Search

We studied the clinical and histologic features of 10 cases of prostatic leiomyoma with atypical bizarre nuclei. Immunohistochemical studies were undertaken in 6 cases. Patient follow-up was obtained in all cases. Patients ranged in age from 50 to 82 years (mean, 65 years) and presented with urinary obstructive symptoms in 7 cases, abnormal digital rectal examination in 3 cases. The histologic findings consisted of a solid circumscribed expansile stromal nodule with abundant smooth muscle and variable numbers of atypical bizarre giant cells. The cells of the tumor displayed intense immunoreactivity for desmin, actin, and androgen receptor and weak to moderate reactivity for vimentin. Four local recurrences were seen, with a follow-up for 3 to 16 years (mean, 7.4 years), but no evidence of sarcomatous transformation occurred. Despite worrisome histologic appearance, a benign clinical behavior was seen in all cases.

OBJECTIVES Contemporary prostate carcinoma is frequently of small volume and early stage. Subtotal gland ablation by minimally invasive therapies such as cryotherapy demands preoperative prediction of unifocal, unilateral, margin-negative, and small volume (less than 0.5 mL) cancer. METHODS We examined matched biopsy and prostatectomy and clinical data from 393 patients at two institutions who underwent surgery in 2000 through 2003. Radical prostatectomy specimens were uniformly sectioned at 5-mm intervals and completely embedded. Numerous clinical and biopsy variables were correlated by regression analysis with unifocal, unilateral, margin-negative, and 0.5 mL or less volume cancer in the prostatectomy specimen. Odds ratios (OR) were determined. RESULTS At prostatectomy, 92 (23%) had unifocal cancer, 90 (23%) had unilateral cancer, 348 (89%) had organ-confined cancer, and 106 (31%) had small volume cancer. Unilateral cancer occurred in 71% to 76% of cases of unilateral cancer in the biopsy (OR, 4.30; if 9 or more cores were sampled, OR rose to 6.83), and was predicted by unifocality in the biopsy (OR, 2.63). Unifocal cancer was predicted by unilateral (OR, 2.66) but not unifocal, cancer present in the biopsy. Negative surgical margins were predicted by unilateral (OR, 2.53; positive predictive value, 82%) cancer in the biopsy and by serum prostate specific antigen (OR, 5.33). Small volume cancer was predicted by unilateral (OR, 5.50) and unifocal (OR, 7.98) cancer in the biopsy; Gleason score greater than 7 predicted a non-small volume cancer (OR, 7.52). CONCLUSIONS Unilateral or unifocal cancer on biopsy are among the strongest predictors of unilateral, unifocal, and small volume prostate cancer in contemporary practice.

High-grade prostatic intraepithelial neoplasia is considered the most likely precursor of prostatic carcinoma. The only method of detection is biopsy; prostatic intraepithelial neoplasia (PIN) does not significantly elevate serum prostate-specific antigen concentration and cannot be detected by ultra-sonography. The incidence of PIN in prostate biopsies averages 9% (range, 4%–16%), representing 115,000 new cases of PIN diagnosed each year in United States. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeated biopsy for concurrent or subsequent invasive carcinoma. Carcinoma will develop in most patients with PIN within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype that are intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.

BACKGROUND As dihydrotestosterone (DHT) is the most potent androgen in the prostate, inhibition of the 5α-reductase isoenzymes, which convert testosterone to DHT, could be an appropriate target for the treatment of prostate cancer. METHODS Eighty-one men with clinically localized prostate cancer received daily dutasteride 3.5 or 0.5 mg, or no therapy for 4 months before radical prostatectomy. Histopathological assessments were conducted on prostatectomy specimens. RESULTS Treatment with dutasteride was associated with reductions in serum and intraprostatic DHT of ≥90%, and a decrease in total prostate and tumor volumes. No effect of dutasteride was noted on Gleason grade. Histopathological effects on benign tissue were similar but less prominent than those seen with androgen ablation, whereas there was no significant difference in cancer histology among the groups. CONCLUSIONS Dutasteride treatment results in similar but less marked changes compared with androgen ablation. Prostate 66: 1674–1685, 2006. © 2006 Wiley-Liss, Inc.

