porto Alegre) from January 1993 to December 2009 and submitted to immunohistochemical analysis for VEGF and CD31. For the MVD study,” hot spots” (CD31 positive vessels) were initially identified and the MVD evaluated by computational Chalkley method. Results: out of 79 GISTs, 14 cases were achieved from biopsies and 65 from surgical resections. All cases were diagnosed as sporadic GISTs, 42 male and 37 female with an average age of 58,9 years. GISTs were predominately located in the stomach (45,6%) followed by the small intestine (38,0%). Spindle cell morphology was present in 72, 2% of these tumors. According to the NIH classification, 15,4% GIST were classified as very low risk category, 13,8% low risk category, 23,1% intermediate risk category and 47,7% belonged to the high risk category. VEGF expression was seen all cases, 27, 8% were considered weakly positive and 72, 2% strongly positive. 67(84, 8%) GISTs showed an average of less than six vessels stained by CD31 (MVD) and 15, 2% GISTs an average of more than six vessels stained by CD31. A statistically significant difference was observed between the survival rate of patients having GISTs and the MVD: ≤ 6 vessels (mean=2,4, CI 95%: 1,67 a 3,17) and ≥ 6 vessels (mean=2,4, CI 95%: 1,67 a 3,17), p=0,001. Conclusions: 79 cases of GISTs diagnosed at the HCPA were studied for angiogenic factors. There was a statistically significant difference between MVD and the survival rate for these patients. No association for VEGF and MVD was seen when related to sex, age, histological type, risk category, location and metastasis

Microvessel density (Chalkley method) in a series of 79 gastrointestinal stromal tumors

Background: Evaluation of the MVD (modified Chalkley method) in a series of 79 cases of GISTs diagnosed by the Pathology Service at the HCPA (Hospital de Clinicas de Porto Alegre) from January 1993 to December 2009. Methods: Seventy nine cases of GISTs were submitted to immunohistochemical analysis for CD31, an endothelial marker, to analyze MVD. Hot spots were identified for each case, and the mean numbers of stained blood vessels collected through Chalkley count, with the use of a 25 point grid, placed onto a scanned image. Images were analysed through an image analysis system. We used a cutoff of six vessels.Results: Our series was composed of 42 males and 37 females and presented an average age of 58.9 years. GISTs were predominately located in the stomach (45.6%) followed by the small intestine (38.0%). Sixty seven GISTs (84.8%) showed an average of less than six vessels stained by CD31 (MVD) and 12 (15.2%) GISTs an average of more than six vessels. A statistically significant difference was observed between survival rate of patients having GISTs with MVD of ≤ 6 vessels (mean = 2.4, CI 95%: 1.67 - 3.17) and patients having GISTs with MVD of ≥ 6 vessels (mean = 2.4, CI 95%: 1.67 - 3.17), P = 0.001. No association for MVD was observed related to sex, age, histological type, risk category, location and metastasis.Conclusions: Seventy nine cases of GISTs diagnosed at a single center in South Brazil were studied for MVD (Chalkley method). There was a statistically significant difference between MVD and the survival rate for these patients. The use of Chalkley method in GISTs may be helpful to evaluate clinical outcome