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T A Stamey

Publications and source records attributed to T A Stamey.

At least 19 recordsLinked to original sources

Limitations of serum prostate specific antigen in predicting peripheral and transition zone cancer volumes as measured by correlation coefficients.

PURPOSE: We reexamined the relationship between preoperative serum prostate specific antigen (PSA) and prostate cancer volume in 290 patients who underwent radical prostatectomy. MATERIALS AND METHODS: Serum samples from 290 consecutive patients were remeasured with the automated monoclonal-monoclonal Tosoh AIA-600 assay. These values were correlated with individual cancer volume by measuring Pearson correlation coefficients (r). RESULTS: Cancer was noted in the transition zone in 31 patients and in the peripheral zone in 259. Of the peripheral zone cancers 133 (51.4%) were organ confined and 126 (48.6%) were nonorgan confined, including 12 (9.5%) with histologically confirmed lymph node metastasis (stage D1). The 259 peripheral zone cancers had a correlation coefficient with PSA (r = 0.499, p < 0.0001). After distributing the 259 cases into cancer volume groups we found a large overlap in mean preoperative serum PSA, including 65 with 50% or greater Gleason grade 4 or 5 disease (r = 0.508). The correlation coefficients of cancer volume with PSA in 133 organ confined cancers, 114 nonorgan confined cancers without lymph node metastases and 12 nonorgan confined cancers with positive lymph nodes were 0.382, 0.438 and 0.363, respectively. The 31 transition zone cancers showed a correlation coefficient with PSA (r = 0.81). After excluding 2 cases with extreme PSA and cancer volume the correlation coefficient decreased (r = 0.077). CONCLUSIONS: Even when remeasured with an automated monoclonal-monoclonal assay serum PSA alone is unable to predict preoperatively cancer volume or distinguish between organ and nonorgan confined cancer in peripheral and transition zone tumors of the prostate.

Autoanalysis

Molecular mass and carbohydrate structure of prostate specific antigen: studies for establishment of an international PSA standard.

Despite the widely accepted use of prostate specific antigen (PSA) as a marker of prostate cancer, this molecule has not yet been completely characterized. Past studies have well established, however, using both amino acid and cDNA sequencing techniques, that PSA contains 237 amino acids, with a molecular mass of 26,079 Da for the peptide moiety of the molecule. The present study reports analysis of this protein by ion spray mass spectrometry (ISMS) and analysis of its carbohydrate moiety by NMR spectroscopy. The predominant PSA molecular species detected by ISMS was at relative molecular mass (M(r)) of 28,430, indicating that PSA contains a carbohydrate residue of M(r) 2,351, for a total percentage of carbohydrate of 8.3%. Analysis of PSA by SDS-PAGE, however, showed a M(r) of 32,000 to 33,000, suggesting an overestimation of the molecular weight by the latter technique. The complete primary structure of the PSA carbohydrate chain was determined by NMR spectroscopy in combination with carbohydrate composition analysis. The experimentally determined carbohydrate content of PSA confirms that only one N-glycosylation site is occupied in the protein. The proposed carbohydrate structure is a diantennary N-linked oligosaccharide of the N-acetyllactosamine type, with a sialic acid group at the end of each of the two branches. In addition, our data indicate that approximately 70% of the PSA molecules contain a fucose group in the core chitobiose moiety. The calculated molecular weight of this carbohydrate structure (M(r) 2,351.8) is in excellent agreement with the predicted molecular weight of the carbohydrate group, based on the M(r) 28,430 for PSA measured by ion spray mass spectrometry and M(r) 26,079 calculated from the consensus sequence for the peptide portion of the molecule. ISMS of PSA is thus proposed as a convenient and reliable method of quality control, an indispensible step towards international standardization of this very important tumor marker for detection and monitoring of prostatic diseases, especially prostate cancer.

Amino Acid Sequence

Identity of PSA purified from seminal fluid by different methods: comparison by amino acid analysis and assigned extinction coefficients.

