A MORE OBJECTIVE STAGING OF ADVANCED PROSTATE-CANCER - ROUTINE RECOGNITION OF MALIGNANT ENDOCRINE STRUCTURES - THE ASSESSMENT OF SERUM TPS,PSA, AND NSE VALUES

Bone scans, serum tissue-specific polypeptide antigen (TPS), prostate specific antigen (PSA), and neuronspecific enolase (NSE) were assessed in a total of 80 hormonally treated prostate cancer patients. Thirty- nine patients were free of osseous lesions; in 8 subjects, 3 or fewer scintigraphic hot spots were found; in 29 patients, more then 3 bone l esions were recorded. In 3 patients, a partial contribution of endocri ne cell cancer structures was found, while in one patient, a homogenou s small cell carcinoma was detected at autopsy. Measurement of the ser um PSA test showed a clear-cut rise from stage DO subjects to stage D2 patients, with a small number of bone lesions (greater than or equal to 3). However, a relative decrease in the mean PSA level was measured with further progression in a number of hot spots in bone (>3). Andro gen threshold that is critical for the induction of the PSA (and PAP) expression seems to differ markedly in various cell subpopulations tha t arise during adenocarcinoma dedifferentiation. This fact explains no t only the rise in serum PSA in the majority of progressive and previo usly castrated subjects after an initial period of hormonal responsive ness, but also a relative decline of androgen-dependent PSA expression with further tumor progression. Localized disease was accompanied wit h normal or just slightly elevated TPS concentration. In metastatic tu mors, serum TPS values revealed a steady increase with the progression in bone. These data seem to reflect not only an increase in tumor pro liferation rate with progressively transformed genome, but also the ri se in the number of proliferating cells. The presence of nonepithelial transformed tumor structures, such as small cell cancer within a bulk of adenocarcinoma, reduces or normalizes numerical serotests values o f both TPS and PSA even during tumor progression. The extent of such d ecline depends upon the bulk of the endocrine component. The assessmen t of the above parameters, especially when associated with elevated pl asma NSE concentrations, may help in distinguishing an advanced adenoc arcinoma with and without elements of malignant neuroendocrine structu res. The proposed approach, modified by applying corresponding organ-s pecific markers, may be checked for its possible general use in stagin g protocols of various heterogeneous tumors. (C) 1994 Wiley-Liss, Inc.