Biomedical subjects

T M Wheeler

Publications and source records attributed to T M Wheeler.

At least 55 records · Page 3Linked to original sources

PubMed1999

Postatrophic hyperplasia of the prostate: lack of association with prostate cancer.

Postatrophic hyperplasia (PAH) of the prostate is a non-neoplastic glandular alteration sometimes confused with prostate carcinoma (PCa) histologically. Although atrophy had long been considered a possible precursor lesion for PCa, a theory that has been largely dismissed, the topographical relationship of PAH to PCa has not been studied systematically. Whole mount sections from 272 randomly selected radical prostatectomy (RP) specimens (T1c, 2, 3, N0, 1) and 44 cystoprostatectomy (CP) specimens (28 with incidental PCa) were assessed for the presence, location, and number of foci of PAH, and then were correlated with the presence and location of PCa foci. PAH was identified in 86 (32%) RP and in 12 (27%) CP specimens. The distribution of PAH foci: peripheral zone (91%), transition zone (8%) and central zone (1%), and apex (49%), mid (39%), and base (12%). For RP specimens, 183 foci of PAH showed no atrophy in a mirror image area of the prostate opposite the focus of PAH. Of the foci, 33% showed PCa either within or within 2 millimeters of the focus of PAH. For the mirror image area without PAH, PCa was identified either within or within 2 millimeters of the area in 40% (p = 0.19). The frequency of PAH in CP specimens and its relationship to incidental PCa was not significantly different from that of RP specimens (p = 0.60, chi square). Therefore, PAH is a relatively common lesion, most often seen in the peripheral zone of the apical third of the gland. PAH does not appear to have any association with PCa.

Adenocarcinoma↗

PubMed1999

Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer.

PURPOSE: Although models exist that place patients into discrete groups at various risks for disease recurrence after surgery for prostate cancer, we know of no published work that combines pathologic factors to predict an individual's probability of disease recurrence. Because clinical stage and biopsy Gleason grade only approximate pathologic stage and Gleason grade in the prostatectomy specimen, prediction of prognosis should be more accurate when postoperative information is added to preoperative variables. Therefore, we developed a postoperative nomogram that allows more accurate prediction of probability for disease recurrence for patients who have received radical prostatectomy as treatment for prostate cancer, compared with the preoperative nomogram we previously published. PATIENTS AND METHODS: By Cox proportional hazards regression analysis, we modeled the clinical and pathologic data and disease follow-up for 996 men with clinical stage T1a-T3c NXM0 prostate cancer who were treated with radical prostatectomy by a single surgeon at our institution. Prognostic variables included pretreatment serum prostate-specific antigen level, specimen Gleason sum, prostatic capsular invasion, surgical margin status, seminal vesicle invasion, and lymph node status. Treatment failure was recorded when there was either clinical evidence of disease recurrence, a rising serum prostate-specific antigen level (two measurements of 0.4 ng/mL or greater and rising), or initiation of adjuvant therapy. Validation was performed on this set of men and a separate sample of 322 men from five other surgeons' practices from our institution. RESULTS: Cancer recurrence was noted in 189 of the 996 men, and the recurrence-free group had a median follow-up period of 37 months (range, 1 to 168 months). The 7-year recurrence-free probability for the cohort was 73% (95% confidence interval, 68% to 76%). The predictions from the nomogram appeared to be accurate and discriminating, with a validation sample area under the receiver operating characteristic curve (ie, a comparison of the predicted probability with the actual outcome) of 0.89. CONCLUSION: A postoperative nomogram has been developed that can be used to predict the 7-year probability of disease recurrence among men treated with radical prostatectomy.

Adult↗

PubMed1999

Interposition of sural nerve restores function of cavernous nerves resected during radical prostatectomy.