To determine the true extinction coefficient of prostate specific antigen (PSA) and to measure any differences in PSA when isolated from seminal fluid by four different published methods, we studied 10 different lots of PSA by quantitative amino acid analysis. Despite an expected PSA concentration of 1 mg/ml based on gravimetric analysis at an average optical density of 1.45 at 280 nm, we recovered only 0.79 mg/ml by quantitative amino acid analysis (range 0.752 to 0.820 mg/ml with a coefficient of variation [C.V.] of 3.3% among the 10 lots). The concentration of 0.79 mg/ml was based on a molecular weight of 28,430 daltons for glycosylated PSA determined by ion spray mass spectroscopy [Bélanger et al: Prostate, 27:187-197, 1995]. From these 10 amino acid analyses, we calculated the extinction coefficient of PSA at 280 nm as 1.84 +/- 0.04 ml x mg-1 x cm-1 (range 1.78 to 1.90 with a C.V. of 2.2%). Similar concentrations of PSA were obtained by amino acid analysis regardless of the method of purification. These observations support the presence of a single form of PSA in seminal fluid and are consistent with the molecular evidence that PSA is transcribed from a single gene locus on the long arm of chromosome 19 [Riegman et al.: Genomics 14:6-11, 1992]. They do not support the recent contention by the Roswell Park group that the PSA they isolated in 1979 [Wang et al.: Invest Urol 17:159-163, 1979; Wang et al.: Prostate 24:107-108, 1994] is different from p30 reported a year earlier [Sensabaugh: J Forensic Sci 23:106-115, 1978].

Amino Acids

Prediction of prostate cancer volume using prostate-specific antigen levels, transrectal ultrasound, and systematic sextant biopsies.

OBJECTIVES: Prostate-specific antigen (PSA) levels, transrectal ultrasound, and systematic sextant biopsies have each shown limited ability to predict prostate cancer volume. In combination, these studies may allow more accurate estimation of volume and prognosis. METHODS: One hundred twenty-four patients were evaluated prior to radical prostatectomy. Interactive stepwise multiple regression and separate logistic regression analysis were performed for prediction of prostate cancer volume and volume range. RESULTS: The cancer volumes calculated correlated with the volumes in the radical prostatectomy specimens with R2 of 0.76. Cancers were predicted to be in the volume range associated with poor prognosis (more than 12 cc) or clinically insignificant cancer (less than 1.0 cc) with bias corrected error rates of 5.3% and 10%, respectively. CONCLUSIONS: The formula for prediction of cancer volume correlates well with actual cancer volume in 92 patients but is not adequate to predict volume for an individual patient. The formulas for prediction of volume range show promising predictive ability and may be useful if the extent of disease is unclear.

Aged

DNA ploidy status.

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DNA, Neoplasm

Core cancer length in ultrasound-guided systematic sextant biopsies: a preoperative evaluation of prostate cancer volume.

OBJECTIVES: Evidence has been presented that biologic aggressiveness of prostate carcinoma increases with volume and that cancers less than 0.5 cc may be regarded as clinically insignificant for immediate treatment. We have analyzed the ability of core cancer length on needle biopsy to predict cancer volumes near the 0.5 cc threshold for distinction between incidental versus clinical carcinoma. METHODS: Systematic sextant transrectal ultrasound-guided prostate biopsies were performed on 110 men who then underwent radical prostatectomy for adenocarcinoma. The core cancer length within each biopsy was compared with the volumes of clinical and incidental carcinomas in the prostatectomy specimen. RESULTS: Among incidental (nonpalpable) cancers, 14% of those under 0.2 cc were detected, but 44% at 0.2 to 0.5 cc and 92% of those more than 0.5 cc were detected. Among clinically suspected carcinomas, 2 mm or longer core cancer length reliably predicted a cancer of 0.5 cc or larger, but among incidental cancers, it predicted a tumor of 0.2 cc or larger. A 3-mm core cancer length threshold predicted 0.5 cc for both groups. The high frequency of incidental cancers under 0.5 cc impaired the predictive value of multiple positive needle cores. Bilateral positive biopsy results indicated bilateral extension of clinical cancer in only 59% of cases. CONCLUSIONS: A core cancer length of 3 mm or more on one or two needle biopsies reliably predicts cancer of clinically significant volume (0.5 cc or larger). The high detection frequency of smaller incidental carcinomas on biopsy impairs the reliability of volume estimation from multiple positive needle cores and mandates that treatment decisions be made with knowledge of core cancer length.

Adenocarcinoma

Incontinence and vesical neck strictures following radical retropubic prostatectomy.

OBJECTIVES: To evaluate the incidence and severity of vesical neck strictures and urinary incontinence after radical retropubic prostatectomy (RRP) for prostate cancer. METHODS: Between August 1983 and December 1991, 481 consecutive patients underwent RRP by 1 of 2 senior surgeons. Strictures were treated by passing a urethral sound. Incontinence was measured by asking patients for a daily "pad count" of pads required to control urinary leakage. Results were compared to patient age, tumor volume, number of neurovascular bundles spared, preoperative urinary complaints, and previous transurethral resection of the prostate. RESULTS: Of 456 patients with adequate follow-up to determine stricture formation, 82.5% had no strictures, 6.8% required a single dilation, 3.7% required 2 dilations, 3.1% required 3 dilations, and 3.9% required more than 3 dilations. Risk of stricture formation was unrelated to every variable studied. Of 458 patients with adequate follow-up to determine recovery of continence, 80.1% required no pads, 8.1% required 1 to 2 pads a day, 6.6% required 3 to 5 pads a day, and 5.2% were totally incontinent 1 year or more after surgery. Incontinence was closely associated with postoperative urinary urgency. CONCLUSIONS: Strictures are a common but easily managed complication of RRP for prostate cancer. Despite substantial surgical experience, we report a somewhat higher rate of postoperative incontinence than other recently reported series. Our experience is more closely matched by published surveys of patient-reported complications after RRP.

