RESUMO
Angiopoietins are endothelial growth factors, which play crucial roles in normal vascular development and tumor angiogenesis. We examined the expression profiles of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and Tie-2, a receptor for Ang-1 and Ang-2, in both colorectal adenocarcinoma and adjacent normal tissues, as judged by histology, in order to elucidate their relationships with microvascular density (MVD) and clinicopathologic properties. Higher MVD was associated with a lower degree of differentiation of colorectal adenocarcinoma. Immunohistochemical analysis revealed that the expression of Ang-2 and VEGF was significantly increased in colorectal adenocarcinoma compared to adjacent normal tissues (p < 0.01), and the expression of Ang-2 positively correlated with that of VEGF (r = 0.997, p < 0.01). In contrast, the expression of Ang-1 was lower in adenocarcinoma tissues than in adjacent normal tissues (p < 0.01), while there was no significant difference in Tie-2 expression in both tissues. Moreover, MVD was increased in Ang-2- and VEGF-expressing adenocarcinoma tissues compared to the Ang-2- and VEGF-negative tissues, respectively (p < 0.01). Importantly, MVD was lower in Ang-1-expressing adenocarcinoma tissues relative to Ang-1-negative tissues (p < 0.01). Furthermore, expression of Ang-2 as well as VEGF was significantly up-regulated in colorectal adenocarcinoma with diameters > or = 5 cm or with lymph-node metastases (p < 0.01). In conclusion, the increased expression of Ang-2 and the decreased expression of Ang-1 may be responsible for blood vessel formation and rapid growth of the colorectal adenocarcinoma.
Assuntos
Adenocarcinoma/irrigação sanguínea , Angiopoietina-2/metabolismo , Neoplasias Colorretais/irrigação sanguínea , Neovascularização Patológica/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Angiopoietina-1/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Microcirculação/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor TIE-2/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND & OBJECTIVE: Recent studies revealed a possible close association between the expression of some members of tumor-specific antigen MAGE (melanoma antigen) family and actively proliferated infantile cells. But the correlation of MAGE-A1 expression with proliferation of tumor cells and immune response at host local site has not been reported to date. Our study was to investigate the expression of MAGE-A1 in non-small cell lung carcinoma (NSCLC), and its relationship with Ki-67 expression, tumor-infiltrating lymphocyte (TIL) response, histologic grade, and pathological type. METHODS: Thirty NSCLC samples in formalin-fixed, paraffin-embedded sections were examined for MAGE-A1, Ki-67 and TIL response using SP immunohistochemical technique. RESULTS: The positive expression rate of MAGE-A1 was 80.00%(24/30) with high expression rate of 58.33%(14/24) and low expression rate of 41.67%(10/24). The positive expression rate of Ki-67 was 93.33%(28/30) with high expression rate of 57.14%(16/28) and low expression rate of 42.86% (12/28). TIL response was observed in 22 patients. There was a significant relationship between MAGE-A1 positive expression and Ki-67 positive expression (rs=0.578, P< 0.005), as well as between MAGE-A1 positive expression and TIL response (rs=0.505, P< 0.005). However, MAGE-A1 expression was not significantly correlated with histologic grade and pathological type (P >0.05). CONCLUSION: The NSCLC cells with MAGE-A1 positive expression possess high proliferation activity; meanwhile, the up-regulation of MAGE-A1 indicates the increase of antigen in tumor cells and the increase of local TIL response, indicating that MAGE-A1 may have potential to be used as a target for immunotherapy in NSCLC patient.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Antígeno Ki-67/análise , Neoplasias Pulmonares/imunologia , Linfócitos do Interstício Tumoral/imunologia , Proteínas de Neoplasias/análise , Adulto , Idoso , Antígenos de Neoplasias , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Antígenos Específicos de Melanoma , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