PURPOSE: The permanent loss of erectile function when both neurovascular bundles are widely resected at radical prostatectomy as well as the successful use of autologous nerve grafts in reconstructive surgery led us to perform bilateral nerve grafts in an effort to restore erectile function in potent patients treated for prostate cancer who underwent radical retropubic prostatectomy and resection of both neurovascular bundles. MATERIALS AND METHODS: Radical retropubic prostatectomy with deliberate resection of both neurovascular bundles was recommended for high grade, locally extensive prostate cancer in 9 select, sexually active men who reported normal erectile function. After the prostate was removed but before vesicourethral anastomosis an autologous sural nerve graft was interposed between the divided ends of the cavernous nerves bilaterally. Erectile function was monitored by patient interview, questionnaire and nocturnal penile tumescence testing after the operation. RESULTS: Four to 5 months postoperatively patients noticed slowly improving spontaneous erections, as manifested by mild tumescence regularly every several hours. Nocturnal penile tumescence testing with the RigiScan device at 4 to 6 months in 2 cases revealed erections that approached minimal criteria for normalcy. Approximately 14 months after surgery a rigid erection sufficient for penetration and intercourse developed in 1 patient. He described this event as "an erection of substance-hard, not just fluffy." CONCLUSIONS: We have developed a technique using sural nerve grafts to restore continuity of the cavernous nerves, which are resected during radical prostatectomy. The early return of spontaneous partial erections in our patients suggests that interposition nerve grafts may enhance the recovery of erectile function when the neurovascular bundles are resected.

Adenocarcinoma↗

PubMed1999

Levels of expression of p27KIP1 protein in human prostate and prostate cancer: an immunohistochemical analysis.

p27KIP1 is a member of the CIP/KIP family of cyclin-dependent kinase inhibitory proteins that negatively regulate cell proliferation. Recent studies reported decreased p27 expression in breast and colon carcinomas and found that the loss of p27 is associated with a poor prognosis. We report here the results of our immunohistochemical analysis of p27 in human prostate cancer. Formalin-fixed, paraffin-embedded, whole-mount sections of prostate cancer from 73 selected patients treated by radical retropubic prostatectomy were obtained from the Department of Pathology, The Methodist Hospital, Houston, Texas. Ten histologically normal and nine high-grade prostatic intraepithelia neoplasia foci were selected from these whole-mount sections, and nine cases of transplant donor prostates were chosen as controls. Also, 10 prostate cancer metastatic lymph nodes were used to compare with the primary cancer group. Sections were immunostained with a monoclonal antibody against p27 protein using the avidin-biotin complex immunohistochemical method. Immunoactivity was evaluated without knowledge of follow-up and recorded as the p27 labeling index (LI) (defined as the percentage of p27-positive cells among epithelia of the same category). The p27 (LI) in normal prostatic epithelia was 86.4+/-3.5% (the mean +/- the standard error of the mean). In contrast, the p27 immunoreactivity was significantly lower in cancers (LI: 43.5 +/-3.7%, P < .001) and in the high-grade prostatic intraepithelial neoplasia group (LI: 59.3 +/- 3.2%, P < .05). Expression of p27 in the metastatic lymph node group was significantly lower than in the other groups, including the prostate cancer cases and the cases of high-grade intraepithelial neoplasia (LI, 7.0%; P = .05). There was no association of the mean p27 LI with progression after radical prostatectomy. Nonrecurrent cases, with a mean follow-up time of greater than 5 years (n = 45), equalled 41.9%; recurrent cases, with a mean follow-up time of 18.3 months (n = 28), equalled 40.0%. The mean p27 LI was not associated with pathologic stage. Organ-confined specimens (n = 21) equalled 34.2%; cases of extraprostatic extension (n = 24) equalled 46.5%; and samples showing seminal vesicle involvement (n = 14) equalled 47.6%. In 14 cases with lymph node metastases, the mean p27 LI was 48.1% in the primary cancer (P = .2322). There was no association of the mean p27 LI with the Gleason score (P = .4747) nor with the clinical stage (P = .9914).

Cell Cycle Proteins↗

PubMed1999

Decreased expression of transforming growth factor beta receptor type I is associated with poor prognosis in bladder transitional cell carcinoma patients.

