RESUMO
BACKGROUND: Several studies have suggested the significance of some metalloproteases in the malignant behaviour of hepatocellular carcinoma. AIMS: To evaluate the liver expression of MMPs and their tissular inhibitors in patients with HCC. METHODS: An immunohistochemical study using tissue microarrays on samples obtained from 30 HCC patients, with antibodies against MMPs (1, 2, 7, 9, 11, 13 and 14) and TIMPs (1, 2 and 3) was performed. Results were correlated with various clinico-pathological findings and with overall survival. RESULTS: MMP-1 is mainly expressed by stromal cells, and MMP-13, TIMP-1 and TIMP-2 by inflammatory cells. A positive correlation between MMP-1 expression and larger size tumours (p<0.01) was found. Increased TIMP-2 expression was associated with higher preoperative serum levels of alpha-fetoprotein (p<0.01). Unsupervised hierarchical clustering for total score values designated two groups, one of them characterised by high MMPs and TIMPs expressions, including 21 cases (70%) for tumour cell clustering, 5 cases for fibroblasts (16.6%) and 6 cases for inflammatory cells (20%). All patients showing elevated MMPs and TIMPs expression in stromal cells presented a poor prognosis (p<0.05). CONCLUSIONS: High liver MMPs and TIMPs expressions in peritumour stromal cells are related to a poorer prognosis in HCC.
Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Feminino , Seguimentos , Humanos , Fígado/citologia , Fígado/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Células Estromais/metabolismo , Análise de SobrevidaRESUMO
AIMS: To analyse the expression of metalloproteinases (MMPs) and their inhibitors (TIMPs) in ductal carcinoma in situ of the breast (DCIS). METHODS AND RESULTS: An immunohistochemical study was performed in 56 patients with pure DCIS, in 39 with DCIS adjacent to invasive carcinoma (IDC) and 63 patients with T1 IDC, using tissue microarrays and specific antibodies against MMPs and TIMPs. Immunohistochemical results were categorized using a specific software program. The data were analysed by unsupervised hierarchical cluster analysis by each cellular type. IDC showed a higher expression rate of MMP-7 and TIMP-1 than pure DCIS, as well as a higher expression rate of MMP-9 and TIMP-3 than the DCIS component of mixed cases, whereas pure DCIS showed a higher rate of expression of MMP-9 and -11 and TIMP-3 than in the DCIS component of mixed cases. Pure DCIS with a periductal inflammatory infiltrate showed significantly higher MMP-2, -14 and TIMP-1. Dendograms identified two cluster groups with distinct MMP/TIMP expression profiles in neoplastic cells and fibroblastic or mononuclear inflammatory cells surrounding the neoplastic ducts of pure DCIS. CONCLUSIONS: The results indicate the distinct variability in MMP/TIMP expression by DCIS, which may be of potential biological and clinical interest in breast cancer.
Assuntos
Neoplasias da Mama/enzimologia , Carcinoma Intraductal não Infiltrante/enzimologia , Metaloproteinases da Matriz/metabolismo , Inibidores Teciduais de Metaloproteinases/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Imuno-Histoquímica , Análise Serial de TecidosRESUMO
OBJECTIVES: Gene expression analysis has identified several breast cancer subtypes, including luminal, epidermal growth factor receptor-2 positive (HER2+), and basal-like. To determine if our proposed molecular taxonomy correlates with biological and clinical behavior. This is based on four biological markers: estrogen and progesterone receptors (ER and PR, respectively), HER2 and the epidermal growth factor receptor-1 (HER1), all of them being determined by quantitative assays. STUDY DESIGN: The biological parameters were examined by enzyme immunoassay, radioligand-binding assay or ELISA, in tumors from 787 patients with invasive breast cancer. Patients were prospectively evaluated over a median follow-up period of 50 months. Subtype definitions were as follows: luminal (ER+), HER2+ (HER2+, ER-, PgR-) and basal-like (HER2-, ER-, PgR-). In addition, we divided basal tumors into two groups based on their HER1 status. RESULTS: A 55.8% of tumors were of luminal type, 11.9% basal-like HER1+, 10.7 basal-like HER1-, and the remainder 21.6% HER2+. Both HER2+ and basal-like subtypes were more frequent in younger and premenopausal women, showing a higher percentage of cases of poorly differentiated tumors and higher S-phase fraction, when compared with those of luminal subtype. Multivariate analysis demonstrated that the subtype of tumor was related to both relapse and overall survival, being those of luminal subtype associated with the best prognosis. CONCLUSIONS: Through the classification of breast tumors in four groups, according to their ER, PgR, HER2 and HER1 status, it is possible to obtain a major division of breast tumors associated with significant differences in biological features and clinical behavior.
