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Jonathan I Epstein

Publications and source records attributed to Jonathan I Epstein.

At least 127 records · Page 7Linked to original sources
PubMed2003

Long-term cancer control of radical prostatectomy in men younger than 50 years of age: update 2003.

OBJECTIVES: To compare the cancer control in men younger than 50 years with that in older men treated with radical retropubic prostatectomy (RRP) for localized prostate cancer in a contemporary series. In the 1970s and 1980s, men younger than 50 years old represented approximately 1% of newly diagnosed prostate cancer cases. However, with the widespread use of serum prostate-specific antigen (PSA) testing and increased public awareness of prostate cancer, this figure has risen (3.7% to 4%). Previous studies, mostly carried out before the PSA era, reported conflicting data with respect to cancer control for these younger men treated with RRP. METHODS: We analyzed the data from 2897 men who underwent RRP between April 1982 and September 2001. Preoperative PSA level, clinical and pathologic stage, and biochemical recurrence were compared between 341 men younger than 50 years old and 2556 men 50 years old or older. Disease-free (PSA less than 0.2 ng/mL) survival rates were compared using Kaplan-Meier analysis. Pathologic staging was compared using logistic regression analysis. RESULTS: Men younger than 50 years old had pathologic variables and 5, 10, and 15-year biochemical disease-free survival rates comparable to men aged 50 to 59 years (88%, 81%, and 69% versus 87%, 78%, and 71%, respectively). However, younger men had a lower incidence of extraprostatic extension (25% versus 31%; P <0.02), seminal vesicle involvement (2% versus 6%; P <0.03), and positive surgical margins (3% versus 9%; P <0.03), a greater organ-confined disease rate (65% versus 49%; P <0.0001), and a trend toward greater 5, 10, and 15-year biochemical disease-free survival rates, which did not reach statistical significance, compared with men aged 60 to 69 years (84%, 74%, and 67%, respectively; P <0.09). Furthermore, younger men not only had a lower rate of extraprostatic extension (25% versus 36%; P <0.001), seminal vesicle involvement (2% versus 10%; P <0.001), and positive surgical margins (3% versus 9%; P <0.001) and a greater organ-confined disease rate (65% versus 36%; P <0.0001), they also demonstrated significantly (P <0.003) greater 5, 10, and 15-year biochemical disease-free survival rates compared with men aged 70 years or older (72%, 58%, and 58%, respectively). CONCLUSIONS: Men diagnosed with prostate cancer who are younger than 50 years of age and are candidates for RRP tend to have a greater probability of organ-confined disease than older men. Younger men also demonstrate greater long-term cancer control rates than older men.

Adenocarcinoma↗
PubMed2003

Probability of biochemical recurrence by analysis of pathologic stage, Gleason score, and margin status for localized prostate cancer.

OBJECTIVES: The Partin tables provide pretreatment information regarding the probability of various pathologic stages (eg, organ confined, extraprostatic extension, and seminal vesicle or lymph node involvement). Although the pathologic stage serves as an excellent surrogate for outcome after radical prostatectomy (RRP), many patients and physicians want to know how the predictions made from the Partin tables can be translated into long-term biochemical recurrence-free survival. In this work, we go beyond the pathologic outcomes predicted by the Partin nomograms to provide long-term biochemical recurrence-free estimates on the basis of the pathologic data obtained at RRP to help counsel patients after surgery for prostate cancer. METHODS: The study group comprised 1955 men treated by one surgeon with RRP and pelvic lymph node dissection for clinically localized disease (1989 to 2001). The patients were followed up for at least 1 year postoperatively, and the disease-free survival rates were determined using Kaplan-Meier analysis. RESULTS: The pathologic stages were as follows: organ confined in 57%, extraprostatic extension in 35%, seminal vesicle involvement in 4%, and lymph node involvement in 4%. The prostatectomy Gleason score distribution was as follows: 2 to 4 in 1%, 5 to 6 in 63%, 7 in 30%, and 8 to 10 in 6%. Overall, a positive surgical margin was present in 9.8%. On the basis of the prostatectomy Gleason score, pathologic stage, and surgical margin status, the probability of long-term biochemical recurrence-free survival was divided into four groups: excellent, good, moderate, and low. CONCLUSIONS: These simple to use and explain risk groups can be used to predict long-term biochemical recurrence-free survival from pathologic stage data obtained at surgery or predicted from the Partin tables, along with surgical margin status and Gleason score information obtained at RRP.