We assessed the performance of the ImmunoCyt immunocytochemical test for detecting bladder cancer recurrence in patients with prior superficial bladder cancers compared with cystoscopic and histological findings.A total of 341 patients with a history of bladder cancer undergoing monitoring were evaluated at 4 sites. The results of cytology and/or ImmunoCyt were analyzed for sensitivity and specificity compared with biopsy confirmed cancer.The overall sensitivity of cytology alone, ImmunoCyt alone and the 2 methods combined was 23%, 81% and 81%, respectively. The specificity of cytology alone, ImmunoCyt alone and of the 2 methods combined was 93%, 75% and 73%, respectively. The immunocytochemical test was more sensitive than cytology for detecting grades 1 and 2, and stages Ta, T1, and T2 urothelial carcinoma, and it was equally sensitive for detecting grade 3 cancers and carcinoma in situ (CIS). The sensitivity of the combined tests for grades 1 to 3/CIS was 79%, 90% and 82%, while for stages Ta, T1, T2+ and CIS it was 83%, 75%, 100% and 100%, respectively. The overall positive and negative predictive values of the combined tests were 37% and 95%, respectively. Importantly the immunocytochemical test could detect 71% of small (less than 1 cm) tumors.ImmunoCyt is a sensitive test for detecting bladder cancer. Because of its high sensitivity for detecting small tumors, even those of low histological grade, and its high negative predictive value, this test may have a role in decreasing the frequency of cystoscopic examinations for monitoring patients with low risk bladder cancer.

Daily supplementation with the essential trace mineral selenium significantly reduced prostate cancer risk in men in the Nutritional Prevention of Cancer Trial. However, the optimal intake of selenium for prostate cancer prevention is unknown. We hypothesized that selenium significantly regulates the extent of genotoxic damage within the aging prostate and that the relationship between dietary selenium intake and DNA damage is non-linear, i.e. more selenium is not necessarily better. To test this hypothesis, we conducted a randomized feeding trial in which 49 elderly beagle dogs (physiologically equivalent to 62-69-year-old men) received nutritionally adequate or supranutritional levels of selenium for 7 months, in order to mimic the range of dietary selenium intake of men in the United States. Our results demonstrate an intriguing U-shaped dose-response relationship between selenium status (toenail selenium concentration) and the extent of DNA damage (alkaline Comet assay) within the prostate. Further, we demonstrate that the concentration of selenium that minimizes DNA damage in the aging dog prostate remarkably parallels the selenium concentration in men that minimizes prostate cancer risk. By studying elderly dogs, the only non-human animal model of spontaneous prostate cancer, we have established a new approach to bridge the gap between laboratory and human studies that can be used to select the appropriate dose of anticancer agents for large-scale human cancer prevention trials. From the U-shaped dose-response, it follows that not all men will necessarily benefit from increasing their selenium intake and that measurement of baseline nutrient status should be required for all individuals in prevention trials to avoid oversupplementation.

Purpose: The incidence of ipsilateral adrenal metastasis in renal cell carcinoma was evaluated in a prospective fashion to understand more fully the natural history of this disease.Materials and Methods: During a 15-month period 128 radical nephrectomies were performed for stages T1 to T3bN0M0 renal cell carcinoma at our institution. Of these specimens 100 adrenal glands were of sufficient integrity to allow for thin sectioning.Results: Among the 100 adrenal glands 4 adrenal lesions were discovered (2 metastatic renal cell carcinomas and 2 benign adrenal lesions). All 4 lesions were identified preoperatively by computerized tomography or magnetic resonance imaging.Conclusions: Our prospective investigation demonstrates that the rate of ipsilateral adrenal metastasis from renal cell carcinoma is approximately 2 percent, and suggests that when the ipsilateral adrenal gland is well visualized and of normal integrity on preoperative magnetic resonance imaging or computerized tomography adrenal sparing...