Assuntos
Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Receptor ErbB-2/genética , Neoplasias da Mama/genética , Receptores ErbB/genética , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Análise de SobrevidaRESUMO
An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinase (MMP)-1, -2, -7, -9, -11, -13 and -14, tissular inhibitors of metalloproteinase (TIMP)-1, -2 and -3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast were performed. To identify specific groups of tumours with distinct expression profiles the data were analysed by unsupervised hierarchical cluster analysis by each cellular type. We did not find well-defined cluster of cases for tumour cells or fibroblastic cells. However, for mononuclear inflammatory cells the dendogram shows a first-order division of the tumours into two distinct MMP/TIMP molecular profiles, designated group 1 (n=89) and group 2 (n=42). Matrix metalloproteinase-7, -9, -11, -13 and -14, and TIMP-1 and -2, were identified as showing significant high expression in group 2 compared with group 1. Multivariate analysis demonstrated that clustering for mononuclear inflammatory cells was the most potent independent factor associated with distant relapse-free survival (group 2: 5.6 (3.5-9.6), P<0.001). We identify a phenotype of mononuclear inflammatory cells infiltrating tumours, which is associated with the development of distant metastasis. Therefore, this finding suggests that these host inflammatory cells could be a possible target for inhibition of metastasis.
Assuntos
Neoplasias da Mama/enzimologia , Carcinoma Ductal/enzimologia , Carcinoma Ductal/secundário , Leucócitos Mononucleares/metabolismo , Metaloproteinases da Matriz/metabolismo , Recidiva Local de Neoplasia/metabolismo , Inibidores Teciduais de Metaloproteinases/metabolismo , Biomarcadores Tumorais/metabolismo , Western Blotting , Neoplasias da Mama/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Leucócitos Mononucleares/imunologia , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Taxa de Sobrevida , Análise Serial de Tecidos/métodosRESUMO
AIM: To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to assess their possible relationship to prognosis. METHODS: We performed an immunohistochemical study using tissue microarrays (containing more than 260 cancer specimens, from 31 HCC patients and controls) to determine the presence of specific antibodies against AR, ER, PgR and ApoD, correlating their findings with several clinico-pathological and biological variables. The staining results were categorized using a semi-quantitative score based on their intensity, and the percentage of immunostained cells was measured. RESULTS: A total of 21 liver tumors (67.7%) were positive for AR; 16 (51.6%) for ER; 26 (83.9%) for PgR and 12 (38.7%) stained for ApoD. We have found a wide variability in the immunostaining score values for each protein, with a median (range) of 11.5 (11.5-229.5) for AR; 11.1 (8.5-65) for ER; 14.2 (4-61) for PgR; and 37.7 (13.8-81.1) for ApoD. A history of heavy ethanol consumption, correlated positively with AR and PgR and negatively with ER status. HCV chronic infection also correlated positively with AR and PgR status. However, the presence of ApoD immunostaining did not correlate with any of these variables. Tumors with a positive immuno-staining for PgR showed a better prognosis. CONCLUSION: Our results indicate a moderate clinical value of the steroid receptor status in HCC, emphasizing the need to perform further studies in order to evaluate the possible role of new hormonal-based therapies.
