No abstract

E-cadherin (E-cad) plays a major role in the maintenance of cell-cell adhesion in epithelial tissues, and impaired E-cad expression correlates with tumour invasion and metastasis. Alpha-catenin (alpha-cat), an undercoat protein of adherens junctions, binds to the cytoplasmic domain of E-cad and is essential for linking E-cad to actin-based cytoskeleton. We investigated E-cad and alpha-cat expression in 60 human gastric cancers immunohistochemically. The 60 gastric cancers were classified into 18 (30%) in which alpha-cat expression was preserved, and 42 (70%) reduced cases. The reduction of alpha-cat expression was significantly related to dedifferentiation, depth of invasion, infiltrative growth and lymph node metastasis. We also examined the co-expression of alpha-cat and E-cad. Seventeen (28%) tumours preserved both molecules [alpha-cat(+)/E-cad(+)] and 33 (55%) tumours reduced both [alpha-cat(-)/E-cad(-)], whereas 9 (15%) tumours exhibited alpha-cat(-)/E-cad(+). The frequency of lymph node metastasis in alpha-cat(-)/E-cad(+) tumour (67%) was significantly higher than that in alpha-cat(+)/E-cad(+) tumours (24%) and was close to that in alpha-cat(-)/E-cad(-) tumours (82%). The frequency of haematogenous liver metastasis in alpha-cat(-)/E-cad(+) tumours (44%) was significantly higher than that in alpha-cat(+)/E-cad(+) tumours (6%) or alpha-cat(-)/E-cad(-) tumours (9%). Thus, in all E-cad(+) tumours, the frequency of lymph node and liver metastasis was higher in alpha-cat(-) tumours than in alpha-cat(+) tumours. alpha-Cat expression is apparently better at predicting tumour invasion and metastasis than E-cad expression.

Generally, LN metastases are seen in a small percentage of patients with early gastric cancer with mucosal or submucosal invasion [7]. In recent years, the technique of laparoscopy-assisted distal gastrectomy (LADG) with regional LN dissection has been developed and employed for early gastric cancer [8]. In March, 1997, we began to perform LADG as a minimally invasive surgery for early gastric cancer. However, the feasibility of LADG for early gastric cancer and the associated clinical outcome of patients who undergo LADG for early gastric cancer remain unclear.We therefore conducted a review of patients who underwent LADG for early gastric cancer, in an effort to compare the operative times, intra-operative blood loss, number of removed lymph nodes, postoperative recovery, and morbidity and mortality rates of LADG and conventional open distal gastrectomy (ODG). Our research was aimed at determining whether the laparoscopic procedure of LADG for early gastric cancer is really safe and minimally invasive, and whether or not the LADG improves quality of life, compared with ODG. Patients and methods PatientsThe patients were preoperatively diagnosed as having an early gastric cancer located in the lower or middle third of the stomach, from the results of endoscopy, endoscopic ultrasonography (EUS), and examination of biopsy specimens. The indications for LADG were that: (1) the tumor was located in the middle or lower part of the stomach, (2) the invasion of the tumor was limited to the mucosal layer or the submucosal layers (SM1). Results. The clinical and pathological backgrounds of the patients in the two groups were similar. The duration of surgery was not significantly different between the two groups, but the blood loss in the LADG group was significantly less than that in the ODG group. The number of removed lymph nodes was not significantly different between the two groups. The times to the first passing of flatus, first walking, and the restarting of oral intake; the length of hospital stay; and the duration of epidural analgesia were significantly shorter in the LADG group. The morbidity rate in the LADG group was lower than that in the ODG group. Conclusions. LADG is a safe and minimally invasive surgical technique, after which we can expect a faster recovery.

SummanrEpidermal growth factor (EGF) mediates many pleiotrophic biological effects, one of which is alteration of cellular morphology. In the present study. we examine the possibility that this alteration in cell morphology is caused in part by the dysfunction of cadherin-mediated cell-cell adhesion using the human oesophageal cancer cell line TE-2R. which expresses E-cadherin and EGF receptor. In the presence of EGF. TE-2R changed its shape from round to fibroblastic and its colony formation from compact to sparse. Vanadate. a tyrosine phosphatase inhibitor, further potentiated the EGF response. whereas herbimycin A. a tvrosine kinase inhibitor, interfered with it. Moreover. EGF enabled the cells to invade in organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its localisation from the lateral adhesion site to the whole cell surface. Both a-and P-catenin.cadherin-binding proteins, were also expressed at the same level throughout these morphological changes.Finally. we examined tyrosine phosphorylation of E-cadherin and a-and P-catenin. and observed tyrosine phosphorylation of -catenin induced by EGF. These results suggest that EGF counteracts E-cadherinmediated junctional assembly through phosphorylation of P-catenin and modulates tumour cell behaviour to a more aggressive phenotype.

Reduced expression of E-cadherin is associated with tumour invasiveness and metastasis. To elucidate whether E-cadherin expression correlates with clinical outcome in patients with oesophageal cancer, 62 patients were investigated immunohistochemically using an anti-E-cadherin monoclonal antibody (HECD-1). Eight patients had normal levels of expression in the tumour, 25 had tumours that expressed high levels (50 per cent or more tumour cells staining positive for E-cadherin) and 29 had tumours expressing low levels (less than 50 per cent of cells expressing E-cadherin). Patients with normally expressing tumours had a better prognosis at 3 years than those with low-expressing tumours (P < 0.05). Postoperative death was correlated significantly with lymphatic invasion, lymph node metastasis, E-cadherin expression and depth of invasion (P < 0.05). Furthermore, haematogenous recurrence was correlated with E-cadherin expression (rs = 0.38, P < 0.01) and blood vessel invasion (rs = 0.28, P < 0.05). These results suggest that evaluation of E-cadherin immunoreactivity may predict haematogenous recurrence and poor prognosis in patients with oesophageal cancer.