Purpose: Phyllodes tumor of the prostate is a rare neoplasm of uncertain malignant potential. We studied a large series of phyllodes tumors to define the combination of histological features that are most useful for predicting patient outcome. Materials and Methods: A total of 23 cases were obtained from our collective files from 1973 to 2002, and numerous clinical and pathological features were evaluated. A review of the reported cases of phyllodes tumor of the prostate was done. Results: Patient age was 25 to 86 years (mean 55) and they usually presented with urinary obstructive symptoms and hematuria. The diagnosis was made in 18 tumors by transurethral resection, in 2 by enucleation, in 1 by tumor resection and in 2 by prostatectomy. We analyzed 5 histological features, including cellularity (scale of 1 to 3), cytologic atypia (scale of 1 to 3), the number of mitotic figures per 10 high power fields, the stroma-to-epithelium ratio (low or high) and necrosis (present or absent). This combination of features revealed that 14 cases were low grade phyllodes tumor, 7 were intermediate grade and 2 were high grade with the high grade cases characterized by increased cellularity, severe cytological atypia, more than 5 mitotic figures per 10 high power fields and a high stroma-to-epithelium ratio, indicating stromal overgrowth. Immunohistochemical studies of 8 tumors revealed consistent, intense cytoplasmic immunoreactivity in stromal cells for vimentin and actin, in luminal epithelial cells for prostate specific antigen, prostatic acid phosphatase and broad-spectrum keratin AE1/AE3, and in basal cells for high molecular weight keratin 34β-E12. Recurrence was seen in 7 of 14 low grade tumors (50%) and in 1 patient low grade sarcoma emerged with subsequent distant metastases 14 years after initial diagnosis following 5 recurrences. Recurrence was seen in 6 of 7 intermediate grade tumors and low grade sarcoma emerged with subsequent abdominal wall metastases in 1 patient 11 years after initial diagnosis following 3 recurrences. The phyllodes tumor recurred in each patient with high grade tumors with a time to first recurrence of 6 and 0.2 years, respectively. Distant metastases developed in these 2 patients. Conclusions: Histological grading of prostatic phyllodes tumors is predictive of short-term outcome based on the combination of stromal cellularity, cytological atypia, number of mitotic figures and the stroma-to-epithelium ratio. However, these tumors usually recur after transurethral prostatic resection and they are often locally aggressive with time. The emergence of overt sarcoma and metastatic disease is more frequent than previously recognized. Complete resection at initial diagnosis appears to be indicated.

High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely preinvasive stage of adenocarcinoma, almost two decades after its first formal description. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma. The only method of detection is biopsy; PIN does not significantly elevate serum prostate-specific antigen (PSA) concentration or its derivatives and cannot be detected by current imaging techniques, including ultrasound. Most patients with PIN will develop carcinoma within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype, which are similar to cancer rather than normal prostatic epithelium, indicating impairment of cell differentiation with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.

In an effort to characterize more fully multifocal renal cell carcinoma, 100 radical nephrectomy specimens with localized renal cell carcinoma were analyzed in a prospective fashion. Analysis of each specimen consisted of preoperative computerized tomography or magnetic resonance imaging, standard pathological examination with frozen section and 3 mm. step sectioning under magnification. Multifocal renal cell carcinoma was found in 16 specimens. Multifocal disease was suspected by preoperative imaging in 7 specimens (44%) and confirmed after standard pathological investigation in 10 (63%). Papillary and mixed histological patterns occurred at a significantly increased rate in specimens with multifocal disease (p = 0.011). Other parameters, such as stage, tumor size and volume, histological grade and deoxyribonucleic acid ploidy were evaluated and did not correlate with the presence or extent of multifocality. The number of secondary tumors per specimen varied from 1 to 50 (median 2) and were of hi...