Adenocarcinoma↗
PubMed2003

The new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification for TA, T1 bladder tumors: is it an improvement?

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification of urothelial neoplasms of the urinary bladder was developed in an attempt to both improve upon prior classification systems as well as to adopt a classification system that would have widespread acceptance. Prior to this classification system, numerous diverse grading schemes for bladder cancer existed whereby the same lesion seen by different pathologists would result in very different diagnoses solely based on definitional differences of lesions. Another strength of the consensus classification system is that it provides detailed histological criteria for papillary urothelial lesions. In contrast, prior grading systems for bladder tumors were vague and subjective. The current classification system allows for designation of a lesion (papillary urothelial neoplasm of low malignant potential), which biologically has a very low risk of progression, yet is not entirely benign. In the past, these lesions were a source of controversy, as some experts in the field required very restrictive criteria for the diagnosis of papilloma and would label such lesions as malignant. Other experts in the field, not wanting to label a patient with such a low-grade papillary lesion as having carcinoma, would diagnose these lesions as papilloma. This intermediate category allows both schools of thought to diagnose a lesion as not fully malignant, yet still documents need for additional follow-up. Since its inception, several studies have been published documenting the relationship of tumors classified using the WHO/ISUP system to prognosis. These articles are summarized within this review.

Consensus↗
PubMed2003

The reporting of prostate cancer on needle biopsy: prognostic and therapeutic implications and the utility of diagnostic markers.

Prostate needle biopsy remains the gold standard for diagnosing prostate cancer. Prostate cancer on needle biopsy can be evaluated by numerous techniques of quantifying tumour extent, Gleason score, and the presence of perineural invasion (PNI). These modalities can help clinicians in assessing the risk of extraprostatic disease, progression likelihood, and in helping men with prostate cancer choose among therapeutic options. This review details the information that should be included in the routine pathology report. Recent advances in molecular biology of prostate carcinogenesis have identified many molecular markers for prostate cancer. While several are extremely promising as diagnostic immunohistochemical markers, other prognostic markers are not yet ready to be used in routine practice until they are validated by large prospective studies.

Biomarkers, Tumor↗
PubMed2003

Atypia in nonneoplastic prostate glands after radiotherapy for prostate cancer: duration of atypia and relation to type of radiotherapy.

It is unknown how long postradiation atypia of benign prostate glands persists and whether the type of radiation is a factor. Forty-four cases consisting of 37 needle biopsies and 7 transurethral resections of the prostate seen in consultation (January 1997 to September 2000) were studied. In two men (5%), the cases were initially sent without a history of radiotherapy. Thirteen patients had minimal cancer (one core) with the remaining showing no residual tumor. Twenty patients were treated with interstitial radiotherapy (brachytherapy) (IRT), 17 with external beam radiation (XRT), and 7 with a combination of both (CT). The time interval between the treatment and tissue sampling ranged from 8 to 72 months (mean 3 months). Slides were reviewed blindly to the type of radiation and the time interval. Radiation-induced atypia in nonneoplastic glands, stromal fibrosis, and vascular changes was scored separately 0-3, with 0 showing no radiation injury and grade 3 showing prominent nuclear atypia, stromal fibrosis, and vascular hyalinization. We derived a combined score for the epithelial atypia from 0 to 300 (% of glands x grade) for each biopsy. For each case, an overall grade from 0 to 3 was given separately for the stromal and vascular changes. Cases were divided into three groups based on time between treatment and biopsy: <24 months (n = 14), between 24 and 48 months (n = 19), and >48 months (n = 11). Because the scores for epithelial atypia with IRT and CT were the same, we combined them into one group. There was more atypia in cases treated with IRT/CT (mean score 190) than XRT (mean score 105) (p <0.00001). There was also a greater degree of stromal fibrosis with IRT/CT than XRT (p <0.04). There was no correlation between the type of treatment and the effect on vessels. There was no change over time in epithelial atypia in men treated with IRT/CT. With XRT, there was less epithelial atypia in cases biopsied >48 months after treatment (mean score 57) compared with those with a shorter interval between biopsy and treatment (mean score 132) (p = 0.02). Radiation atypia in benign prostate glands may persist for a long time after the initial treatment, resulting in a significant pitfall in evaluating prostate biopsies. Prominent radiation effect (100% of the glands showing grade 2 and 3 atypia) was detected up to 72 months in one of the patients treated with IRT. In some cases, the clinician may not be aware of a prior remote history of radiation or does not relay this history to the pathologist. The pathologist must recognize radiation atypia without relying on the clinician to provide this history. The type of radiation therapy (IRT/CT vs XRT) is a major factor in the degree and duration of postradiation epithelial atypia.

