RESUMO
ABSTRACT Purpose To assess the relationship between De Ritis (aspartate aminotransaminase [AST]/Alanine aminotransaminase [ALT]) ratio and pathological variables and whether it is an independent prognostic factor. Materials and Methods We analyzed 298 consecutive patients who underwent radical or partial nephrectomy for non-metastatic renal cell carcinoma (RCC) between 2006 and 2015. The association between De Ritis ratio and pathological variables including tumor size, presence of renal vein invasion, vena cava invasion, renal capsule infiltration, Gerota fascia invasion, renal sinus involvement, renal pelvic invasion, angiolymphatic invasion, adrenal gland involvement, lymph node involvement, tumor necrosis, and Fuhrman's grade was tested. Multivariable Cox analysis was performed to evaluate the impact of this ratio on overall survival and cancer-specific survival. Results An increased preoperative De Ritis ratio was significantly associated with renal vein invasion, renal capsule infiltration and renal pelvis involvement (p<0.05) in non-metastatic RCC. On multivariate analysis we found that tumor size, Fuhrman grade and lymph node involvement were independent prognostic factors for cancer-specific survival. AST/ALT ratio had no influence on the risk of overall and cancer-specific survival. Conclusion An increased preoperative AST/ALT ratio had a significant association with renal vein invasion, renal capsule infiltration and renal pelvis involvement in patients with non-metastatic RCC. However, it does not appear to be an independent prognostic marker in non-metastatic RCC.
Assuntos
Humanos , Masculino , Feminino , Adulto , Idoso , Aspartato Aminotransferases/sangue , Carcinoma de Células Renais/enzimologia , Alanina Transaminase/sangue , Neoplasias Renais/enzimologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Biomarcadores Tumorais/sangue , Análise de Sobrevida , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de NeoplasiasRESUMO
Renal medullary carcinomas (RMCs) and collecting duct carcinomas (CDCs) are rare subsets of lethal high-stage, high-grade distal nephron-related adenocarcinomas with a predilection for the renal medullary region. Recent findings have established an emerging group of fumarate hydratase (FH)-deficient tumors related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC-RCCs) syndrome within this morphologic spectrum. Recently developed, reliable ancillary testing has enabled consistent separation between these tumor types. Here, we present the clinicopathologic features and differences in the morphologic patterns between RMC, CDC, and FH-deficient RCC in consequence of these recent developments. This study included a total of 100 cases classified using contemporary criteria and ancillary tests. Thirty-three RMCs (SMARCB1/INI1-deficient, hemoglobinopathy), 38 CDCs (SMARCB1/INI1-retained), and 29 RCCs defined by the FH-deficient phenotype (FH/2SC or FH/2SC with FH mutation, regardless of HLRCC syndromic stigmata/history) were selected. The spectrum of morphologic patterns was critically evaluated, and the differences between the morphologic patterns present in the 3 groups were analyzed statistically. Twenty-five percent of cases initially diagnosed as CDC were reclassified as FH-deficient RCC on the basis of our contemporary diagnostic approach. Among the different overlapping morphologic patterns, sieve-like/cribriform and reticular/yolk sac tumor-like patterns favored RMCs, whereas intracystic papillary and tubulocystic patterns favored FH-deficient RCC. The tubulopapillary pattern favored both CDCs and FH-deficient RCCs, and the multinodular infiltrating papillary pattern favored CDCs. Infiltrating glandular and solid sheets/cords/nested patterns were not statistically different among the 3 groups. Viral inclusion-like macronucleoli, considered as a hallmark of HLRCC-RCCs, were observed significantly more frequently in FH-deficient RCCs. Despite the overlapping morphology found among these clinically aggressive infiltrating high-grade adenocarcinomas of the kidney, reproducible differences in morphology emerged between these categories after rigorous characterization. Finally, we recommend that definitive diagnosis of CDC should only be made if RMC and FH-deficient RCC are excluded.