We evaluated the sensitivity and specificity of cytokeratin (CK) 5/6 for distinguishing foci of atrophy from prostatic adenocarcinoma with and without previous hormonal adjuvant therapy and observed the intensity and pattern of staining in mimickers of prostatic adenocarcinoma (basal cell hyperplasia, atypical adenomatous hyperplasia, and tangentially cut high-grade prostatic intraepithelial neoplasia [PIN]). We reviewed 146 acinar proliferations in 81 specimens (radical prostatectomy, previously untreated, 41; radical prostatectomy, following androgen-deprivation therapy, 11; transurethral resection, previously untreated, 29). All benign acinar proliferations stained positively for CK5/6, with immunoreactivity restricted to basal cells. Untreated and androgen-deprived prostatic adenocarcinomas were invariably negative. The pattern of staining was continuous in 79% of the atrophy cases (15/19), and all foci stained with CK5/6. Characteristic double-layer staining in basal cell hyperplasia was observed in 93% of cases (13/14), and foci of high-grade PIN had a characteristic “checkerboard” staining with areas of discontinuity. Foci of atypical adenomatous hyperplasia showed continuous staining, including cauterized acini in 53% of cases (8/15), with a fragmented basal cell layer pattern in 47% of cases (7/15). CK5/6 staining of the basal cells in foci of atrophy is sensitive and specific for excluding prostatic adenocarcinoma with and without androgen-deprivation effect.

We determined patient tolerance and the sequence of histopathological changes of thermal injury and healing of the prostate after treatment with a novel, rapid, high temperature, liquid filled, flexible balloon thermotherapy system.A total of 17 patients scheduled for prostatic surgery received preoperative high temperature water balloon thermotherapy. In 13 patients intraprostatic, urethral and rectal temperatures were continuously monitored and determined using stereotactic thermal mapping with the patient under spinal anesthesia. The remaining 4 patients had lidocaine gel as the only method of pain control. Patient discomfort was recorded at all times during the procedure. After treatment a prostatic stent was left in place until surgery or spontaneous voiding. Serial sections of the resected prostates were evaluated pathologically with mapping.Treatment was well tolerated by all patients. Prostates were enucleated (in 12 patients) or entirely removed (in 5) at a mean of 35 days (range 15 to 173) after thermotherapy. The predominant pathological findings in the early phase were uniform periurethral hemorrhagic necrosis, extensive urothelial denudation and varying degrees of inflammation. The mean radial depth of necrosis (from the urethra to the viable tissue border) was 0.9 cm (range 0.6 to 1.5) involving a mean of 16% of the prostatic adenoma (range 7.8% to 32%). In the late (resolution) phase necrotic tissue had been replaced by scar tissue (fibrosis and hyalinization) with a mean radial depth of 0.13 cm (range 0.01 to 0.24), and the urothelium had largely regrown along the urethra.The fast liquid ablation system for hyperplasia is a new minimally invasive treatment that induces considerable thermal injury to the prostate with uniform necrosis and subsequent sloughing of dead tissue, allowing enlargement of the urethral lumen.

Objectives. Prostate cancer detection in biopsies increases with the number of sites and total tissue sampled. Its dependence on needle core fragment length is uncertain. Methods. We surveyed two consecutive series of sextant needle biopsies from two practices in 1998 to 2000: 251 patients from Pennsylvania (group P) and 1596 from Virginia (group V). We tabulated the gross needle core lengths per sextant site and classified the diagnoses as benign or into four nonbenign categories: high-grade prostatic intraepithelial neoplasia; atypical small acinar proliferation, suspicious; atypical small acinar proliferation, suspicious plus high-grade prostatic intraepithelial neoplasia; and cancer. Logistic regression analysis was used to correlate cancer or a nonbenign diagnosis with the total length (sum of six sites) and, after excluding the sites with more than one core, with the length per single core, and the anatomic site of origin (apex, mid-gland, base). Results. The mean total tissue length sampled was 108 ± 27 mm (range 30 to 275) in group P and 81 ± 22 mm (range 30 to 228) in group V. Sextant sites with a single core contained a mean of 12.8 ± 3.5 mm tissue, with a 3.6-fold variation among the middle 95%. Group V core lengths at the apex averaged 11.8 mm, shorter (P = 0.0001) than mid (13.3 mm) or base (12.7 mm). A predictive value of longer length for a nonbenign diagnosis was noted in four of six sextants (P