BACKGROUND & OBJECTIVE: Abnormality of FHIT gene has been proved to be frequent in certain malignant tumors closely related to environmental oncogenic factors, such as lung cancer. Foreign scholars have begun to explore the relationship between FHIT gene and other tumor suppressor genes, which are implicated in the pathogenesis of lung cancer. This study was designed to investigate the relationship between hMSH(2) and FHIT protein expression and to explore the correlation of hMSH(2) and FHIT protein expression with clinicopathologic features of lung cancer. METHODS: Immunohistochemical analysis of hMSH(2) and FHIT protein expression in 40 lung cancer cases and 15 adjacent non-cancer lung tissues was performed; the positive rates of FHIT and hMSH(2) proteins were measured by image analysis system. RESULTS: (1)The positive rates of FHIT and hMSH(2) proteins were 58.2% and 45.8% respectively in lung cancer tissues compared with 89.1% and 65.3% in non-cancer lung tissues. The expression levels of FHIT and hMSH(2) proteins were significantly lower in lung cancer tissues than that in non-cancer lung tissues (P< 0.01). (2)Reduced expression levels of both proteins were significantly related to tumor histology. The positive rate of the FHIT protein was 52.2% in squamous cell carcinoma compared with 63.4% in adenocarcinomas(P< 0.01), whereas the positive rate of the hMSH(2) protein was 35.6% in adenocarcinomas compared with 53.2% in squamous cell carcinoma(P< 0.01). (3)A correlation between FHIT reduced expression and lymph node metastasis was observed(P< 0.01). The positive rate of the FHIT protein was 54.1% in lung cancer tissues with metastasis compared with 60.5% in lung cancer tissues without metastasis. No association was found between hMSH(2) reduced expression and nodal metastasis(P >0.05). (4)Loss of FHIT protein correlated significantly with lasting and heavy smoking(P< 0.01). The positive rate of the FHIT protein was 53.1% in smoking group compared with 66.1% in non-smoking group. The reduction of hMSH(2) expression was not associated with smoking(P >0.05). (5)An inverse correlation was found between hMSH(2) reduced expression and FHIT protein loss (P< 0.01, RR=-0.54). CONCLUSION: FHIT gene may be a negative regulatory gene of hMSH(2) gene, and play an important role in the inactivation mechanism of hMSH(2) gene.
Assuntos
Hidrolases Anidrido Ácido , Carcinoma Pulmonar de Células não Pequenas/química , Proteínas de Ligação a DNA , Neoplasias Pulmonares/química , Proteínas de Neoplasias/análise , Proteínas Proto-Oncogênicas/análise , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Proteína 2 Homóloga a MutS , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas/genética , Fumar/metabolismoRESUMO
BACKGROUND & OBJECTIVE: There is evidence that cyclooxygenase-2(COX-2) involved in the occurrence and development of neoplasms. Elevated expression of COX-2 in carcinomas and antitumor effects of nonsteroidal antiinflammatory drug(COX-2 inhibitors) have been reported, but COX-2 expression in precancerous lesions and its association with angiogenesis is not clearly defined. The aim of this study was to investigate the expression of COX-2 protein and its association with microvessel density (MVD) during the experimental rat lung carcinogenesis. METHODS: Eighty Wistar rats were intra-leftlobar-bronchial instilled with 3-methylcholanthrene and diethylinitrosamine to induce lung squamous cell carcinoma, and ten rats were instilled lipiodol as control group. To acquire every pathological phase during the carcinogenesis, rats were sacrificed at intervals from fifteen days to nine months. COX-2 expression and MVD count in the samples of every pathological phase during the carcinogenesis were examined by immunohistochemistry. The immunohistochemical score of COX-2 was calculated by combining an estimate of the percentage of immunoreactive cells with an estimate of the staining intensity. Inter tumor MVD was marked by anti-Von Willebrand factor monoantibody. RESULTS: One hundred and forty seven specimens of every pathological phase during the carcinogenesis were obtained which including fourteen hyperplasia, twenty five squamous metaplasia, thirty three dysplasia, twelve carcinoma in situ, fifty four infiltration carcinoma, nine metastasis. The expression of COX-2 and MVD count increased during rat lung carcinogenesis. COX-2 immunohistochemical score was significantly higher in dysplasia, carcinoma in situ and metastasis(P < 0.01, P < 0.05, P < 0.05 respectively), and significant increased MVD were found in carcinoma in situ, infiltration carcinoma and metastasis (P < 0.01). During carcinogenesis, there was a significant correlation between COX-2 expression and MVD(r = 0.9521, P < 0.001, b = 11.51). CONCLUSION: COX-2 may play an important role during the carcinogenesis in experimental rat lung squamous cell carcinoma as well as its metastasis, partly by stimulating angiogenesis.