Aged

Serum prostate-specific antigen and the biologic progression of prostate cancer.

OBJECTIVES: We have previously shown that serum prostate-specific antigen (PSA) is proportional to prostate cancer volume and that progression of prostate cancer is proportional to volume, but other investigators have not found serum PSA to be as useful in predicting pathologic stage at the time of radical prostatectomy. Because our series is the only study to examine prospectively all radical specimens at 3-mm intervals, we have examined the relationship between serum PSA and the morphologic indicators of cancer progression in our first 350 radical prostatectomies. METHODS: Preoperative serum PSA level was tabulated in 350 consecutive patients with prostate adenocarcinoma and compared with morphologic variables in the radical prostatectomy specimen. Morphologic variables included cancer volume, histologic grade, capsular penetration, seminal vesicle invasion, and lymph node metastasis. RESULTS: Serum PSA showed strong correlation with all morphologic variables, which were highly intercorrelated. Serum PSA level was strongly correlated with cancer volume, histologic grade, and frequency of regional spread to lymph nodes. Close intercorrelations found between all variables were translated into a scale relating each level of serum PSA elevation to stage of disease in morphologic terms. Using this scale, serum PSA level can contribute to patient evaluation and treatment decisions in men with prostate cancer. CONCLUSIONS: Serum PSA is primarily determined by prostate cancer volume and secondarily by the percentage of high-grade cancer (Gleason grades 4 and 5) in the prostate. Because of this basic relationship, serum levels of PSA provide a clinically useful estimate of morphologic findings in the prostate. Serial PSA determinations should reflect the growth of the cancer as well as the gradual evolution of more malignant cells with the passage of time. The use of a serum PSA-based rating scale can contribute to patient evaluation and treatment decisions in men with prostate cancer.

Adenocarcinoma

Correlation between serum prostate specific antigen levels and the volume of the individual glandular zones of the human prostate.

To analyze the correlation between serum prostate specific antigen (PSA) levels and the volume of the individual glandular zones of the human prostate, we examined 31 cystoprostatectomy specimens as well as 13 radical prostatectomy specimens with a prostate cancer volume of 0.3 cc or less, no bladder cancer infiltrating the prostate, no granulomas or severe inflammation, as well as no patient history of radiation, transurethral resection of the prostate or hormonal treatment. The volumes of the peripheral zone, transition zone and central zone were separately determined by outlining the zonal boundaries during microscopic examination of all slides at each level of section. PSA was measured by the Yang polyclonal assay. In the univariant regression analysis the correlation coefficients among serum PSA and transition zone, peripheral zone and central zone volumes were 0.934, 0.546 and 0.368, respectively, strongly suggesting that most PSA leakage from the prostate into the serum comes from the transition zone. The regression of serum PSA and transition zone volumes leads to a prediction of approximately 0.261 ng./ml. PSA per gm. benign prostatic hyperplasia (BPH) plus an intercept of 0.878, a number in keeping with our 1987 estimates of 0.3 ng./ml./gm. BPH. The volumes of the 3 zones appeared to be independent variables. Transition zone volume showed the greatest variation because of BPH. The mean average ratio of peripheral zone volume to central zone volume was nearly 3:1. These data strongly support the concept of age-adjusted PSA levels, since most of the increase in size of the prostate with increasing patient age comes from the transition zone from which BPH develops.

Adult

Clinical usefulness of free and complexed PSA.

We selected serums from 51 fully characterized prostate cancer patients and 48 biopsy-proven BPH patients in order to test the ability of the ratio of the free/total PSA in distinguishing between CaP and BPH patients in the best case scenario. The 51 cancer patients had cancer volumes ranging from 2.0-17.8 mL and had a median % free PSA of 8.9%. The 48 BPH patients, which had prostate volumens ranging from 36.9-313.8 mL, had a median % free PSA of 16.5%, almost twice that of the CaP patients. We also examined the physiological variation of serums drawn on the same patient over a reasonably short time (mean of 22 days). The variation between consecutive redraws on the same patient was measured to be 30% (95% confidence interval) in the PSA range of 4-10 micrograms/L, measured on the Hybritech Tandem-R PSA Assay.