Adenocarcinoma↗
PubMed2003

Expression and diagnostic utility of alpha-methylacyl-CoA-racemase (P504S) in foamy gland and pseudohyperplastic prostate cancer.

Foamy gland and pseudohyperplastic carcinomas are two uncommon variants of prostate cancer and often pose diagnostic challenges on needle biopsies. Alpha-methylacyl-CoA-racemase (AMACR) is a recently discovered tumor marker whose expression is significantly upregulated in prostate cancer. However, the original works only studied ordinary prostate cancer without reference to specific morphologic variants. Therefore, the expression and diagnostic utility of AMACR in specific variants of prostate cancer are unknown. In addition, two different antibodies, one monoclonal and one polyclonal, were used in the previous studies. The goal of this study is to examine the expression pattern and diagnostic utility of AMACR in foamy gland and pseudohyperplastic prostate cancer and to compare the diagnostic utility of the two anti-AMACR antibodies in the same prostate needle biopsy series. Prostate cancer with foamy gland or pseudohyperplastic features was retrieved from the Johns Hopkins Hospital Surgical Pathology file. Thirty needle biopsies harboring prostate cancer with foamy gland features and 17 needle biopsies harboring prostate cancer with pseudohyperplastic features were available for this study. Immunohistochemistry for AMACR was performed with two antibodies, a monoclonal one (P504S) and a polyclonal one (AMACR-p), using previously published protocols. Immunohistochemistry for high molecular weight cytokeratin and p63 was performed to confirm the cancer diagnosis. The AMACR staining intensity was graded as negative, weak, moderate, and strong. Only the staining that was significantly stronger than that of background benign glands was considered positive. A total of 68% and 62% of foamy gland prostate cancer was positive for AMACR with P504S and AMACR-p antibodies, respectively. A total of 77% and 70% of pseudohyperplastic prostate cancer was positive for AMACR with P504S and AMACR-p antibodies, respectively. Staining was often heterogeneous with different staining intensities within the same lesion. The mean percentage of stained glands in positive cases was 74.4% (range 25-100%) with P504S and 78.9% (range 20-100%) with AMACR-p in foamy gland prostate cancer and 91% (range 10-100%) with P504S, and 86.7% (range 10-100%) with AMACR-p in pseudohyperplastic prostate cancer. Seven foci of high-grade prostatic intraepithelial neoplasia present in the study cases were all positive for AMACR. The two antibodies were not statistically different in their sensitivity and specificity. In conclusion, AMACR is potentially a useful diagnostic marker for foamy gland and pseudohyperplastic prostate cancer in the following setting. When the pathologist favors the diagnosis of these variants of cancer on routine stained sections and stains for basal cells are negative, yet still a definitive diagnosis of cancer is difficult because of the cancers' deceptively benign appearance, positive staining for AMACR can provide the additional confidence to establish a definitive malignant diagnosis. The major caveat in the interpretation of positive staining is that high-grade prostatic intraepithelial neoplasia cannot be in the differential diagnosis.