Assuntos
Apolipoproteínas D/análise , Carcinoma Hepatocelular/química , Glicoproteínas/análise , Neoplasias Hepáticas/química , Fígado/química , Proteínas de Membrana Transportadoras/análise , Receptores Androgênicos/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS: To evaluate the expression of androgen receptors (AR) and two androgen-induced proteins [apolipoprotein D (ApoD) and pepsinogen C (PepC)] in ductal carcinoma in situ (DCIS) of the breast. METHODS AND RESULTS: AR, ApoD and PepC expression was examined in 28 cases of pure DCIS and in 31 cases of DCIS adjacent to invasive carcinoma of the breast using immunohistochemical methods and then correlated with the architectural subtype, the degree of differentiation and the ostrogen receptor (ER)/progesterone receptor (PgR)/HER-2 status. We found no significant differences between pure DCIS and DCIS adjacent to invasive breast cancer regarding the percentage of positive cases for ApoD (64.3% versus 54.8%), PepC (42.9% versus 48.4%), ER (64.3% versus 58.1%), PgR (60.7% versus 58.1%) and HER-2 (39.3% versus 67.7%). However, there was a significantly higher percentage of AR+ DCIS among those adjacent to invasive carcinomas of the breast than among pure DCIS lesions (93.5% versus 60.9%) (P = 0.009). AR expression did not correlate with architectural subtype, degree of differentiation, or ER/PgR/HER-2/ApoD/PepC status, in cases of pure DCIS, nor in DCIS adjacent to invasive carcinoma of the breast. CONCLUSIONS: AR expression may represent an independent predictive factor in DCIS of the breast.
Assuntos
Apolipoproteínas D/metabolismo , Neoplasias da Mama/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , Glicoproteínas/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Pepsinogênio C/metabolismo , Receptores Androgênicos/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinases (MMPs) 1, 2, 7, 9, 11, 13, 14, and their tisullar inhibitors (TIMPs) 1, 2, and 3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast (65 with and 66 without distant metastasis) and controls were performed. Staining results were categorised using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically. We observed a broad variation of the total immunostaining scores and the cell type expressing each protein. There were multiple and significant associations between the expression of the different MMPs and TIMPs evaluated and some parameters indicative of tumour aggressiveness, such as large tumour size, advanced tumour grade, high Nottinham prognostic index, negative oestrogen receptor status, peritumoural inflammation, desmoplastic reaction, and infiltrating tumoural edge. Likewise, the detection of elevated immunohistochemical scores for MMP-9, 11, TIMP-1, and TIMP-2, was significantly associated with a higher rate of distant metastases. The expression of MMP-9 or TIMP-2 by tumour cells, MMP-1, 7, 9, 11, 13, or TIMP-3 by fibroblastic cells, and MMP-7, 9, 11, 13, 14, TIMP-1, or TIMP-2 by mononuclear inflammatory cells, was also significantly associated with a higher rate of distant metastases.
Assuntos
Neoplasias da Mama/enzimologia , Carcinoma Ductal/enzimologia , Metaloproteinases da Matriz/metabolismo , Inibidores Teciduais de Metaloproteinases/metabolismo , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal/patologia , Feminino , Humanos , Imuno-Histoquímica , Isoenzimas/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise Serial de Tecidos/métodosRESUMO
Epidermal growth factor receptor (EGFR) is a membrane receptor expressed in a variety of solid human cancers and directly related with poor prognosis. The objective of this work was to evaluate the EGFR content in breast carcinomas, its possible relationship with different clinical-pathological parameters, and its potential prognostic significance and predictive value. EGFR levels were examined by radioligand binding assays in 846 patients with invasive breast cancer. The median follow-up period was 50 months. There was a wide variability of EGFR levels among the studied tumors (0.01-403 fmol/mg protein). Statistical analysis showed that EGFR levels were significantly higher in younger patients (p=0.0001). EGFR were also notably higher in ER-negative or PgR-negative tumors than in ER-positive (p=0.0001) or PgR-positive tumors (p=0.001). In addition, the presence of high intratumoral EGFR levels (cut-off: 6 fmol/mg protein) was associated with both shorter relapse-free survival (p=0.04) and overall survival (p=0.01) in the group of patients as a whole, as well as with overall survival in the subgroup of patients without any type of systemic adjuvant treatment (p=0.02). However, EGFR levels did not achieve significance as independent prognostic factor in the multivariate analysis. There is a wide variability of intratumoral EGFR levels in breast carcinomas, and these protein levels correlated positively with a poor prognosis in the t univariate analysis. However, further studies are necessary in order to assess the possible clinical value of EGFR in combination with other essential components of the EGFR family network.