There is a marked decrease in the prevalence and extent of high-grade prostatic intraepithelial neoplasia (PIN) in men with prostate cancer after androgen deprivation therapy (ADT) when compared with untreated cases. Basal cell hyperplasia, cytoplasmic clearing, and prominent atrophy of benign acini, with decreased ratio of acini to stroma, accompany this decrease. These findings indicate that the benign and dysplastic prostatic epithelium is androgen dependent. In the normal prostatic epithelium, luminal secretory cells are more sensitive to the absence of androgen than basal cells, and the proliferative cells of high-grade PIN share this androgen sensitivity. The loss of some normal, hyperplastic, and dysplastic epithelial cells with ADT is probably because of acceleration of programmed single-cell death. Remarkably little is known about the comparative effect of different forms of chemical ADT on PIN and cancer, although there appears to be a limited and consistent repertoire of morphologic responses to all forms of this therapy. Conversely, blockade of 5α-reductase with finasteride has little or no effect on PIN (or benign epithelium and cancer), unlike other forms of ADT. A recent international consensus conference sponsored by the World Health Organization concluded that identification of high-grade PIN offered the possibility of chemoprevention with hormonal therapy to block the development of clinical cancer. Multiple chemoprevention trials are planned or under way to address this hypothesis.

BACKGROUND Neuroendocrine (NE) differentiation may be related to the growth and progression of prostate cancer, especially androgen-insensitive tumors. Recently the over-expression of a new anti-apoptosis protein, survivin, has attracted attention for its potential implication in many human cancers. The fact that NE cells in prostate are bcl-2 negative prompted us to investigate if the prostatic NE cells over-express survivin. METHODS Double immunohistochemical staining and immunofluorescence of chromogranin A (CgA) and survivin were performed in 57 patients with localized prostate cancer who underwent radical prostatectomy. The terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method was used for apoptosis detection in three prostate cancer specimens with NE differentiation. The relationship between NE differentiation and clinicopathological characteristics, disease progression as well as patient survival, were analyzed retrospectively. RESULTS It was found that NE cells in both benign and malignant prostate tissues over-expressed the anti-apoptosis protein survivin. While apoptosis was detected in non-NE epithelial cells, all NE cells were negative for apoptosis detection. During the period of follow-up, 17 (63%) of 27 patients with NE differentiation had prostate cancer progression, while 12 (40%) of 30 patients without NE differentiation had systemic prostate cancer progression. 10 (37%) of 27 patients with NE differentiation died from prostate cancer during the period of follow up, while 6 (20%) of 30 patients without NE differentiation died from prostate cancer. However, none of these characteristics reached statistical significance, probably because of the small number of cases enrolled. CONCLUSIONS This study discovers that all the prostatic NE cells express the new anti-apoptosis protein survivin. This provides a strong molecular basis for the hypothesis that NE cells may endure stressful conditions and escape from apoptosis. While our results suggest a trend of NE differentiation with poorer prognosis, the prognosis implication cannot be concluded due to our small sample size. Prostate 48:7–15, 2001. © 2001 Wiley-Liss, Inc.

Activation of the platelet-derived growth factor (PDGF) signaling system has been implicated in the development and malignant progression of diffuse gliomas. Overexpression of PDGF system components, particularly the alpha subtype receptor (PDGFRA), is common in glial tumors, and PDGFRA gene amplification has been reported in glioblastomas. In order to address the incidence of PDGFRA gene amplification in a broad set of diffuse gliomas, we used Southern and fluorescence in situ hybridization (FISH) analyses to examine 167 astrocytic gliomas (20 grade III and 147 grade IV), 41 anaplastic oligodendrogliomas, and 29 anaplastic oligoastrocytomas. PDGFRA gene amplification was identified in 4 anaplastic oligodendrogliomas and in a single case of anaplastic oligoastrocytoma, but in none of the malignant astrocytomas. Each of the 5 tumors with PDGFRA amplification displayed features generally associated with grade IV malignancy in astrocytic tumors. Consequently, our data indicate that this gene alteration is restricted to tumors having oligodendroglial differentiation and highly anaplastic features.