Biomarkers, Tumor↗
PubMed2003

Alpha-methylacyl-CoA racemase: a variably sensitive immunohistochemical marker for the diagnosis of small prostate cancer foci on needle biopsy.

Expression of the alpha-methylacyl-CoA racemase (AMACR) gene has recently been demonstrated by several groups to be markedly elevated in prostate cancer cells with little expression in benign prostate tissue and has been suggested as a molecular marker of prostate cancer on needle biopsy. There is scant data, however, as to the sensitivity and specificity of AMACR in the diagnosis of small foci of cancer on needle biopsy. A total of 209 needle biopsies of the prostate with small foci (<5% of a core) of prostatic adenocarcinoma were identified. A total of 175 cases were received in consultation by one of the authors (140 from a single institution and 35 from different outside institutions) and 34 cases were from our hospital file. Immunohistochemistry for high molecular weight cytokeratin and p63 was performed in all cases to confirm the diagnosis of cancer. Only AMACR staining that was significantly stronger than that of background benign glands was considered positive; 88% of all cases of prostate cancer were positive for AMACR. The sensitivity varied among the different groups: 100% for the in house cases, 87.1% for the cases from a single institution, and 80% for cases from different outside institutions. The mean percentage of stained glands in positive cases was 95.9%, with 150 (71.8%) cases showing 100% of the glands positive and 25 (12.0%) cases showing no staining. Because negative staining for basal cell markers, especially in a small focus of atypical glands, is not necessarily diagnostic of prostate cancer, positive staining for AMACR can increase the level of confidence in establishing a definitive malignant diagnosis. However, the sensitivity of AMACR staining may vary in specimens from different pathology laboratories, possibly related to differences in fixation and processing. It is important to optimize the staining technique for each laboratory and recognize that some small cancers on needle biopsy may be AMACR negative.

Adenocarcinoma↗
PubMed2003

Florid von Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma.

Florid von Brunn nests may mimic the nested variant of urothelial carcinoma. We examined formalin-fixed, paraffin-embedded tissue from 21 cases of florid von Brunn nests and 11 cases of nested variant of urothelial carcinoma. Morphologic features were recorded in detail. Also, cases were stained with monoclonal antibodies against MIB-1, p53, p27, and cytokeratin 20. Percentage positivity was calculated by counting 300 to 500 cells from each case. Clinical follow-up information was also obtained. Florid von Brunn nests from the bladder were comprised of large nests with regular spacing, and all the nests extended to the same horizontal level at the base of the proliferation. Central lumen formation was often seen within florid von Brunn nests, at times with cystic dilatation, such that there was a spectrum from proliferating von Brunn nests to cystitis glandularis to cystitis cystica. Small, crowded nests with variable spacing and an infiltrative base characterized nested variant of urothelial carcinoma. Four cases showed detrusor muscle invasion on biopsy with an additional case showing detrusor muscle invasion at cystectomy. One additional patient with nested variant of urothelial carcinoma had distant metastases and another had prostatic invasion. Nine of 21 florid von Brunn nests cases were from either the ureter or renal pelvis, whereas all cases of nested variant of urothelial carcinoma arose in the bladder. The ureteral and pelvic florid von Brunn nest cases showed smaller, more variable nests with irregular spacing closely mimicking nested variant of urothelial carcinoma but had a noninfiltrative base and often areas with either a lobular or linear array. Immunohistochemical studies showed nested variant of urothelial carcinoma to have higher MIB-1 expression (8.8% vs. 2.8%, P = 0.01). Nested variant of urothelial carcinoma had nonsignificantly higher p53 positivity (4.2% vs. 1.5%, P = 0.06) and lower p27 positivity (4.7% vs. 7.8%, P = 0.22). Cytokeratin 20 staining was not discriminatory. However, staining with each antibody was widely variable. Wide variation in staining for MIB-1, p53, p27, and cytokeratin 20 was seen in both florid von Brunn nests and nested variant of urothelial carcinoma, such that except for a few cases, a specific cutoff value could not be determined for diagnostic purposes. The findings underscore the importance of morphologic assessment in the distinction of florid von Brunn nests and nested variant of urothelial carcinoma.