Transforming growth factor (TGF) beta, a potent growth inhibitor of proliferation in most cells, usually exerts its effects through an interaction with membrane receptors, type I (TbetaR-I) and type II (TbetaR-II). In the present study, the expression of TGF-beta receptors was correlated with tumor grade, pathological stage, and probability of progression and survival in patients with bladder transitional cell carcinoma (TCC). To this end, immunohistochemistry was carried out in specimens obtained from 59 patients who underwent either radical cystectomy or transurethral resection of bladder tumor. Among these patients, 18 (30.5 %) had loss of TbetaR-I expression, whereas 27 (44.0%) had loss of TbetaR-II expression. There was a correlation between the loss of expression of TbetaR-I and TbetaR-II and the tumor grade (P = 0.041 and P = 0.026, respectively). In addition, both pathological and lymph node status also were associated with the loss of TbetaR-I and TbetaR-II expression (P = 0.025 and P = 0.004, respectively). Interestingly though, only the loss of expression of TbetaR-I was associated with an increased probability of tumor progression and a decreased probability of survival (P = 0.0046 and P = 0.0022, respectively). These results suggest that the status of TbetaR-I expression may be a potential prognostic marker in patients with bladder TCC.

Activin Receptors, Type I↗

PubMed1999

Pathological features and prognostic significance of prostate cancer in the apical section determined by whole mount histology.

PURPOSE: We test the hypothesis that cancer in the apical section of the prostate is an important independent factor in predicting the progression of clinically localized prostate cancer. MATERIALS AND METHODS: We analyzed clinical data and whole mount histological step sections for 500 patients who had undergone radical retropubic prostatectomy for clinically localized prostate cancer. RESULTS: Cancer was in the apex of the prostate in 175 patients (35%). These patients had a larger cancer and higher incidence of positive surgical margins, and were more likely to have a poorly differentiated cancer than the 325 patients without cancer in the apex. However, the presence of apical cancer was not a significant predictor of clinical or prostate specific antigen progression in either univariate or multivariate Cox proportional hazards models when analyzed for the entire group or only in patients with tumor confined to the prostate. CONCLUSIONS: Apical cancer in a radical prostatectomy specimen is simply a sign of a larger volume cancer and is not independently associated with an increased risk of clinical or prostate specific antigen progression.

Adult↗

PubMed1998

A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer.

BACKGROUND: Few published studies have combined clinical prognostic factors into risk profiles that can be used to predict the likelihood of recurrence or metastatic progression in patients following treatment of prostate cancer. We developed a nomogram that allows prediction of disease recurrence through use of preoperative clinical factors for patients with clinically localized prostate cancer who are candidates for treatment with a radical prostatectomy. METHODS: By use of Cox proportional hazards regression analysis, we modeled the clinical data and disease follow-up for 983 men with clinically localized prostate cancer whom we intended to treat with a radical prostatectomy. Clinical data included pretreatment serum prostate-specific antigen levels, biopsy Gleason scores, and clinical stage. Treatment failure was recorded when there was clinical evidence of disease recurrence, a rising serum prostate-specific antigen level (two measurements of 0.4 ng/mL or greater and rising), or initiation of adjuvant therapy. Validation was performed on a separate sample of 168 men, also from our institution. RESULTS: Treatment failure (i.e., cancer recurrence) was noted in 196 of the 983 men, and the patients without failure had a median follow-up of 30 months (range, 1-146 months). The 5-year probability of freedom from failure for the cohort was 73% (95% confidence interval = 69%-76%). The predictions from the nomogram appeared accurate and discriminating, with a validation sample area under the receiver operating characteristic curve (i.e., comparison of the predicted probability with the actual outcome) of 0.79. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of treatment failure among men with clinically localized prostate cancer treated with radical prostatectomy.

Adult↗

PubMed1998

Reduced lysyl oxidase messenger RNA levels in experimental and human prostate cancer.