In this review, we discuss the utility of fluorescence in situ hybridization (FISH) in the determination of genetic and chromosomal alterations in prostate cancer specimens. We also discuss the genetic association between prostatic intraepithelial neoplasia (PIN) and adenocarcinoma as detected by FISH and other techniques.FISH is a commonly used technique for the determination of gene and chromosome dosage. In tissue sections, FISH allows precise histopathologic correlation of multiple foci of normal epithelium, premalignant lesions, and carcinoma within a single specimen, including study of intratumoral heterogeneity. PIN and prostatic carcinoma foci have a similar proportion of genetic changes, but foci of carcinoma usually have more alterations. This supports the hypothesis that PIN is the most likely precursor of prostatic carcinoma. The most common genetic alterations in PIN and carcinoma are: (1) gain of chromosome 7, particularly 7q31; (2) loss of 8p and gain of 8q, and (3) loss of 10q, 16q and 18q. Inactivation of tumor suppressor genes and/or overexpression of oncogenes in these regions may be important for the initiation and progression of prostate cancer.FISH is a useful technique to determine genetic relationships between cancer and its precursors. PIN and prostatic carcinoma foci have a similar proportion of genetic alterations, suggesting that PIN is often a precursor of prostatic carcinoma. Genes on chromosomes 7, 8, 10, 16 and 18 may play an important role in both initiation and progression of prostatic carcinoma.

e22203 Background: Dkk-1 is an inhibitor of the canonical Wnt/β-catenin signaling pathway. Inhibition of Wnt pathway results in the stabilization of β-catenin, leading to target gene expression such as cyclin D1, c-myc, VEGF and other factors associated with cell growth. Elevated levels of serum Dkk-1 in a variety of tumor types are well established, and are hypothesized to have a negative prognostic value. Tumor tissue expression of Dkk-1 has not been systematically examined. We evaluated Dkk-1 expression in various tumors. Methods: Utilizing an anonymous banked tumor repository, we identified 119 patient samples (NSCLC (squamous, n=19; adenocarcinoma, n=47), esophageal (squamous, n=15; adenocarcinoma, n=17) and gastric (n=20)). Immunohistochemical (IHC) staining was performed using commercially available antibodies. One pathologist evaluated all slides using IHC staining quantification on a 4-point scale (0, 1+, 2+, 3+). Results: Dkk-1 expression is more pronounced in tumor tissues than peritumoral normal tissues of lung and esophagus. Unexpectedly, Dkk-1 expression is seen in two staining patterns, perinuclear and cytoplasmic that varied by primary location and histology. Conclusions: Elevated Dkk-1 expression is demonstrated in lung, esophageal and gastric cancer regardless of histology. All except squamous cell lung express perinuclear Dkk-1 more frequently than cytoplasmic pattern. Additional studies are needed to understand significance of these patterns and potentially define Dkk-1 as a novel therapeutic target in these malignancies. [Table: see text]

Objectives The purpose of this study was to investigate the toxicity and potential usefulness of transurethral prostatic injection of a collagenase-based solution in treating benign prostatic hyperplasia in dogs. Methods The injected solution contained collagenase, hyaluronidase, Triton X-100 and gentamicin. Twenty-one dogs were randomly divided into three groups for transurethral prostatic needle injection: two treatment groups were observed for 6 and 12 weeks and a control group was observed for 12 weeks. Laboratory studies, clinical monitoring and complete postmortem examination were performed in all animals. Results Gross hematuria was noted in all dogs for a mean of 4 days after injection. No significant postoperative morbidity was noted. There were no significant differences in the values of laboratory tests among the three groups except for a mean increase in serum level of aspartate transaminase for treatment groups on postoperative day 1 ; this resolved by postoperative day 7. Histologically, all treated prostates had stromal atrophy and cystic acinar dilatation involving about 30% of the gland without extraprostatic extension of these changes. The urethra, bladder, rectum, testicles, kidney, liver and lungs were normal and intact in all animals. Conclusions Transurethral injection of this enzyme solution creates a predictable, favorable histologic response in the canine prostate. The procedure appears safe and warrants further investigation for treatment of human benign prostatic hyperplasia.

