Antiproteolytic Activity of Human Serum with Particular Reference to Its Changes in the Presence and Considerations of Its Use for Detection of Malignant Neoplasia. ∗

Abstract

Lacking a specific test for malignant neoplastic disease (cancer), it is possible that something short of this with a high degree of correlation, analogous to the serological test for syphilis, will be of value in selecting patients for more detailed examination than that feasible in the customary screening process of a “Cancer Detection Clinic.” Many investigators have reported tests with this object in mind, without producing convincing evidence of a sufficient correlation with the presence or absence of malignant tumor. A review of these contributions will be undertaken in a later detailed presentation. Many of these tests are concerned with alterations in coagulation of the blood or its capacity to inhibit various enzymes. Another similarity is that they tend to give false positive reactions in the same types of pathologic conditions, other than malignant tumors.

These observations led us to believe that the basic mechanism might be an alteration in the proteolytic-antiproteolytic balance of the serum. Brieger and Trebing 1 suggested the use of the antifibrinolytic reaction of serum as a test for malignancy. Other reports by Von Bergmann and Meyer 2 , Herzfeld 3 , Roche 4 and many others were critically reviewed by Weil. 5

This approach was discarded because of the false positive reactions and the subjective nature of the test and the fact that it was considered a cachexia reaction. Contributions to our understanding of the antiproteolytic response since that time have been reviewed by Grob 6 and Clark et al. 7

A simple, reproducible, objective test of antiproteolytic (antitryptic) activity in serum was developed in this laboratory largely as a result of work by one of us (D.G.C.C). This test is performed as follows.