Assuntos
Biomarcadores Tumorais/deficiência , Carcinoma de Células Renais/patologia , Fumarato Hidratase/deficiência , Medula Renal/patologia , Neoplasias Renais/patologia , Túbulos Renais Coletores/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Biomarcadores Tumorais/genética , Biópsia , Brasil , Canadá , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/enzimologia , Carcinoma de Células Renais/genética , Criança , Análise Mutacional de DNA , Diagnóstico Diferencial , Europa (Continente) , Feminino , Fumarato Hidratase/genética , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Medula Renal/enzimologia , Neoplasias Renais/classificação , Neoplasias Renais/enzimologia , Neoplasias Renais/genética , Túbulos Renais Coletores/enzimologia , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Fenótipo , Valor Preditivo dos Testes , Estudos Retrospectivos , Estados Unidos , Adulto JovemRESUMO
PURPOSE: To assess the relationship between De Ritis (aspartate aminotransaminase [AST]/Alanine aminotransaminase [ALT]) ratio and pathological variables and whether it is an independent prognostic factor. MATERIALS AND METHODS: We analyzed 298 consecutive patients who underwent radical or partial nephrectomy for non-metastatic renal cell carcinoma (RCC) between 2006 and 2015. The association between De Ritis ratio and pathological variables including tumor size, presence of renal vein invasion, vena cava invasion, renal capsule infiltration, Gerota fascia invasion, renal sinus involvement, renal pelvic invasion, angiolymphatic invasion, adrenal gland involvement, lymph node involvement, tumor necrosis, and Fuhrman's grade was tested. Multivariable Cox analysis was performed to evaluate the impact of this ratio on overall survival and cancer-specific survival. RESULTS: An increased preoperative De Ritis ratio was significantly associated with renal vein invasion, renal capsule infiltration and renal pelvis involvement (p<0.05) in non-metastatic RCC. On multivariate analysis we found that tumor size, Fuhrman grade and lymph node involvement were independent prognostic factors for cancerspecific survival. AST/ALT ratio had no influence on the risk of overall and cancerspecific survival. CONCLUSION: An increased preoperative AST/ALT ratio had a significant association with renal vein invasion, renal capsule infiltration and renal pelvis involvement in patients with non-metastatic RCC. However, it does not appear to be an independent prognostic marker in non-metastatic RCC.
Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Carcinoma de Células Renais/enzimologia , Neoplasias Renais/enzimologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Análise de SobrevidaRESUMO
The survival of infective larvae (L3) of Trichostrongylus colubriformis was evaluated on Brachiaria, Coast-cross and Aruana forage grasses. Feces of sheep parasitized exclusively by T. colubriformis were deposited in winter and spring on experimental plots whose grasses were cut at two heights: 5 cm and 30 cm. One, two, four, eight, 12 and 16 weeks after depositing the feces, fecal and forage samples were collected for the retrieval and quantification of L3. Retrieval of L3 from feces and forage was negligible in winter due to the dry weather, although a few larvae were retrieved in the last larval collections. However, L3 retrieval from fecal samples was greater in spring, especially two weeks after feces were deposited on 30 cm high grasses. At this time, the L3 retrieval rate from the three forage grasses differed significantly (P <0.05), with Aruana grass showing the highest average L3 retrieval rate, followed by Coast-cross and Brachiaria. In conclusion, the winter drought proved very unfavorable for the presence of L3 in the environment, and the microclimate of Aruana pastureland was generally the most favorable for the retrieval of infective larvae.
A sobrevivência de larvas infectantes (L3) de Trichostrongylus colubriformis foi avaliada em pastagem de Braquiária, Coast-cross e Aruana. Fezes de ovinos parasitados exclusivamente por T. colubriformis foram depositadas no inverno e na primavera em parcelas experimentais com duas alturas de corte da forragem, 5 cm e 30 cm. Uma, duas, quatro, oito, 12 e 16 semanas após o depósito, amostras de fezes e de forragem foram coletadas para a recuperação e quantificação de L3. Devido à seca no inverno, a recuperação de L3 das fezes e da forragem foi ínfima, embora tenha havido recuperação de algumas larvas nas últimas coletas. Por outro lado, na primavera houve maior recuperação de L3 das amostras, especialmente duas semanas após a deposição das fezes em meio às pastagens com 30 cm de altura. Nesse momento, houve diferença significativa (P<0,05) entre as três forrageiras, com maior média de L3 no capim Aruana, seguido de Coast-cross e Braquiária. Em conclusão, a seca registrada no período de inverno se mostrou bastante desfavorável à presença de L3 no ambiente e, de forma geral, o microclima da pastagem de Aruana foi o que mais favoreceu a recuperação de larvas infectantes.