To identify genes associated with prostate cancer progression, we developed a strategy involving the use of differential display PCR and a panel of genetically matched primary tumor- and metastasis-derived mouse prostate cancer cell lines. We analyzed sequences that were differentially stimulated by transforming growth factor-beta1 in primary tumor-versus metastasis-derived cell lines, based on our previous studies indicating that acquisition of differential responses to this growth factor could result in phenotypic traits that facilitate tumor metastasis from specific cell clones within the primary tumor. Using this system, we isolated and sequenced a cDNA fragment that encoded mouse lysyl oxidase (LO) and was induced by transforming growth factor-beta1 in primary tumor but not in metastasis-derived cells. Northern blotting analysis revealed increased LO expression in a panel of primary tumor cell lines but significantly reduced or nondetectable expression in their matched metastatic counterparts. Further in situ hybridization analysis revealed LO expression in normal mouse prostate epithelium but, in most cases, progressive loss of expression in primary prostate cancer and associated metastatic lesions. Importantly, in situ hybridization studies of normal human prostate and prostate malignancies revealed a similar loss of expression during progression to metastasis. The progressive loss of LO expression during prostate cancer progression provides information that may increase our understanding of the mechanisms that underlie this disease. In addition, LO may provide a useful molecular marker and/or establish a novel therapeutic target for prostate cancer.

Animals↗

PubMed1998

Assessment of the biologic markers p53, Ki-67, and apoptotic index as predictive indicators of prostate carcinoma recurrence after surgery.

BACKGROUND: This study was designed to evaluate the potential of the molecular and cellular markers p53, Ki-67, and apoptotic index (AI) as adjuncts to the commonly available variables of tumor grade, clinical stage, and serum prostate specific antigen to predict prostate carcinoma recurrence after radical prostatectomy. METHODS: Representative punch biopsy specimens of prostate carcinoma from whole mount paraffin blocks were evaluated from 47 men who underwent radical prostatectomy. Two groups were defined: those without evidence of prostate carcinoma recurrence after 5 years of follow-up (N = 30) and those with carcinoma recurrence (N = 17). Gleason grade, clustered p53 immunostaining, Ki-67 immunostaining, and AI were determined by standard techniques. RESULTS: All variables tested were associated with disease recurrence by univariate analysis: AI (P = 0.005), clustered p53 immunostaining (P = 0.0070), and Ki-67 immunostaining (P = 0.0390). Using multivariate analyses that included each biomarker with routinely available features, only AI (P = 0.0234) and clustered p53 immunostaining (P = 0.0389) added independent prognostic information (Ki-67 immunostaining, P = 0.1285). In the final logistic regression model that included standard variables with AI and p53, only AI reached statistical significance (P = 0.0332). CONCLUSIONS: The continued assessment of additional biomarkers for prostate carcinoma recurrence is important to identify better those patients who may be candidates for early adjuvant therapy and also to further our understanding of the neoplastic potential of a particular malignancy.

Aged↗

PubMed1998

Quantitative immunohistochemical analysis of insulin-like growth factor binding protein-3 in human prostatic adenocarcinoma: a prognostic study.

