No abstract

It has been shown that RT-PCR is a powerful tool to detect CEA mRNA in the lymph nodes or the peripheral blood. This is potentially very useful to determine high-risk patients for metastasis. Serial analysis is warranted to assess the long-term significance of this method and its therapeutic and prognostic implications.

A novel member of the human frizzled (Fz) gene family was cloned and found to be specifically expressed in 3 of 13 well differentiated (23%), 13 of 20 moderately differentiated (62%), and 12 of 14 poorly differentiated (

The cDNAs of a putative growth factor-bound (Grb) 7 signal transduction molecule and Grb7V novel splice variant were isolated from an invasive human esophageal carcinoma. Although both Grb7 isoforms share homology with the Mig-10 cell migration gene, the Grb7V isoform lacks 88 base pairs in the C terminus; the resultant frame shift leads to substitution of an SH2 domain with a short hydrophobic sequence. The wild-type Grb7 protein, but not the Grb7V isoform, is rapidly tyrosyl phosphorylated in response to EGF stimulation in esophageal carcinoma cells. Analysis of human esophageal tumor tissues and regional lymph nodes with metastases revealed that Grb7V was expressed in 40% of Grb7-positive esophageal carcinomas. More importantly, Grb7V expression was enhanced after metastatic spread to lymph nodes as compared to the original tumor tissues.

Detection of the mRNA of selected genes by reverse transcriptase-polymerase chain reaction (RT-PCR) is a sensitive and powerful tool for detecting cancer cells in bone-marrow or peripheral-blood samples. In this study, we determined whether carcinoembryonic antigen (CEA) mRNA is detectable in the peripheral blood of patients with gastrointestinal or breast cancer. In addition, we studied selected patients undergoing surgical procedures to assess whether tumor manipulation during operation enhances cancer-cell dissemination. Peripheral blood from 55 patients with gastrointestinal or breast cancer and from 22 control cases was analysed for CEA mRNA using RT-PCR. For 15 selected cases undergoing curative surgery for cancer, samples were also obtained during and after surgery. Breast cancer is conceptually accepted by many investigators as a systemic disease (Brown et al., 1995;Cote et al., 1991). This means that early breast cancer or minimum-sized breast cancer can spread via the blood-stream or lymphatic system to form metastatic foci in distant organs. We have considered that the same situation might exist in gastrointestinal cancers. It was, however, difficult to prove this concept due to the limitcd techniques available. Reccnt dcvelopments in molecular technology now enable us to detect small numbers of circulating cancer cclls in the peripheral blood or bone marrow (Johnson et a/., 1995; Smith et al., 1991).In this study, we detccted the presence of carcinoembryonic antigen ( 1995). If CEA mRNA is detected in blood samples, this implies the presence of ectopic, and hence presumably malignant CEA-expressing cells. One potential problem is that the CEA gene family includes a number of homologous genes partly expressed in granulocytes, which may produce falsepositive results (Stoffel et al., 1993). To overcome this problem, CEA-specific amplification has been developed using welldesigned DNA primers (Gerhard et al., Neumaier el al., 1995). On the basis of the results obtained in our present study, we discuss the significance of the presence of CEA mRNA in the peripheral blood of patients. In addition, to examine the effect of tumor manipulation during operation (Brown et ab, 1995; Nishizaki et aL, 1990), we applied the RT-PCR assay to peripheral blood samples taken from patients before, during and after operation. MATERIAL A N D METHODS PatientsFifty-five patients aged between 31 and 76 years were evaluated; these included 6 with esophageal cancer, 20 with gastric cancer, 20 with colorectal cancer and 9 with breast cancer. Of these, 14 patients including 7 with stage-IV gastric cancer, 6 with Dukes' D colorectal cancer and 1 with stage-IV breast cancer were shown to have distant metastases which were confirmed by chest X-ray, computed tomography, magnetic resonance imaging or ultrasonography. In these 14 advanced cases, a simple resection of the primary lesion was performed in 2 of 7 cases of gastric cancer, 4 of 6 cases of colorcctal cancer and 1 case of breast cancer. The other 7 far advanced cases receive...