Assuntos
Humanos , Antimetabólitos Antineoplásicos/farmacologia , Carcinoma de Células Renais/enzimologia , Floxuridina/farmacologia , Fluoruracila/farmacologia , Neoplasias Renais/enzimologia , Timidina Fosforilase/metabolismo , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Rim/enzimologia , Valores de ReferênciaRESUMO
The survival of infective larvae (L3) of Trichostrongylus colubriformis was evaluated on Brachiaria, Coast-cross and Aruana forage grasses. Feces of sheep parasitized exclusively by T. colubriformis were deposited in winter and spring on experimental plots whose grasses were cut at two heights: 5 cm and 30 cm. One, two, four, eight, 12 and 16 weeks after depositing the feces, fecal and forage samples were collected for the retrieval and quantification of L3. Retrieval of L3 from feces and forage was negligible in winter due to the dry weather, although a few larvae were retrieved in the last larval collections. However, L3 retrieval from fecal samples was greater in spring, especially two weeks after feces were deposited on 30 cm high grasses. At this time, the L3 retrieval rate from the three forage grasses differed significantly (P <0.05), with Aruana grass showing the highest average L3 retrieval rate, followed by Coast-cross and Brachiaria. In conclusion, the winter drought proved very unfavorable for the presence of L3 in the environment, and the microclimate of Aruana pastureland was generally the most favorable for the retrieval of infective larvae.
A sobrevivência de larvas infectantes (L3) de Trichostrongylus colubriformis foi avaliada em pastagem de Braquiária, Coast-cross e Aruana. Fezes de ovinos parasitados exclusivamente por T. colubriformis foram depositadas no inverno e na primavera em parcelas experimentais com duas alturas de corte da forragem, 5 cm e 30 cm. Uma, duas, quatro, oito, 12 e 16 semanas após o depósito, amostras de fezes e de forragem foram coletadas para a recuperação e quantificação de L3. Devido à seca no inverno, a recuperação de L3 das fezes e da forragem foi ínfima, embora tenha havido recuperação de algumas larvas nas últimas coletas. Por outro lado, na primavera houve maior recuperação de L3 das amostras, especialmente duas semanas após a deposição das fezes em meio às pastagens com 30 cm de altura. Nesse momento, houve diferença significativa (P<0,05) entre as três forrageiras, com maior média de L3 no capim Aruana, seguido de Coast-cross e Braquiária. Em conclusão, a seca registrada no período de inverno se mostrou bastante desfavorável à presença de L3 no ambiente e, de forma geral, o microclima da pastagem de Aruana foi o que mais favoreceu a recuperação de larvas infectantes.
Assuntos
Humanos , Antimetabólitos Antineoplásicos/farmacologia , Carcinoma de Células Renais/enzimologia , Floxuridina/farmacologia , Fluoruracila/farmacologia , Neoplasias Renais/enzimologia , Timidina Fosforilase/metabolismo , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Rim/enzimologia , Valores de ReferênciaRESUMO
INTRODUCTION: The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC) is evolving, and Carbonic Anhydrase type IX (CA-IX) has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1) overall survival, and 2) with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion). MATERIALS AND METHODS: This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS), TNM stage, tumor size (TS), Fuhrman nuclear grade (FNG), microvascular invasion (MVI), peri-renal fat invasion (PFI). We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop ® software. RESULTS: The mean follow-up time was 7.9 years (range 1.9 to 19.5 years). The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790); T stage (p = 0.179); tumor size (p = 0.143); grouped Fuhrman nuclear grade (p = 0.598); microvascular invasion (p = 0.685), and peri-renal fat invasion (p = 0.104). CONCLUSION: Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma.
Assuntos
Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Anidrases Carbônicas/análise , Carcinoma de Células Renais/enzimologia , Neoplasias Renais/enzimologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anidrase Carbônica IX , Carcinoma de Células Renais/patologia , Criança , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo , Análise Serial de Tecidos/métodos , Carga Tumoral , Adulto JovemRESUMO
Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC) is evolving, and Carbonic Anhydrase type IX (CA-IX) has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1) overall survival, and 2) with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion). Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS), TNM stage, tumor size (TS), Fuhrman nuclear grade (FNG), microvascular invasion (MVI), peri-renal fat invasion (PFI). We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years). The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790); T stage (p = 0.179); tumor size (p = 0.143); grouped Fuhrman nuclear grade (p = 0.598); microvascular invasion (p = 0.685), and peri-renal fat invasion (p = 0.104). Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma. .