PURPOSE: We sought to characterize and quantitate the expression of IGFBP-3 in adenocarcinoma of the prostate and to test whether it correlated with tumor differentiation determined by Gleason grade. We also investigated the potential of using IGFBP-3 as a prognostic indicator of clinically localized prostate cancer. MATERIALS AND METHODS: Initially we evaluated the expression of IGFBP-3 in six normal and twenty neoplastic prostates using standard immunohistochemical techniques (study 1). We then obtained radical prostatectomy specimens from twenty-four patients with a preoperative diagnosis of clinically localized prostate adenocarcinoma and five year follow up information, and nine normal prostates from organ donors or from patients undergoing cystoprostatectomy (study 2). All specimens were immunostained with a polyclonal anti-human IGFBP-3 antibody. A single pathologist reviewed all sections and assigned a Gleason grade to each cancer focus. Using computer-assisted video image analysis, we quantified the intensity of IGFBP-3 immunostaining of each cancer focus and of normal controls. RESULTS: Normal prostatic epithelium showed intense cytoplasmic IGFBP-3 staining. The stromal compartment showed less intense staining, although there were occasional areas with strong immunoreactivity. The cellular distribution of IGFBP-3 staining in prostatic adenocarcinoma was comparable to normal tissue; however, the intensity of detectable staining in neoplastic epithelial cells was significantly decreased. Two foci of prostatic intraepithelial neoplasia (PIN) demonstrated IGFBP-3 immunoreactivity decreased in comparison to normal epithelium, but greater than prostatic adenocarcinoma. Histologically normal epithelium surrounding cancer foci also showed decreased immunostaining for IGFBP-3 compared with normal prostate. The marked decrease in immunostaining intensity of IGFBP-3 in prostate adenocarcinoma was not associated with Gleason grade or with clinical outcome. CONCLUSION: Malignant transformation of prostatic epithelium was associated with a significant decrease in the amount of immunoreactive IGFBP-3 (p <0.0001); however, this parameter did not correlate with Gleason grade of the tumor or with patient outcome. The decrease in immunostaining intensity of IGFBP-3 in all Gleason grades and in PIN suggests that lower expression of IGFBP-3 is an early event in prostatic carcinogenesis. The finding that decreased IGFBP-3 immunostaining did not correlate with clinical outcome suggests that this parameter is not a therapy-guiding prognostic indicator for clinically localized prostate cancer.

Adenocarcinoma↗

PubMed1998

The association of selected pathological features with prostate cancer in a single-needle biopsy accession.

Isolated high-grade prostatic intraepithelial neoplasia (PIN) has been shown to be a positive predictor of prostate cancer (PCa) on follow-up biopsy. However, the incidence of isolated high-grade PIN in needle biopsy specimens has been reported with a highly variable frequency of 1% to 15%. The current study examined the relationship of various pathological features with PCa on a single biopsy accession. A study population of 388 community-based consecutive needle biopsy accessions was prospectively recorded by a single pathologist (T.M.W.). All of the individual biopsy specimens were coded for the presence of PCa, high-grade PIN, low-grade PIN, chronic inflammation (CI), intraluminal prostatic crystalloids (IPC) in benign glands, and mucinous metaplasia (MM). One hundred twenty-nine (33%) of the patients were diagnosed with PCa. The 8% incidence of isolated high-grade PIN was consistent with previous studies. The incidence of other pathological features were as follows: high-grade PIN, 14%; low-grade PIN, 13%; CI, 30%; IPC, 4%; and MM, 8%. Of the patients with high-grade PIN, 47% had PCa on a separate core biopsy, whereas 31% of patients without high-grade PIN were observed to have PCa (P=.021). Of the patients with CI, 21% were found to have PCa on a separate core, whereas 38% of patients without CI were found to have PCa (P=.0009). None of the other pathological features surveyed showed any significant association with PCa. High-grade PIN was a relatively common finding (14%) in this study and was positively associated with PCa on a separate core from the same accession biopsy. The negative association of CP with PCa within the same accession has not been reported previously and may be an artifact related to the clinical indications for a prostatic biopsy.

Adenocarcinoma↗

PubMed1998

Patterns of high-grade prostatic intraepithelial neoplasia associated with clinically aggressive prostate cancer.

High-grade prostatic intraepithelial neoplasia (PIN) is the only widely accepted precursor lesion for prostatic adenocarcinoma (PCa). However, the spread of established PCa within prostatic ducts may be indistinguishable morphologically from high-grade PIN. By convention, all cytologically malignant cellular proliferations within prostatic ducts have been lumped into a PIN category, although there have been recent attempts by McNeal to develop reproducible criteria to separate high-grade PIN from the spread of established PCa within prostatic ducts--intraductal carcinoma (IDCa). Using McNeal's criteria for IDCa, we studied whole-mount sections from 252 patients with pT3NO PCa for the presence of IDCa and correlated the presence or absence of IDCa with Gleason score, total tumor volume, surgical margin status, seminal vesicle involvement, and disease progression. Patients with IDCa had higher Gleason score and total tumor volume and were more likely to show seminal vesicle involvement and disease progression than those patients without IDCa. In addition, IDCa was of independent prognostic significance. Total tumor volume and surgical margin status had no independent prognostic significance in this data set.