Adolescent↗
PubMed2003

Quantitative GSTP1 methylation clearly distinguishes benign prostatic tissue and limited prostate adenocarcinoma.

PURPOSE: Hypermethylation of the glutathione S-transferase gene (GSTP1) is the most common (greater than 90%) reported epigenetic alteration in prostate cancer. It occurs early in cancer progression and it is a promising marker for detecting organ confined disease. To evaluate its use as a diagnostic tool for cancer we used quantitative GSTP1 methylation to test for the presence of cancer in 45 prostate needle biopsy samples. MATERIALS AND METHODS: Paraffin tissue samples from 45 patients with minute foci of intermediate grade prostatic adenocarcinoma or benign disease on needle biopsy were tested for GSTP1 hypermethylation using quantitative fluorogenic real-time methylation specific polymerase chain reaction. This assay was performed in blinded fashion without previous knowledge of the histopathological diagnosis. RESULTS: DNA from 29 of the 45 paraffin samples was amenable to polymerase chain reaction amplification. In these 29 samples GSTP1 methylation was detected in 11 of 15 cases of limited cancer and in 0 of 14 of benign disease (2-sided Fisher's exact test, p <0.0001). Thus, this assay had 73% sensitivity, 100% specificity, 100% positive and 78% negative predictive values. CONCLUSIONS: Quantitation of GSTP1 hypermethylation accurately detects the presence of cancer even in small, limited tissue samples. It represents a promising diagnostic marker that could be used as an adjunct to tissue biopsy as part of prostate cancer screening.

Adenocarcinoma↗
PubMed2003

Correlation of minute (0.5 MM or less) focus of prostate adenocarcinoma on needle biopsy with radical prostatectomy specimen: role of prostate specific antigen density.

PURPOSE: Few studies have examined the radical prostatectomy followup of a minute focus of adenocarcinoma on prostate needle core biopsy. MATERIALS AND METHODS: We searched the surgical pathology data base (1999 to 2000) for patients with a minute focus of Gleason score 6 adenocarcinoma (defined as a single focus less than or equal to a 40 x microscopic field) who subsequently underwent radical retropubic prostatectomy at our institution. Potentially insignificant tumors were defined as those with a radical prostatectomy tumor volume of less than 0.5 cc, Gleason score 6 or less and organ confined disease. RESULTS: A total of 54 patients (mean age 58 years, range 45 to 70) were evaluated. The average number of prostate cores per biopsy was 6.3. All had Gleason score 6 by study design. Mean prostate specific antigen (PSA) was 6.0 (range 0.8 to 15). Average tumor volume at radical prostatectomy was 0.39 cc. Of the 54 tumors 24 (44%) were 0.1 cc or less. Two-thirds of the tumors were clinically potentially insignificant. Using a PSA density (PSAD) cutoff of 0.15 we identified 30 of 36 patients (83%) with potentially insignificant tumors. Of those with a PSAD of 0.15 or less with clinically significant tumors, 5 of 6 still had relatively small, organ confined tumors with Gleason score less than 7. CONCLUSIONS: In the era of PSA screening most patients with a minute focus of Gleason score 6 or less adenocarcinoma on needle biopsy had potentially insignificant tumors. However, one-third of patients had clinically significant tumors warranting definitive therapy. The smallest focus of cancer on needle biopsy is not a guarantee of a clinically insignificant tumor. PSAD may have some value within this group in guiding clinicians and patients as to the likelihood of having clinically insignificant tumors.

Adenocarcinoma↗
PubMed2003

Can prostate specific antigen derivatives and pathological parameters predict significant change in expectant management criteria for prostate cancer?