Assuntos
Neoplasias da Mama/patologia , Receptores ErbB/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , DNA de Neoplasias/metabolismo , Feminino , Citometria de Fluxo , Humanos , Técnicas Imunoenzimáticas/métodos , Pessoa de Meia-Idade , Invasividade Neoplásica , Valor Preditivo dos Testes , Prognóstico , Ensaio Radioligante , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Análise de SobrevidaRESUMO
BACKGROUND: Cathepsin D is the proteolytic enzyme most frequently implicated as a prognostic factor in primary breast cancer. In the present study we evaluated by means of an immunoradiometric assay the tumor content of this protease in primary breast cancer, its relationship with tumor-related clinical and pathological parameters, and its prognostic significance in a large series of breast cancer patients. METHOD: The study comprised 1033 women with histologically established invasive breast cancer. Cathepsin D was measured in cytosol samples by means of an immunoradiometric assay to determine the total amount of cathepsin D (52 kDa, 48 kDa and 34 kDa). Evaluation of relapse-free survival and cause-specific survival was performed in the group of 1003 patients without evidence of metastasis at the time of initial diagnosis. The median follow-up of the patients who were free of recurrence was 54 months. RESULTS: Cathepsin D levels showed a wide range among the studied tumors (n = 1033; median (range) 41 (0.9-2504) pmol/mg protein). Statistical analysis showed that the median cathepsin D levels were considerably higher in large tumors (T2-4) than in smaller ones (T1) (p = 0.017), as well as in node-positive than in node-negative tumors (p = 0.004). Cathepsin D levels were also higher in ductal tumors than in the other histological types (p = 0.001), as well as in moderately or poorly differentiated tumors (p < 0.001). Likewise, the median value of the protease was significantly higher in ER or PgR-positive tumors than in hormone receptor-negative ones (p = 0.011 and p = 0.004, respectively), as well as in aneuploid tumors than in diploid tumors (p = 0.029). Multivariate analysis demonstrated that elevated cathepsin D levels (> 59 pmol/mg protein) were notably associated with a shorter cause-specific survival in the whole group of patients with breast cancer, as well as in the subgroup of node-positive patients (p < 0.05). CONCLUSIONS: This study suggests that elevated intratumoral cathepsin D levels may identify a subset of node-positive breast cancer patients showing a high probability of earlier death.
Assuntos
Neoplasias da Mama/enzimologia , Catepsina D/análise , Citosol/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Taxa de SobrevidaRESUMO
BACKGROUND: Matrix metalloproteases (MMPs), enzymes with the ability to degrade the extracellular matrix, play an important role in tissue invasion by cutaneous malignant melanoma (CMM). One specific MMP, collagenase-3 (MMP-13), is thought to have a key function in the activation of MMP. AIMS: To evaluate the expression of MMP-13 in CMM and assess its possible relationship to clinical and pathological parameters. METHODS: MMP-13 expression was analyzed in 51 paraffin-embedded tumor samples from patients with invasive CMM, ten samples from in situ melanomas, and in eight samples from benign lesions (three dermal melanocytic nevi, three compound melanocytic nevi and two atypical melanocytic nevi) using immunohistochemical techniques. The median follow-up period in patients with invasive CMM was 50 months. RESULTS: Benign lesions were consistently negative for MMP-13, whereas three of the ten in situ melanomas (30%) and 23 of the 51 invasive CMMs (45%) showed positive immunostaining for MMP-13. The percentage of MMP-13-positive tumors correlated significantly and positively with the mitotic index (p=0.002) in invasive CMM. However, our results did not show any significant association between tumoral MMP-13 expression and relapse-free survival in patients with invasive CMM. CONCLUSIONS: MMP-13 appears to be a factor associated with tumor aggressiveness in CMM. It seems to eliminate an important barrier not only against tumoral invasion but also against proliferation.
