SummaryThrombospondin (TSP), a large glycoprotein present in platelets, and various normal and tumor tissues, has recently been shown to promote cell adhesion and platelet aggregation. Most importantly because TSP has been shown to promote metastasis of melanoma tumor cells to the lung in a murine model (1) and since thromboembolic events commonly occur in patients afflicted with metastatic tumors, we explored the role of TSP in human cancer by measuring TSP blood levels in patients with various malignant neoplasms. Blood TSP levels were measured by indirect enzyme-linked immunoadsorbent assay (ELISA) from 20 control subjects, 22 patients with gastrointestinal (GI) cancer, 18 patients with breast cancer, and 17 patients with lung cancer. Control subjects consisted both of healthy subjects and acutely ill patients with no malignancies. TSP levels of both healthy and acutely ill controls were found to range between 245-440 μg/ml with a mean of 365 μg/ml. In contrast, elevated levels of TSP greater than the mean value of 400 μg/ml for controls ranging between 590-3,650 μg/ml were found in 20/22 (91%) patients with GI malignancies, 13/18 (72%) patients with breast cancer, and 15/17 (88%) with lung cancer. Mean TSP levels of GI, breast, and lung cancer patients were 3, 2, and 3 fold greater than controls, respectively. Increased blood TSP levels in patients were not due to increased levels of platelets since both control and patient groups had platelet counts within the normal range. These results suggest that TSP may play a role in tumor cell metastasis in man and could serve as a blood marker for metastasis.

Background. Thrombospondin is a high molecular weight glycoprotein, originally described as a secretion product of platelets, that functions as an adhesive protein in cell‐cell and cell‐substratum interactions. It promotes metastases in the murine model. Plasma thrombospondin has been shown to be elevated in patients with disseminated breast, lung, and gastrointestinal malignancies. Methods. Blood samples were collected by venipunc‐ture into cubes containing ethylenediamine tetraacetic acid as anticoagulant. They were placed on ice immediately and centrifuged under refrigerated conditions. Plasma was removed and frozen until thrombospondin was quantitated by a competitive enzyme‐linked immu‐nosorbent assay. Wilcoxon's two‐sample rank‐sum test was used to evaluate differences between the patient and control groups. Results. The median plasma thrombospondin level was significantly higher in the patient group compared with the control group, and it was directly correlated with stage of disease. There was no correlation between platelet count and thrombospondin level. Conclusions. Tumor‐synthesized thrombospondin could explain the elevated levels in the patent group and also the observation of the correlation between the thrombospondin level and tumor burden. Its function as an adhesive protein may allow it to act as the mediator of metastases. thrombospondin may promote or mediate the metastatic process through its function in cell adhesion. Cancer 1994; 73:2853–8.

Most practicing oncologists are committed to the concept of prospective clinical trials but, because of multiple logistic and perceptual deterrents, actually enter only a small portion of their patients into such studies. Physician concerns include discomfort with placebo or “no treatment” randomizations, the burden of cumbersome monitoring of protocol patients, and fear of displeasing referring physicians. Patients have difficulty accepting the uncertainty of randomized trials, particularly those with a placebo arm. They resent the inconvenience and expense of extra visits and studies associated with protocol participation. Informed consent documents are often complex and their intent misconstrued by patients. Rigorous eligibility requirements, although necessary for accurate analysis, reduce accrual. Multiplicity of protocols, with the resulting necessity to prioritize, rapid closure of Phase II studies for common tumors, and negative public attitudes reinforced by the media are significant deterrents to clinical trial participation. Increasing accrual is a daunting challenge to the physician. Simplification of burdensome data collection, consent forms, and institutional review board procedures will reduce reluctance to participate. Most important, physicians must be educators, emphasizing the advantages of clinical trials to their patients and their families, their colleagues, and the public.

In conclusion, whereas FOBT was unaffected by family history of CRC, screening colonoscopy was more frequent among women with a reported family history and differed with the degree of kinship of the affected relatives. The high rate of colonoscopy observed among subjects with first- and second-degree relatives is likely due to physician participation in screening decisions.

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