PURPOSE: A prior report established that pretreatment criteria based on clinical and biopsy pathology parameters can predict men who harbor small volume prostate cancer who might be followed expectantly. However, some of these men will exhibit disease progression with time and will need definitive therapy. To detect those in whom disease may progress, repeat prostate biopsies are performed at yearly intervals. Therefore, we determined whether biomarkers could be used to determine those in whom disease is likely to progress and thus those who require definitive therapy. MATERIALS AND METHODS: Initial and repeat biopsy information along with transrectal ultrasound measurements of gland volume, total prostate specific antigen (PSA), %free PSA (%fPSA) and total PSA velocity were evaluated in 78 men, 45 from the prior study, in whom disease was being managed expectantly. Univariate and multivariate logistic regression analyses determined variables that predicted a favorable tumor burden based on biopsy pathology status at each subsequent repeat biopsy. A Cox proportional hazards model was produced using 67 of 78 evaluable cases having adequate temporal data to predict hazard ratios for conversion from favorable to unfavorable tumor burden status. RESULTS: At time zero for 78 patients %fPSA, total PSA, and gland volume univariately and multivariately differentiated unfavorable and favorable tumor burden groups (p <0.05). The receiver operator characteristic area under the curve (ROC-AUC) was 83%. At the first followup biopsy 17 of 67 (25.4%) men converted to unfavorable tumor burden status. The %fPSA, PSA velocity and gland volume univariately distinguished these 2 groups (p <0.05) with 82% ROC-AUC. At second repeat biopsy 6 of 36 (16.7%) men converted to unfavorable tumor burden status and the ROC-AUC was 76%. Of the 14 men who had a third repeat biopsy all demonstrated favorable tumor burden status. A Cox proportional hazards model stratified the 67 of 78 men into high (48) and low risk (19) groups based on %fPSA at a 20% cutoff (p <0.01). Classification and regression tree analysis using logistic regression multivariately selected variables predicted favorable tumor burden status with an accuracy that ranged from 75% to 84% during our study. CONCLUSIONS: PSA velocity, %fPSA and gland volume information improves the prediction of men undergoing expectant management who are more likely to have small volume disease based on a 12-core biopsy interpretation within the time of our observations. %fPSA proved to be a valuable marker to stratify the 2 risk groups. Therefore, based on these factors it may be possible to consider deferment of repeat prostate biopsy until adverse results are detected. This rational approach to the management of prostate cancer in older men with small volume cancer seems to be a reasonable strategy.

Aged↗
PubMed2003

Incidental small lymphocytic lymphoma/chronic lymphocytic leukemia in pelvic lymph nodes excised at radical prostatectomy.

CONTEXT: Incidental non-Hodgkin lymphoma is often unrecognized at the time of radical prostatectomy in patients with prostate cancer because of nonspecific symptoms and an inconspicuous pathology. The early identification of lymphoma allows optimal long-term management and prevention of significant morbidity. OBJECTIVE: To show the subtlety of pathologic findings in cases of non-Hodgkin lymphoma in pelvic lymph nodes and the need for scrupulous attention to detail for diagnostic accuracy. DESIGN: Histologic and immunohistochemical profiles of 18 consecutive cases of small lymphocytic lymphoma (SLL) incidentally identified in pelvic lymph node dissections were reviewed and compared with 22 cases of benign pelvic lymph node dissections. RESULTS: Malignant nodes were grossly enlarged and averaged 3.2 cm in their greatest dimension. Histologically, 16 of the SLL cases were characterized by diffuse architectural effacement with obliterated sinuses and rare cortical follicles. Twelve of these cases showed evidence of pseudofollicles. Two cases showed an interfollicular growth pattern with occasional small pseudofollicles. In contrast, benign pelvic lymph nodes averaged 1.7 cm in their greatest dimension. Although most were architecturally distorted by fibrosis, all benign nodes were notable for patent sinuses. Immunohistochemistry was diagnostically helpful in several cases with equivocal morphology. All malignant cases had a B-cell phenotype with aberrant coexpression of T-cell-related antigens typical of SLL. CONCLUSION: Incidental low-grade non-Hodgkin lymphoma identified at radical prostatectomy is often overlooked by both the urologist and the pathologist. Although malignant pelvic lymph node dissections frequently lack overt manifestations of lymphoma, attention to subtle morphologic features coupled with lymph node size and immunohistochemical findings should permit diagnostic accuracy.

