RESUMO
AIMS: Metaplastic changes secondary to chronic inflammation at the gastro-oesophageal junction and at the pyloric antrum are recognized as the premalignant conditions of Barrett's oesophageal adenocarcinoma and intestinal-type gastric carcinoma (GC), respectively. Heparanase (HPSE) and cyclooxygenase (COX)-2 have been proved to play critical roles in inflammation as well as in cancer. The aim was to examine the meaning of their expression in inflammation-related carcinogenesis. METHODS AND RESULTS: First, expression of HPSE and COX-2 in 78 clinical tissues of Barrett's oesophagus was examined by immunohistochemistry and in situ hybridization. Their expression was increased during the metaplasia-dysplasia sequence with increased neovascularization. Successively, their expression in Barrett's dysplasia was compared with that of GC (22 cases of diffuse-type and 10 of intestinal-type). Interestingly, the expression pattern in Barrett's dysplasia was similar to that in intestinal-type GC, which mainly arises from chronic inflammation. Furthermore, cultured cell lines isolated from differentiated GC tissues, which are often found to be of intestinal-type, revealed up-regulated mRNA expression of HPSE and COX-2. CONCLUSIONS: HPSE and COX-2 are preferentially up-regulated in Barrett's oesophagus and intestinal-type GC. These molecules may play an important role during the development of inflammation-related adenocarcinoma of the upper gastrointestinal tract.
Assuntos
Adenocarcinoma/enzimologia , Esôfago de Barrett/enzimologia , Ciclo-Oxigenase 2/metabolismo , Neoplasias Esofágicas/enzimologia , Glucuronidase/metabolismo , Neoplasias Gástricas/enzimologia , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/genética , Adenocarcinoma/patologia , Esôfago de Barrett/genética , Esôfago de Barrett/patologia , Sequência de Bases , Carcinoma in Situ/enzimologia , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/genética , Primers do DNA/genética , Neoplasias Esofágicas/irrigação sanguínea , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Glucuronidase/genética , Humanos , Microvasos/patologia , Neovascularização Patológica , RNA Mensageiro/genética , RNA Neoplásico/genética , Neoplasias Gástricas/patologia , Regulação para CimaRESUMO
Signet-ring cell carcinoma (SRC) of the stomach exhibits diffuse growth and invasion without forming ducts. Destruction of the surrounding basal membrane and angiogenesis appear to be required for SRC to exhibit marked invasion and growth. We recently reported that heparanase (HPA) and cyclooxygenase-2 (COX-2) were strongly correlated with microvessel density, and that COX-2 expression is up-regulated by HPA in esophageal cancer. In this study, we examined the relationship between HPA expression and that of COX-2 in SRC of the stomach. We examined HPA and COX-2 expression in 3 cell lines derived from SRC of the stomach and in 50 SRC lesions of stomach by immunohistochemistry (IHC), in situ hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR). We also examined the relationships among HPA expression, COX-2 expression, and the clinicopathologic features of SRC, mean age, sex, invasion depth, regional lymph node metastasis, lymphatic invasion, and venous blood vessel invasion. Of the 3 cell lines, 2 exhibited both HPA and COX-2 mRNA expression on RT-PCR. Of the 3 cell lines, 1 exhibited only HPA mRNA expression on RT-PCR. Heparanase expression was confirmed in 23 (46%) of 50 tumor samples by IHC. COX-2 expression was confirmed in 25 (50%) of the 50 tumor samples by IHC. In situ hybridization revealed messenger RNA expression in the same area as in that revealed by IHC. A close correlation was noted between HPA and COX-2 expressions (P < .0001). The present study thus elucidated the biologic features of SRC of the stomach related to growth and angiogenesis.