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Aims: To study the expression and prognostic significance of the cell adhesion molecule E-cadherin in oesophageal tumours from the UK (low risk area) and China (high risk area)., Methods: E-cadherin expression was measured immunohistochemically in resected tumours from 17 patients in the UK with adenocarcinoma, 23 patients from the UK with squamous carcinoma, and 30 patients from China with squamous carcinomas who survived for five years postoperatively and compared with similar tumours from patients in the same regions who did not survive (140 tumours in all)., Results: Normal squamous epithelial cells and well differentiated areas of tumours showed membranous staining for E-cadherin expression. Cytoplasmic staining, heterogeneous staining, or an absence of staining was seen in dysplastic epithelium and in less well differentiated areas of tumours. Only one of 140 primary tumours had homogeneous membranous expression. In tumours from UK patients with adenocarcinoma (p = 1.00) and from Chinese patients with squamous carcinomas (p = 0.06) there was no correlation between E-cadherin absence and non-survival. In tumours from UK patients with squamous carcinomas there was a significant correlation between absence of E-cadherin and non-survival (p = 0.009). Tumours from UK patients with squamous carcinoma who survived were significantly less likely to be E-cadherin absent than those from Chinese patients with squamous carcinomas who survived (p = 0.007). Multivariate analysis (n = 37 UK, paired data) showed that absence of E-cadherin in the primary tumour was a weak independent prognostic factor for non-survival (30% significance level; p = 0.26; odds ratio = 3.56). In UK nodal metastases there was no correlation between E-cadherin expression and survival., Conclusions: Squamous carcinomas from UK patients differed from both adenocarcinomas from UK patients and carcinomas from Chinese patients with respect to E-cadherin expression and prognostic significance. In tumours from UK patients, E-cadherin absence in the primary carcinoma (a weak independent prognostic factor) but not metastases correlated with non-survival.

Tumour heterogeneity may pose a problem when biopsy specimens are taken to measure proliferation (for example, in assessing response to therapy). Two "biopsy specimens" were taken from the centre and two from the edge of the luminal surface of 20 resected oesophageal adenocarcinomas. The proliferation index for each "biopsy specimen" was measured by counting Ki67 labelled nuclei in histological sections. The proliferation index was not associated with tumour differentiation or stage. There was site specific heterogeneity with a significant difference in proliferation index between the central (mean (SD) 36.4 (9.7)) and edge "biopsy specimens" (39.3 (9.9)). There was, however, a wide range of differences between pairs of "biopsy specimens" from both sites. In conclusion, if a tumour is to be sampled for measurement of the proliferation index before and after treatment, then the sequential biopsy specimens (preferably duplicated on each occasion) should be taken consistently from a leading edge of the lesion.

The multidrug resistance gene product P-glycoprotein (P-GP) was assessed immunohistochemically (by antibody JSB-1) in biopsy specimens from 27 oesophageal squamous carcinomas and 10 adenocarcinomas before treatment with mitomycin, ifosfamide and cisplatin (MIC). Tumours were assessed following treatment and correlation with response sought. Of the squamous carcinomas, 74% (20/27) responded to MIC but only one expressed P-GP before and after treatment. Of the adenocarcinomas, 30% (three of 10) responded. Seven of the 10 adenocarcinomas expressed P-GP before treatment but all 10 were P-GP positive after chemotherapy. The difference in prevalence and induction of P-GP between the histological types was highly significant and may correlate with the greater response to MIC seen in squamous carcinomas compared with adenocarcinomas. P-GP cannot be used as a predictive marker of response as tumours express it inconsistently with response to MIC. Resistance to MIC may be due to other mechanisms.