Assuntos
Colagenases/metabolismo , Regulação Neoplásica da Expressão Gênica , Melanoma/enzimologia , Neoplasias Cutâneas/enzimologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Intervalo Livre de Doença , Feminino , Regulação Enzimológica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Metaloproteinase 13 da Matriz , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Cathepsin D is the proteolytic enzyme most frequently implicated as a prognostic factor in primary breast cancer. In the present study we evaluated by means of an immunoradiometric assay the tumor content of this protease in primary breast cancer, its relationship with tumor-related clinical and pathological parameters, and its prognostic significance in a large series of breast cancer patients. METHOD: The study comprised 1033 women with histologically established invasive breast cancer. Cathepsin D was measured in cytosol samples by means of an immunoradiometric assay to determine the total amount of cathepsin D (52 kDa, 48 kDa and 34 kDa). Evaluation of relapse-free survival and cause-specific survival was performed in the group of 1003 patients without evidence of metastasis at the time of initial diagnosis. The median follow-up of the patients who were free of recurrence was 54 months. RESULTS: Cathepsin D levels showed a wide range among the studied tumors (n=1033; median (range) 41 (0.9-2504) pmol/mg protein). Statistical analysis showed that the median cathepsin D levels were considerably higher in large tumors (T2-4) than in smaller ones (T1) (p=0.017), as well as in node-positive than in node-negative tumors (p=0.004). Cathepsin D levels were also higher in ductal tumors than in the other histological types (p=0.001), as well as in moderately or poorly differentiated tumors (p<0.001). Likewise, the median value of the protease was significantly higher in ER or PgR-positive tumors than in hormone receptor-negative ones (p=0.011 and p=0.004, respectively), as well as in aneuploid tumors than in diploid tumors (p=0.029). Multivariate analysis demonstrated that elevated cathepsin D levels (>59 pmol/mg protein) were notably associated with a shorter cause-specific survival in the whole group of patients with breast cancer, as well as in the subgroup of node-positive patients (p<0.05). CONCLUSIONS: This study suggests that elevated intratumoral cathepsin D levels may identify a subset of node-positive breast cancer patients showing a high probability of earlier death. (Int J Biol Markers 2005; 20: 103-11).
RESUMO
BACKGROUND: Hyaluronan a high-molecular weight glycosaminoglycan, is considered to be involved in the growth and progression of malignant tumours. The objective of this work was to evaluate the cytosolic hyaluronan content in gastric cancer cells, its possible relationship with clinicopathological tumour parameters and its potential prognostic significance. METHODS: Cytosolic hyaluronan levels were examined utilizing immunoenzymatic techniques in 129 patients with gastric cancer. The mean follow-up period for these patients was 28 months. RESULTS: Cytosolic hyaluronan levels ranged widely in tumours as well as in adjacent mucosal samples (median (range) 2822 (50-24,523) versus 3650 (507-20,782) ng/mg protein). Statistical analysis showed that tumour hyaluronan levels correlated significantly with patient's sex and the presence of lymphatic invasion. In addition, high tumour hyaluronan levels were significantly associated with shorter overall survival period (p<0.05). CONCLUSIONS: Our results suggest that high tumoral cytosolic hyaluronan levels are associated with lesions of unfavorable outcome in gastric cancer patients. Thus, hyaluronan may provide additional prognostic information to that given by other biochemical markers currently used in gastric cancer.
