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Summary In the present study we

A seris of coorta carcinomas (n = 49) resected from patients with known chinical outcomes were analysed for E-caderin expression using in situ hybridisation to measure mRNA. Patients surviving 5 years or longer (n = 31) exhibited significantly higher kvels of E-cadherin mRNA than those surviving less than 5 years (n = 18, P = 0.003). These peiminary reslts from this small sample suggest that E-cadherin expression may be a useful prognostic marker in colorectal cancer patients.Keywords: colorectal carcinomas; E-cadherin; prognosis Colorectal cancer is one of the most common malignances in the developed world and remains a major publc health problem (King's Fund Forum, 1990). Pathological staging, using the Dukes claation, offers an accurate guide to the outcome of patients who have undergone surgicl resection (Deans et al., 1992(Deans et al., , 1993 (Frixen et al., 1991). A large number of fresh human cancers also have been analysed for E-cadherin expression by immunohistochemistry (Takeichi, 1993), including clinical material denved from patients with colorectal cancer (Dorudi et al., 1993;Kinsella et al., 1993;Nigam et al., 1993).Generally, these investigations have revealed an inverse relationship between E-cadherin expression and tumour grade, with poorly differentiated tumours exhibiting reduced or absent immunoreactivity (Takeichi, 1993). Although downregulation of E-cadherin has been observed in undifferentiated (Dorudi et al., 1993;Kinsella et al., 1993;Nigam et al., 1993) and advanced colorectal carcinomas (Dorudi et al., 1993), no study has yet examined the possible relationship between expression of this cell adhesion molecule and prognosis in colorectal cancer. Such a relationship, however, has been exaied in three other tumour types: bladder, head and neck and gastric cancer (Brnguier et al., 1993; Mattijsen et al., 1993;Mayer et al., 1993). Uniformly, these authors all reported that a reduced level of E-cadherin was correlated significntly with poor prognosis, but the studies all used frozen material for E-cadherin immunohistochemistry, tended not to have stage-matched material and had lmited follow-up data (of less than 5 years) (Bringuier et al., 1993; Mattijsen et al., 1993;Mayer et al., 1993).Previously we showed that in colorectal cancer there is a good correlation between the presence of E-cadherin mRNA and protein (Dorudi et al., 1993

Summary The effects of acute hypoxia on integrin expression and adhesion to extracellular matrix proteins were investigated in two human melanoma cell lines, HMB-2 and DX3, and a human adenocarcinoma cell line, HT29. Exposure to hypoxia caused a significant downregulation of cell surface integrins and an associated decrease in cell adhesion. Loss of cell adhesion and integrin expression were transient and levels returned to normal within 24 h of reoxygenation. Other cell adhesion molecules, such as CD44 and N-CAM, were also downregulated after exposure of cells to hypoxia. Acute exposure to hypoxia of cells at confluence caused rapid cell detachment. Cell detachment preceded loss of viability. Detached HMB-2 and DX3 cells completely recovered upon reoxygenation, and floating cells re-attached and continued to grow irrespective of whether they were left in the original glass dishes or transferred to new culture vessels, while detached HT29 cells partly recovered upon reoxygenation. Cell detachment after decreased adhesion appears to be a stress response, which may be a factor enabling malignant cells to escape hypoxia in vivo, with the potential to form new foci of tumour growth.

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