Aged↗
PubMed2003

Renal cell carcinoma with intratumoral calcium oxalate crystal deposition in patients with acquired cystic disease of the kidney.

We describe 2 cases of renal cell carcinoma arising in acquired cystic disease of the kidney (ACDK) in patients with end-stage renal disease undergoing hemodialysis for more than 5 years and provide a brief review of the complications of ACDK. In both cases, abundant calcium oxalate crystals were observed within the tumors. Histologically, one of the tumors was a conventional (clear cell) renal cell carcinoma. The other tumor was a bilateral papillary renal cell carcinoma. Both tumors were high-grade carcinomas with extensive oncocytic (acidophilic) features. Also noted within the kidneys were cysts with atypical papillary hyperplasia. The clinicopathologic findings along with review of the literature suggest a relationship between tumor growth and calcium oxalate crystal deposition in patients undergoing hemodialysis with ACDK.

Adenocarcinoma, Clear Cell↗
PubMed2002

Validation of a biopsy-based pathologic algorithm for predicting lymph node metastases in patients with clinically localized prostate carcinoma.

BACKGROUND: The authors validated an algorithm for the preoperative prediction of lymph node (LN) metastases in patients with clinically localized prostate carcinoma. The algorithm was applied to sextant biopsy material and radical retropubic prostatectomy (RRP) stage obtained from a cohort of men who were treated at the authors' institution. METHODS: Four hundred forty-three patients underwent systematic sextant biopsy and RRP with staging lymphadenectomy. The original algorithm was based on systematic sextant biopsy data and classified patients into three risk groups for LN metastases based on the biopsy result. If > or = 4 of 6 biopsies contained any Gleason Pattern 4 disease, then the patient was at high risk for LN metastases (45%). Patients with > or = 1 of 6 biopsies with dominant Gleason Pattern 4 disease (excluding high-risk patients) had an intermediate predicted risk (19%) of LN metastases. All other patients had a low predicted risk of LN metastases (2.2%). The authors assed the percentage of patients who were positive and negative for LN metastases and calculated the specificity and negative predictive value in the series when patients were classified according to the original algorithm. RESULTS: Twenty of 443 patients had intraoperative LN metastases. When applied to the current data, the Hamburg algorithm classified 404 patients in the low-risk group, 30 patients in the intermediate-risk group, and 9 patients in the high risk group. The incidence of LN metastases was 2.47% in the low-risk group, 20% in the intermediate-risk group, and 44.4% in the high-risk group. The negative predictive value for the low-risk group was 97.52%, and the specificity was 94.14%. CONCLUSIONS: The Hamburg algorithm proved a valid tool for the prediction of lymphatic spread in this validation study on data from the authors' institution. The algorithm may serve as a tool to select patients who do not need to undergo pelvic lymphadenectomy at the time they undergo RRP, hence reducing morbidity and expense. More importantly, with the increasing numbers of men undergoing treatment options in whom LN dissection is not performed, this validated algorithm provides an important selection basis regarding the appropriateness of a therapy that does not routinely include LN staging.

Algorithms↗
PubMed2002

Evaluation of non-formalin tissue fixation for molecular profiling studies.

Using a general strategy for evaluating clinical tissue specimens, we found that 70% ethanol fixation and paraffin embedding is a useful method for molecular profiling studies. Human prostate and kidney were used as test tissues. The protein content of the samples was analyzed by one-dimensional gel electrophoresis, immunoblot, two-dimensional gel electrophoresis, and layered expression scanning. In each case, the fixed and embedded tissues produced results similar to that obtained from snap-frozen specimens, although the protein quantity was somewhat decreased. Recovery of mRNA was reduced in both quantity and quality in the ethanol-fixed samples, but was superior to that obtained from formalin-fixed samples and sufficient to perform reverse transcription polymerase chain reactions. Recovery of DNA from ethanol-fixed specimens was superior to formalin-fixed samples as determined by one-dimensional gel electrophoresis and polymerase chain reaction. In conclusion, specimens fixed in 70% ethanol and embedded in paraffin produce good histology and permit recovery of DNA, mRNA, and proteins sufficient for several downstream molecular analyses. Complete protocols and additional discussion of relevant issues are available on an accompanying website (http://cgap-mf.nih.gov/).