Assuntos
Adenocarcinoma/classificação , Ácido Hialurônico/análise , Recidiva Local de Neoplasia , Neoplasias Gástricas/química , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Citosol/química , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Análise de SobrevidaRESUMO
BACKGROUND: The protein encoded by the c-erbB-2 gene is a membrane receptor expressed in a variety of solid human cancers and directly related to poor prognosis. The objective of this work was to evaluate the clinical value of the quantification of membranous oncoprotein levels in gastric cancer. MATERIALS AND METHODS: Membranous c-erbB-2 levels were examined by means of a sandwich immunoenzymatic assay in 82 patients with gastric cancer. The median follow-up period for these patients was 16 months. In addition, c-erbB-2 expression was analyzed by immunohistochemistry in 57 gastric carcinomas. RESULTS: Membranous c-erbB-2 levels ranged widely in the studied tumors (44-112,000 NHU/mg protein). Median c-erbB2 content was significantly higher in intestinal-type tumors than in diffuse-type tumors (p = 0.01). In addition, high levels of c-erbB-2 were significantly associated with shorter relapse-free survival and overall survival in patients with resectable gastric carcinomas (p = 0.01 and p = 0.04, respectively). However, the correlation between immunohistochemistry and ELISA determinations did not reach statistical significance. CONCLUSION: Our results suggest a potential prognostic value of membranous c-erbB-2 quantification by immunoenzymatic assay in gastric cancer. However, its possible role in the selection of patients with a view to the possible introduction of Herceptin as a novel drug against gastric cancer is at present uncertain.
Assuntos
Membrana Celular/metabolismo , Receptor ErbB-2/biossíntese , Neoplasias Gástricas/metabolismo , Idoso , Intervalo Livre de Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoensaio , Imuno-Histoquímica , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Fatores de TempoRESUMO
BACKGROUND: Epidermal growth factor receptor (EGFR) and c-erbB-2 are membrane receptors expressed in a variety of solid human cancers and directly correlated with poor prognosis. The objective of this work was to evaluate the EGFR and c-erbB-2 levels in non-resectable gastric carcinomas, their possible relationship with a variety of clinicopathological tumor parameters, and their prognostic significance. METHODS: This was a prospective analysis of 65 patients with unresectable gastric carcinomas (UICC R1 or R2), who underwent palliative surgery and were followed up for a median period of 13 months. Membranous EGFR levels were examined by radioligand binding assays and cytosolic c-erbB-2 levels by means of an immunoenzymatic assay. RESULTS: There was a wide variability in EGFR (80.3-2910 fmol/mg of protein) and c-erbB-2 (0.4-10071 NHU/mg of protein) levels in neoplastic tissues from patients with unresectable gastric carcinomas. Median c-erbB2 was significantly higher in tumors of the intestinal type than in tumors of the diffuse type (p = 0.035) and in R2 than in R1 tumors (p = 0.016). Statistical analysis showed that there was no relationship between tumor c-erbB-2 or EGFR content and any other patient or tumor characteristics. However, high levels of EGFR were significantly associated with a shorter overall survival (p = 0.01). CONCLUSION: Our data suggest a role of both transmembrane proteins in the progression of gastric cancer. EGFR and c-erbB-2 contents in unresectable gastric cancer could be utilized as appropriate biological markers for selecting candidates for treatment based on EGFR and/or c-erbB-2 inhibition.
