Summary Preoperative staging of gastric cancer is difficult. Several molecular markers associated with initiation and progression of cancer seem promising for obtaining preoperative prognostic information. To investigate whether these markers are indicative especially for the presence of lymph node metastases in patients with gastric cancer, we have examined primary tumour specimens from 105 patients with primary adenocarcinoma of the stomach entered in a surgical trial. In this trial, lymph node status was determined by strictly quality-controlled lymph node dissection and examination. The selected markers were growth regulators (p53, Rb and myc), metastasis-suppressor gene product (nm23), adhesion molecules (Ep-CAM, E-cadherin, CD44v5 and CD44v6) and urokinase-type plasminogen activator (u-PA). Also, the amount of eosinophilic and lymphocytic infiltrates available post-operatively was analysed with respect to its prognostic value for lymph node status. Moreover, the association of these parameters with survival and disease-free period (DFP) was evaluated. Of all molecular markers investigated, only Rb expression had a significant association with the presence of lymph node metastasis in both univariate and multivariate analysis. For curative resectability, a significant association was found with Rb and E-cadherin expression, while in multivariate analysis Rb and myc were selected as the combination with additional independent prognostic value, and E-cadherin had no additional independent value. For overall survival in univariate analysis, the amount of both eosinophilic and lymphocytic infiltrates and Rb and myc expression were of significant prognostic value. Only the amount of lymphocytic infiltrate had a prognostic significance for DFP. In stepwise multivariate analysis, TNM stage (I+II) and marked lymphocytic infiltrate were associated with better overall survival and longer DFP. We conclude that, if these results are confirmed in a larger series of patients, molecular markers can provide useful prognostic information.Keywords: gastric cancer; metastasis; prognosis; molecular marker Despite declining incidence, gastric cancer remains a major clinical management problem with poor prognosis: overall 5 year survival rates vary between 5% and 11%. Only a curative resection (complete tumour removal) offers hope of a cure, but the majority of the patients are diagnosed at an advanced disease stage (Allum et al., 1989). At diagnosis, the first decision to be made is whether or not to attempt a curative resection. This decision is based on stage of disease, which is assessed by radiograph of the stomach, chest and ultrasound of the liver or computerised tomography (CT) scan of the abdomen. Palliative resections offer no survival advantage and are associated with higher operative mortality rates compared with curative resections (Allum et al., 1989;Akoh et al., 1991; Wanebo et al., 1993). Laparoscopy and cytological examination of abdominal washings increase the accuracy of preoperative staging, but are not used r...

We compare the clinicopathological features of 98 Crohn's disease (CD) patients with initial symptoms at 40 years of age or older (elderly; male n = 56, female n = 42) with those of 347 CD patients with onset of symptoms between the age of 16 and 40 years (young adults; male n = 166, female n = 181). The frequency of presenting symptoms, such as diarrhea, rectal blood loss, and weight loss were comparable in both groups, except for abdominal pain/cramps, which occurred somewhat less frequently in the elderly (59% vs. 71%, p < 0.05). The mean lag time between onset of symptoms and first visit to a general practitioner (GP) was considerably shorter in the elderly than in the young adults (0.2 years vs. 0.6 years, p < 0.001), as was the lag time between GP and referral to a specialist (0.6 years vs. 1.0 years, p < 0.07). Overall, this resulted in a significantly (p < 0.01) shorter time to establish the diagnosis in the elderly (1.8 years vs. 2.7 years). Crohn's disease as correct initial diagnosis was in the elderly less frequently observed than in the young adults (49% vs. 61%, p < 0.05), in contrast to diverticulitis (7.1% vs. 0%) and malignancy (6.1% vs. 0.9%), which were more frequently encountered as incorrect preliminary diagnosis in the elderly (both p < 0.005). The percentage of patients who underwent an abdominal operation was similar in both groups (83% vs. 77%), but the diagnosis CD was in the elderly more frequently established at first operation than in young adults (25% and 12%, p < 0.005). The elderly were found to undergo a bowel operation or resection earlier after onset of symptoms. The development of recurrence after bowel resection, although occurring in a lower percentage of patients, was significantly shorter than in the young adults (3.7 years vs. 5.8 years, p < 0.02). Arthritic extraintestinal manifestations were equally frequent in both groups, but elderly patients had significantly less relatives in the first or second degree affected by CD (3.1% vs. 12%, p < 0.02). We conclude that the diagnosis Crohn's disease is more readily established in elderly patients. Moreover, these patients less frequently have abdominal pain/cramps as a presenting symptom, a shorter time interval between onset of symptoms and first resection, and subsequent recurrence of the disease. In addition, elderly CD patients have less relatives affected by the same disease. Thus, CD in the elderly appears to be characterized by a more rapid development.

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In vivo and in vitro invasion in relation to (into embryonic chick heart fragments), E-cadherin expression in vivo and in vitro and in vitro production of u-PA and t-PA. These parameters were chosen in view of their purported role in extracellular matrix degradation and intercellular adhesion, which are all involved in the invasive and metastatic cascade. Invasion in vitro was not predictive for invasion or metastasis in vivo. In the cell line which showed invasion in embryonic chick heart tissue, heterogeneous E-cadherin expression was observed in vitro together with a relatively high production of u-PA. The non-invasive cell lines showed in vitro homogeneous expression of E-cadherin with a relatively low production of u-PA. In vivo expression of E-cadherin was either absent or heterogeneous. We conclude that: (1) colorectal carcinoma xenografts show site-specific modification of in vivo invasive and metastatic behaviour; (2) invasion in vitro does not correlate with invasion and metastasis in vivo; (3) in vitro non-invasion might be associated with homogeneous E-cadherin expression and low production of u-PA; (4) E-cadherin expression in vitro differs from E-cadherin expression in vivo. The results support the notion that the microenvironment in which cancer cells grow is one of the factors involved in the regulation of invasive and metastatic behaviour.

These data do not support the hypothesis that metallothionein expression is a determinant of response in ovarian cancer. There is some preliminary evidence from the study of paired samples which indicates that cytotoxic chemotherapy may increase metallothionein expression. An increase in metallothionein was also seen in the study using unmatched biopsies although this did not attain statistical significance, due in part to the large inter-patient variability in expression of this protein.