Humans

A universal calibrator for prostate specific antigen (PSA).

We describe for the first time a protocol to purify an in vitro made PSA-ACT complex to apparent homogeneity by using a combination of gel filtration and ion-exchange chromatography. The purity of the PSA-ACT complex was confirmed by gel electrophoresis and Western blot. Purification of the PSA-ACT complex was highly reproducible. An extinction coefficient of 1.0 and 280 nm (L x g-1 x cm-1) was assigned to the PSA-ACT complex based on amino acid analysis. Molecular weight was assigned by taking cDNA of ACT (plus 26% carbohydrate) and the molecular weight of PSA (28,430) which totals 89,280. Two common calibrators were made consisting of 100% PSA-ACT complex and/or 90% PSA-ACT complex plus 10% free PSA (90:10 calibrator). The 90:10 calibrator is recommended as a universal calibrator for the international standardization of PSA immunoassays.

Humans

Ultrasensitive assay of prostate-specific antigen used for early detection of prostate cancer relapse and estimation of tumor-doubling time after radical prostatectomy.

We used an ultrasensitive prostate-specific antigen (PSA) assay with a detection limit of 0.02 microgram/L for long-term monitoring of PSA changes in 5 patients who were cured by radical prostatectomy and in 10 patients who had failed prostatectomies; 5 patients who underwent cystoprostatectomy were also evaluated with one sample after surgery. Relapse-free periods, determined on the basis of criteria designed specifically for the ultrasensitive assay or proposed for other currently available PSA assays, were calculated for the patients with failed prostatectomies. Tumor-doubling times were also calculated, postsurgery, according to a model that assumes exponential tumor growth over time. We found that prostate cancer relapse, on average, could be diagnosed 420 or 883 days earlier with the ultrasensitive assay than with assays having detection limits of 0.1 or 0.3 microgram/L, respectively. Tumor-doubling times, calculated after radical prostatectomy, ranged from 67 to 568 days among the 10 patients. We also present evidence that even more-sensitive PSA assays might be able to further reduce the relapse-free periods in approximately 50% of the prostate cancer patients who ultimately relapse.

Fluoroimmunoassay

Purification and characterization of prostate-specific antigen (PSA) complexed to alpha 1-antichymotrypsin: potential reference material for international standardization of PSA immunoassays.

We describe for the first time a protocol to purify to apparent homogeneity an in vitro-prepared complex of prostate-specific antigen (PSA) and alpha 1-antichymotrypsin (ACT) by using a combination of gel filtration and ion-exchange chromatography. The purity of the PSA-ACT complex was confirmed by gel electrophoresis and Western blot. The PSA-ACT complex was stable in the pH range 6.0 to 7.8; it was also stable in various matrices, temperatures, and high concentrations of salt. Purification of the PSA-ACT complex was highly reproducible. An absorptivity of 0.99 L x g-1 x cm-1 at 280 nm was assigned to the PSA-ACT complex, based on amino acid analysis. Because PSA and ACT bind in a 1:1 molar ratio, we determined the molecular mass of the PSA-ACT complex as the mass encoded by the cDNA of ACT (plus 26% carbohydrate) plus the molecular mass of PSA (28,430 Da), which totals 89,280 Da. Using this material, we made two common calibrators, one of 100% PSA-ACT complex and one of 90% PSA-ACT complex plus 10% free PSA by volume (90:10 calibrator). Substitution of these calibrators for the manufacturers' calibrators in nine commercial immunoassays substantially reduced differences between immunoassays, especially for serum PSA values between 4 and 10 micrograms/L. The 90:10 calibrator is recommended as a universal calibrator for international standardization of PSA immunoassays.

Amino Acid Sequence

Interpretation of bilateral positive biopsies in prostate cancer.

PURPOSE: When 6 systematic prostate needle core biopsies are positive for cancer bilaterally, prediction of clinical cancer volume is limited by the unpredictable presence of contralateral incidental tumors. Criteria were sought to improve prediction. MATERIALS AND METHODS: Core cancer lengths were summed unilaterally (3 biopsies) and bilaterally (6) in 65 patients with bilateral positive cores. Of the patients 31 had true bilateral cancer spread and 34 had unilateral disease with contralateral incidental tumors. RESULTS: For both groups correlation with prostatectomy cancer volume (r = 0.65, p < 0.001) was the same for the sum of 3 ipsilateral cores as for all 6 cores. CONCLUSIONS: Core cancer length sum of 3 ipsilateral biopsies predicts the largest prostatectomy cancer volume as well as the bilateral sum. Contralateral biopsies do not contribute to prediction nor distinguish bilateral spread from contralateral incidental cancers.

Aged