Assuntos
Biomarcadores Tumorais , Receptores ErbB/biossíntese , Receptor ErbB-2/biossíntese , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/metabolismo , Carcinoma/mortalidade , Citosol/metabolismo , Feminino , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Ensaio Radioligante , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Fatores de TempoRESUMO
BACKGROUND: The Trefoil Factor 1 (TFF1/pS2), a peptide consisting of 60 amino acids, is the most abundant estrogen-induced messenger RNA in MCF-7 breast cancer cells and is also expressed by colorectal carcinomas. The objective of this work was to evaluate the cytosolic TFF1 content in colorectal carcinomas, its possible relationship with estrogen and progesterone receptors as well as with clinicopathological tumor parameters, and its potential prognostic significance. METHODS: Cytosolic TFF1 levels were examined by immunoradiometric assay in 178 patients with resectable colorectal cancer. The mean follow-up period was 32 months. RESULTS: There was a wide variability of cytosolic TFF1 levels in tumor-surrounding mucosa samples (0.09-42.5 ng/mg protein) as well as in tumors (0.01-270 ng/mg protein). Comparison of paired mucosa and carcinoma samples showed significantly higher TFF1 levels in tumors (mean: 17.1 ng/mg protein) than in mucosa samples (10 ng/mg protein) (p = 0.027). TFF1 levels were significantly higher in mucosa samples surrounding distal colon and rectal tumors (p = 0.0001) and in tumor samples obtained from older patients (p = 0.007). However, there were no significant differences in tumor TFF1 levels with respect to clinicopathological parameters such as the patient's sex, tumor location, stage, histological grade, ploidy, S-phase, or tumor estrogen and progesterone receptors. In addition, there was no significant relationship between tumor TFF1 levels and disease outcome. CONCLUSIONS: TFF1 may play an as yet undetermined role in the tumorigenesis of colorectal carcinomas. However, cytosolic levels of TFF1 do not seem to have any prognostic significance in colorectal carcinomas.
Assuntos
Neoplasias Colorretais/patologia , Proteínas/genética , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Criança , Pré-Escolar , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Citosol/metabolismo , Intervalo Livre de Doença , Seguimentos , Humanos , Mucosa Intestinal/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Análise de Sobrevida , Fatores de Tempo , Fator Trefoil-1 , Proteínas Supressoras de TumorRESUMO
PURPOSE: The purpose of this study was to evaluate the role of three-dimensional spiral computed tomographic angiography (SCTA) for the assessment of the feasibility and results of endoluminal repair of infrarenal abdominal aortic aneurysm. METHODS: Laboratory studies: Phantom glass aneurysms, filled with contrast, underwent SCTA. The correlation between SCTA and laboratory measurements of linear dimensions and volumes was highly accurate (r(2) = 1.0). CLINICAL STUDIES: From the first 7 patients that were suitable for endoluminal repair, the correlation between SCTA and angiocatheter measurements was 0.85 to 0.99 (P <.04), but there was poor agreement between individual values. As determined from the measurements by 2 experienced investigators, intraobserver and interobserver errors for volume calculation in 12 randomly chosen scans from a total of 120 scans were 5.7 and 4.4 mL, respectively (range of volumes, 100-403 mL). The conditions of 53 patients were judged suitable for endoluminal repair of which 30 patients reached 1 year or more follow-up. The median aneurysm neck length and diameter were 24.5 mm (range, 11.5-60.8 mm) and 23.4 mm (18.3-31.5 mm), respectively. The fate of the sac after endografting by two techniques (pre-expanded polytetrafluoroethylene [PTFE] fixed with Palmaz stents and endografts) was defined with three-dimensional SCTA. RESULTS: The sac volume after endografting by pre-expanded PTFE (n = 12 patients) showed a significant median increase (P =.02) from 129 mL before surgery to 141 mL at 5 days after the operation with no change at 6 (139 mL), 12 (137 mL), and 18 (159 mL) months later. With the endografts (n = 18), there was an initial increase in median volume at 5 days (179-194 mL; P =.02) and then a significant shrinkage at 6 (148 mL; P =.012) and 12 (94.9 mL; P =.02) months. CONCLUSION: Three-dimensional SCTA has been validated and is both precise and reliable. Interobserver and intraobserver errors are within acceptable ranges. Angiocatheter measurements are less accurate and may give misleading information when used for patient selection and endograft construction. The sac volume increased after endografting and later shrank in patients who were treated with endografts, but not in those patients treated with pre-expanded PTFE. We propose that three-dimensional SCTA should be regarded as the gold standard for linear and volumetric measurement for infrarenal abdominal aortic aneurysm.