Objectives. Conflicting findings have been reported regarding the relationship between prostatic intraepithelial neoplasia (PIN) and serum prostate-specific antigen (PSA) concentration. This study evaluates whether high-grade PIN significantly raises serum PSA concentration. Methods. We evaluated 194 totally embedded whole-mounted radical prostatectomy specimens removed for clinically localized prostate cancer. No patient received preoperative therapy. In each specimen, the volume of high-grade PIN and carcinoma was calculated using the grid-counting method. Serum PSA concentration was determined prior to surgery. Cancer volume, gland weight, Gleason score, extraprostatic extension, and PIN volume were then compared according to serum PSA concentration and PSA density. Results. Of the 194 patients, 170 (88%) had high-grade PIN-associated cancer and 24 (12%) had PIN-free cancer within the specimen. PIN volume ranged from 0 to 8.1 cc (mean, 1.3) and cancer volume ranged from 0 to 56.9 cc (mean, 9.1). In a subset of 93 patients with small cancers (less than 6.0 cc), PIN volume ranged from 0 to 6.1 (mean, 0.83) and did not correlate with serum PSA concentration or PSA density ( P = 0.80 and P = 0.69, respectively). In the entire study group, PIN volume did not correlate with PSA density ( P = 0.17), but did correlate with serum PSA concentration ( P = 0.005). Using multiple regression analysis, adjusting for cancer volume, gland weight, Gleason score, and extraprostatic extension, log PIN volume did not contribute to log serum PSA concentration (regression coefficient −0.108; P = 0.51) or log PSA density (regression coefficient −0.104; P = 0.56) in small cancers (less than 6.0 cc). In the entire study group, log PIN volume did not contribute to log serum PSA concentration (regression coefficient −0.182; P = 0.055) or log PSA density (regression coefficient −0.202; P = 0.56). Conclusions. Our data indicate that high-grade PIN does not significantly contribute to serum PSA concentration. We suggest that patients with elevated serum PSA concentration found to have high-grade PIN on transrectal biopsy should not have their elevated serum PSA concentration attributed to high-grade PIN.

Early detection efforts identify prostate cancer at lower clinical and pathologic stages, often resulting in smaller volumes of tumor in radical prostatectomy specimens. In some cases, complete sampling of the radical prostatectomy specimen for biopsy-proven adenocarcinoma reveals minimal or no residual cancer. We evaluated the clinical and pathologic findings in 13 such cases in an effort to document this finding, which we refer to as the "vanishing cancer phenomenon." The mean number of prostate slides examined per case was 79 (range, 34-248). Carcinoma was absent in two cases, present in a single focus in eight cases, and present in two foci in three cases. Mean cancer volume in the 10 cases with residual tumor was 0.019 cc (range, 0.003-0.038); the largest single dimension of any tumor focus was 3 mm. All cancers were well differentiated or moderately differentiated in the biopsy and prostatectomy. Our results indicate that in some cases cancer may be extremely difficult or impossible to find in the prostatectomy specimen despite exhaustive sampling. The incidence of this "vanishing cancer phenomenon" is probably increasing because more low-stage cancers are being treated by prostatectomy. The inability to identify cancer in a prostate removed for needle biopsy-proven carcinoma may not indicate technical failure.

