Biomedical subjects

A K Gregorakis

Publications and source records attributed to A K Gregorakis.

4 recordsLinked to original sources

PubMed2003

Immunohistochemical localization of human kallikreins 6, 10 and 13 in benign and malignant prostatic tissues.

Human kallikreins 6, 10 and 13 (hK6, hK10 and hK13) are expressed by many normal, mainly glandular tissues, including prostatic epithelium. Some kallikreins may function as tumor suppressors or are downregulated during cancer progression. The aim of this study was to evaluate the immunoexpression of these kallikreins in benign and malignant prostatic tissues and correlate their expression with prostate cancer (PC) prognosis. Included in the study were 25 cases of nonmalignant prostate and 179 cases of PC. Among them, 122 PC cases were immunostained for hK6, 94 for hK10 and 113 for hK13, respectively. The follow-up period for a subset of 68 patients who had undergone radical prostatectomy (RP) was 1-58 months (mean=13.4 +/- 1.7 and median=8.0 months). A cutoff value of 0.2 microg/l of serum PSA was established as a biochemical recurrence threshold. Follow-up information was available for 26/55 RP cases stained for hK6, 14/32 cases stained for hK10 and 25/59 cases stained for hK13. Gleason score (GS) 7 carcinomas were stratified as 7a and 7b, according to the primary grade. PC with GS 2-7a were histologically categorized as low malignant (LM) and PC with GS 7b-10 as high malignant (HM). The immunohistochemical method of streptavidin-biotin-peroxidase using monoclonal and polyclonal antibodies was performed. In the benign prostate and in prostatic intraepithelial neoplasia, a cytoplasmic immunostaining of varying intensity was evident. In PC, the immunoexpression of all kallikreins was decreased: 102/122 cases (84%) were positive for hK6, 73/94 (78%) for hK10 and 97/113 (86%) for hK13, respectively. A statistically significant difference in expression was found, in comparison to nonmalignant prostates (P=0.029, 0.009 and 0.045, respectively). Also, a positive correlation was observed between the immunoexpression of these three kallikreins. Concerning the histological grade, HM-PC expressed all three kallikreins with a slightly higher percentage than LM-PC: 79 vs 88% for hK6, 76 vs 79% for hK10 and 76 vs 92% for hK13. These differences were statistically significant only in the case of hK13 (P=0.024). Serum PSA did not correlate with kallikrein immunoexpression in PC. Furthermore, there was no significant correlation between kallikrein expression and pathological stage or recurrence, in the cases of RP. All three kallikreins are expressed in the nonmalignant and malignant prostate, with cancer tissues demonstrating slightly lower expression. Expression levels did not correlate with aggressiveness and they do not seem to have value for prostate cancer prognosis.

Humans↗

PubMed2000

Comparison of the percent free prostate-specific antigen levels in the serum of healthy men and in men with recurrent prostate cancer after radical prostatectomy.

The percentage of free PSA in serum is currently used to better discriminate between patients with prostate cancer and patients with benign prostatic hyperplasia, in prostate cancer screening programs. We measured using non-competitive immunological techniques, the total PSA and free PSA in post-surgical serum of prostate cancer patients who underwent radical prostatectomy and then relapsed. We compared these data with those of a group of 40 age-matched men with no evidence of prostatic disease. Although in general, patients with prostate cancer had lower percentage of free PSA in serum in comparison to the controls, a subset of these patients (approximately 20%) had percent free PSA significantly higher than the levels considered as exclusive of prostate cancer in screening programs. We also found that percent free PSA does not correlate significantly with most of the standard clinical or pathological indicators of prostate cancer aggressiveness. Only a weak negative association with Gleason Score was observed. The percent free PSA in serum of relapsing prostate cancer patients varies within a relatively wide range and does not correlate significantly with indicators of cancer aggressiveness. The use of percent free PSA for excluding prostate cancer in screening programs must be approached with caution until the mechanism of low percent free PSA in the majority but not all prostate cancer patients is elucidated.

Aged↗

PubMed1998

Prostate-specific membrane antigen: current and future utility.

Prostate cancer is the most common cancer and the second leading cause of cancer-related death among men. New prostatic markers are needed to increase diagnostic and prognostic effectiveness. One such new marker is prostate-specific membrane antigen (PSMA). PSMA is a highly prostate-restricted membrane glycoprotein that is expressed in normal prostatic epithelial cells and elevated in prostate cancers, especially in poorly differentiated, metastatic, and hormone refractory carcinomas. It has been measured in serum with immunocompetitive and Western blot assays, and its levels have been found to be correlated with the prediction of treatment failure and disease prognosis. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays with primers specific for PSMA have been shown to be more effective than PSA-specific primers in detecting hematogenous circulating prostate cancer cells; however, no clear benefit in patient staging or utility as a predictor of clinical outcome or response to treatment has so far been obtained using RT-PCR methods. PSMA is currently utilized as an immunoscintigraphic target using the antibody conjugate CYT-356 (ProstaScint; Cytogen, Princeton, NJ) and has been shown to have clinical value, particularly in detecting occult prostate cancer. Another current application of PSMA is in immunotherapy of prostate cancer, in which promising results have been obtained in a phase I trial, and a phase II trial is underway. The research summarized in this article indicates that PSMA is an excellent target for diagnostic and therapeutic applications in prostate cancer.

Antigens, Neoplasm↗

PubMed1997

Comparison of serum PSMA, PSA levels with results of Cytogen-356 ProstaScint scanning in prostatic cancer patients.

BACKGROUND: Stored serum from clinical trial cases undergoing ProstaScint (CYT-356) scanning were available for Prostate Specific Membrane Antigen (PSMA) assay. Prostate Specific Antigen (PSA) levels had already been determined. This provided an opportunity to see what correlations existed between the serum markers and the ProstaScint scan. A group of patients had the studies preprostatectomy, whereas another group had the studies postprostatectomy. METHODS: The scan results, serum PSA, serum PSMA, and clinical data were separately analyzed. PSMA serum levels were determined by Western blot. RESULTS: Preoperatively, radical prostatectomy patients showed a correlation between serum PSA or PSMA levels and the ProstaScint scan in the total group (n = 86), or in an untreated group (n = 38). Preoperatively, PSMA correlated with the pathological stage, whereas PSA correlated with the scan. Postoperatively, only PSMA serum levels correlated with the scan in an untreated group (n = 40). CONCLUSIONS: Preoperatively or postoperatively, Western blot PSMA serum levels predict the stage of disease or local, regional, or distant metastases, as shown by ProstaScint scan. Both the scan and the serum tests provide prognostic information and evaluate the extent of disease to a more significant degree than previously possible.

Adult↗