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antígenos de Neoplasias/análise , Anidrases Carbônicas/análise , Carcinoma de Células Renais/enzimologia , Neoplasias Renais/enzimologia , Biomarcadores Tumorais/análise , Carcinoma de Células Renais/patologia , Imuno-Histoquímica , Neoplasias Renais/patologia , Gradação de Tumores , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo , Carga Tumoral , Análise Serial de Tecidos/métodosRESUMO
Integrin-linked kinase (ILK) is an unique intracellular serine/threonine kinase and adapter protein. When dysregulated, it has been associated with increased cell proliferation, anchorage-independent cell growth, evasion of apoptosis, angiogenesis, invasion of surrounding tissues, downregulation of E-cadherin expression, nuclear translocation of ß-catenin and metastasis, all features of tumoral malignancy. The objective of the present work was to evaluate the expression of ILK in clear cell renal carcinomas (CCRC) as a possible prognostic indicator. ILK immunoexpression was evaluated in a tissue microarray (TMA) with 45 human CCRCs. In addition, the apoptotic and proliferative indices and the immuno-expression of ß-catenin and E-cadherin were also evaluated. E-cadherin expression was significantly decreased in tumors with positive ILK expression in relation to those with negative immunoexpression (p = 0.011). ILK immunostaining was significantly increased in high-grade in comparison to low-grade CCRCs (p = 0.0008). ILK expression was also associated with increased proliferative index (p = 0.020), tumor size >7.0 cm (p = 0.018) and with renal vein and capsule invasion (p = 0.003 and p = 0.00). Finally, tumors stage I and II (noninvasive) presented significantly reduced ILK immunoexpression when compared to stage III (locally invasive) (p = 0.0028). ILK immunoexpression in CCRC increases with loss of intercellular adhesion, nuclear grading, increased proliferative index and Robson stage. Altogether, our data suggest a possible role for ILK in the progression of CRCC.
Assuntos
Carcinoma de Células Renais/enzimologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/enzimologia , Neoplasias Renais/patologia , Proteínas Serina-Treonina Quinases/biossíntese , Apoptose/fisiologia , Caderinas/metabolismo , Carcinoma de Células Renais/química , Processos de Crescimento Celular/fisiologia , Humanos , Imuno-Histoquímica , Neoplasias Renais/metabolismo , Gradação de Tumores , Proteínas Serina-Treonina Quinases/metabolismo , Estatísticas não Paramétricas , Análise Serial de Tecidos , beta Catenina/metabolismoAssuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Metaloproteinase 1 da Matriz/genética , Regiões Promotoras Genéticas , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Carcinoma de Células Renais/enzimologia , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Neoplasias Renais/enzimologia , Polimorfismo de Fragmento de RestriçãoRESUMO
OBJECTIVE: Investigate the possible association of insertion/deletion (2G/G) polymorphism at nucleotide -1607 of the MMP-1 promoter with the development and progression of renal cancer. MATERIALS AND METHODS: In this study, we genotyped 217 individuals, 99 patients with renal cell carcinoma (RCC) and 118 controls without cancer. DNA specimens were extracted from epithelial buccal cells and paraffin-embedded tissue of RCC patients and from epithelial buccal cells and blood cells of healthy controls. RESULTS: The difference in frequency of 2G/2G genotype between controls (22.9%) and RCC patients (28.6%) was not statistically significant (p = 0.461). We also did not find correlation between 2G/2G and histological type of RCC. The comparison of genotype distribution and frequency of 2G allele in different populations showed a strong variability of 2G allele frequency among the different ethnic groups. This fact may influence on the collaboration of this 2G allele in RCC or others diseases. CONCLUSION: Our data suggest that the matrix metalloproteinase-1 (MMP-1) promoter polymorphism may not play a significant role in renal cell carcinoma patients in Brazil.
Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Metaloproteinase 1 da Matriz/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Carcinoma de Células Renais/enzimologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Renais/enzimologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de RestriçãoRESUMO
OBJECTIVE: Investigate the possible association of insertion/deletion (2G/G) polymorphism at nucleotide -1607 of the MMP-1 promoter with the development and progression of renal cancer MATERIALS AND METHODS: In this study, we genotyped 217 individuals, 99 patients with renal cell carcinoma (RCC) and 118 controls without cancer. DNA specimens were extracted from epithelial buccal cells and paraffin-embedded tissue of RCC patients and from epithelial buccal cells and blood cells of healthy controls RESULTS: The difference in frequency of 2G/2G genotype between controls (22.9 percent) and RCC patients (28.6 percent) was not statistically significant (p = 0.461). We also did not find correlation between 2G/2G and histological type of RCC. The comparison of genotype distribution and frequency of 2G allele in different populations showed a strong variability of 2G allele frequency among the different ethnic groups. This fact may influence on the collaboration of this 2G allele in RCC or others diseases CONCLUSION: Our data suggest that the matrix metalloproteinase-1 (MMP-1) promoter polymorphism may not play a significant role in renal cell carcinoma patients in Brazil.