Actins↗
PubMed2002

Influence of biopsy perineural invasion on long-term biochemical disease-free survival after radical prostatectomy.

OBJECTIVES: To investigate the influence of biopsy perineural invasion (PNI) on long-term prostate-specific antigen recurrence rates, final pathologic stage, and surgical margin status of men treated with radical prostatectomy. Radical prostatectomy offers the best chance for surgical cure when performed for organ-confined disease. However, the histologic identification of PNI on prostate biopsy has been associated with a decreased likelihood of pathologically organ-confined disease. METHODS: Seventy-eight men with histologic evidence of PNI on biopsy underwent radical prostatectomy by a single surgeon between April 1984 and February 1995 and were compared with 78 contemporary matched (biopsy Gleason score, prostate-specific antigen level, clinical stage, age) controls without PNI. Biochemical disease-free survival and pathologic findings were compared. RESULTS: After a mean follow-up of 7.05 +/- 2.2 years and 7.88 +/- 2.7 years (P = 0.04) for patients with biopsy PNI and controls, respectively, no significant difference in the long-term prostate-specific antigen recurrence rates was observed (P = 0.13). The final Gleason score and pathologic staging were also similar in this matched cohort. Although the numbers of neurovascular bundles resected were comparable between the groups, no difference was found in the rate of positive surgical margins identified (13% versus 10%, P = 0.62). CONCLUSIONS: We were unable to show that PNI on needle biopsy influences long-term tumor-free survival.

Analysis of Variance↗
PubMed2002

Complexed prostate-specific antigen as a staging tool for prostate cancer: a prospective study in 420 men.

Over time, the parameters commonly used to predict pathological stage in men with localized prostate cancer have changed, and there is now little stratification in pretreatment prostate-specific antigen (PSA) concentrations, clinical stages, and biopsy Gleason scores. This prospective study evaluated the utility of complexed PSA (cPSA ) for predicting organ-confined disease in a contemporary series of subjects. The age range of the 420 men was 39 to 72 years (58.2 +/- 6 years). Specimens were collected before radical prostatectomy, and total and free PSA (Hybritech Tandem assays, Beckman Access; Beckman Coulter, Inc., Brea, CA) and total and cPSA (Bayer Immuno 1; Bayer Corporation, Tarrytown, NY) were measured. Pathologic stage was determined from the prostatectomy specimen. Of the 420 men, 316 (75%) had organ-confined disease, and 104 (25%) had non-organ-confined disease (20.7% had extraprostatic extension, 2.6% had seminal vesicle involvement, and 1.4% had positive lymph nodes). Prebiopsy Gleason score distribution was as follows: organ-confined organ-confined, 6 (87%) and 7 (10%); non-organ-confined, 6 (66%) and 7 (30%). Of patients with organ-confined disease, 75% had clinical stage T1c disease compared with 56% for non-organ-confined disease. Using univariate logistic regression, the following variables predicted organ-confined disease: biopsy Gleason score, clinical stage, total PSA, percent free PSA, cPSA, percent cPSA (P <0.05). A multivariate model with biopsy Gleason score, clinical stage, and cPSA had a receiver operator characteristic area under the curve of 0.69. Replacing cPSA with total PSA in this model provided similar information. cPSA and total PSA were highly correlated (r = 0.985). In summary, cPSA was equivalent to total PSA in predicting organ-confined disease. Present and future models and nomograms using PSA as an indicator of pathological stage could consider use of cPSA.

Adult↗