Summary The status of the basement membrane in prostatic intraepithelial neoplasia (PIN) and adenocarcinoma is unsettled. Previous studies using antibodies directed against Type IV collagen have been hindered by intense staining around the stromal smooth muscle fibers, making interpretation of acinar staining difficult. We employed a monoclonal antibody to heparan sulfate proteoglycan (HSPG) to overcome this problem, recognizing that HSPG is present in the basement membrane of epithelial and endothelial cells, but not stromal smooth muscle cells. In 22 totally-embedded whole mount radical prostatectomies for adenocarcinoma which contained PIN, intense HSPG immunoreactivity was observed in the basement membrane of all normal and hyperplastic acini, 98% of acini with high grade PIN, and 100% of acini of well differentiated (Gleason score S) adenocarcinoma; vessels served as the internal positive control, with consistent staining throughout each specimen. The extent of HSPG immunoreactivity in cancer decreased with increasing Gleason grade (measured as percent of acini staining, in 10% increments; p = 0.002). These findings indicate that HSPG is a consistent component of the basement membrane of benign, hyperplastic, and early neoplastic prostatic acini, and, unlike other extracellular matrix proteins such as type IV collagen, is not hindered by background staining around stromal smooth muscle cells. High grade PIN and well differentiated adenocarcinoma usually maintain an intact basement membrane, and loss of the basement membrane occurs with histologic dedifferentiation.

Prostatic atypical adenomatous hyperplasia (AAH) is a small glandular proliferation that has histological similarities with well-differentiated adenocarcinoma. To determine the histochemical profile of AAH, we assessed the production of total neutral mucin, total acidic mucin, and sulfated acidic mucin in 24 cases of AAH, five cases of Gleason primary pattern 1 and 2 adenocarcinoma, and 29 cases of adjacent benign and hyperplastic prostatic tissue. All specimens were formalin-fixed transurethral resections, and the diagnosis in each was confirmed by evaluation of the keratin 34B-E12 immunoreactive basal cell layer (intact in benign and hyperplastic epithelium, fragmented in AAH, and absent in cancer). The extent of mucin staining was measured semiquantitatively in 10% increments according to the number of stained glands. Neutral mucin was found in all but two cases, and there was no apparent difference in the amount of staining in benign glands, AAH, and cancer (mean number of stained glands, 43%). Total acidic mucin was more common in AAH (63% of cases; mean, 11% of glands) and adenocarcinoma (60% of cases; mean, 30% of glands) than in benign glands (0% of cases). Similarly, nonsulfated acidic mucin was more common in AAH (63% of cases; mean, 12% glands) and adenocarcinoma (60% of cases; mean, 8% of glands) than in benign glands (0% of cases); the pattern and intensity of staining for nonsulfated acidic mucin appeared to be similar to that for total acidic mucin in AAH and cancer. These findings indicate that there is a close relationship in mucin expression between AAH and well-differentiated adenocarcinoma. Identification of acidic mucin should be used cautiously as an adjunct in the diagnosis of adenocarcinoma but is useful in separating some cases of AAH and adenocarcinoma from benign prostatic epithelium.

the 10 year follow-up. The cancer-free survival rate after a single cryoablation procedure was 92.2%, this improved to 96.6% after a secondary cryoablation procedure (n = 8). Median preoperative renal mass size was 2.49 cm (range, 0.7cm-8.4cm). In tumors with T1N0M0 (n = 171) disease-free survival (recurrence and death) and recurrencefree survival were significantly different between pT1a and pT1b when stratified by tumor size, 97.5% of mass size 4cm remained disease free up to 10.5 years compared to 71.4% of those with tumor mass size greater than 4cm (Hazard risk ratio 37.5; 95% confidence interval [CI] 3.4 to 414.1; p = 0.003). Recurrence-free survival showed similar pattern between pT1a and pT1b (p = 0.04). Disease-free survival or recurrence-free survival was not significantly modified by gender, age, tumor position, ECOG status, or treatment approach. CONCLUSIONS: Disease-free survival and recurrence-free survival are significantly better in patients undergoing cryoablation for renal neoplasm mass 4 cm or less compared to those with larger tumors. The current T1N0M0 substratification, based on the 2002 TNM criteria, is an effective predictor of the disease-free survival or recurrence-free survival in patients undergoing cryoablation for renal neoplasm.