Adenocarcinoma↗

PubMed1998

Clinical and pathological significance of the level and extent of capsular invasion in clinical stage T1-2 prostate cancer.

This study was performed to assess the relationship between the level and extent of prostatic capsular invasion (PCI) by cancer and the clinical and pathological features and prognosis of early-stage prostate cancer. We conducted a retrospective analysis of the clinical (age, stage, grade, prostate specific antigen [PSA] level) and pathological (tumor volume, stage, grade, surgical margins) features of 688 patients treated with radical prostatectomy to determine the pathological features and probability of recurrence associated with various levels of PCI. Radical prostatectomy specimens were serially sectioned and examined by whole-mount technique. Progression-free probabilities (PFP) after radical prostatectomy were determined by Kaplan-Meier and Cox proportional hazards regression analysis. Progression was defined as a rising serum PSA < or = 0.4 ng/mL or clinical evidence of recurrent cancer. Increasing clinical stage, Gleason grade in the biopsy specimen, and pretreatment serum PSA levels were each associated with increasing levels of PCI (P < .001). In the radical prostatectomy specimen, increasing levels of PCI were significantly associated with increasing tumor volume (P < .001), Gleason grade (P < .0001), seminal vesicle involvement (SVI, P < .001) and lymph node metastases (+LN, P < .001). None of 138 patients without capsular invasion had SVI or lymph node metastases (+LN), and all remained free of progression, even though some had large volume (up to 6.26 cm3) or poorly differentiated (Gleason sum up to 8) cancers. Invasion into the capsule (n = 271) was occasionally associated with SVI (6%) or +LN (3%) and a significantly (log-rank test) lower PFP of 87% at 5 years. Focal and extensive extraprostatic extension (EPE) were associated with progressively increased risk of SVI and +LN and lower PFP (73% and 42%, respectively). In a multivariate analysis, the level of PCI was an independent prognostic factor (P < .001). There is a strong association between the level of invasion of cancer into or through the prostatic capsule and the volume, grade, pathological stage, and rate of recurrence after radical prostatectomy. Prostate cancer does not appear to metastasize in the absence of invasion into the capsule regardless of the volume or grade of the intracapsular tumor. Subclassification of patients according to the levels of PCI provides valuable prognostic information.

Adenocarcinoma↗

PubMed1998

The significance of intraluminal prostatic crystalloids in benign needle biopsies.

Intraluminal prostatic crystalloids (IPC) are more common in prostate cancer acini than in benign acini. This study was undertaken to evaluate the hypothesis that crystalloids seen in a benign biopsy may indicate an increased risk of a concomitant prostatic carcinoma. A total of 600 patients underwent more than one prostate biopsy. For 394 patients the results of the biopsy were either negative or positive for prostate cancer. After exclusion of patients whose biopsy results were considered negative but coded as high-grade prostatic intraepithelial neoplasia or were suspicious for cancer or whose slides were unavailable for review, 331 patients remained. Biopsy results for these patients were evaluated for the presence of IPC. Also, 18 completely-embedded benign prostates from cystoprostatectomy specimens from patients with bladder cancer were evaluated for the presence of IPC. Seven hundred twenty-five biopsy specimens were reviewed; 51 (7%) contained crystalloids. Thirty-two of 634 (5%) benign biopsy specimens and 19 of 91 (21%) prostatic carcinoma biopsy specimens contained crystalloids. Sixteen of 331 patients (5%) had crystalloids in the initial benign biopsy specimen; 6 patients subsequently were determined to have carcinoma (38%), and 10 continued to have negative results (62%). Three hundred fifteen initial benign biopsies did not show crystalloids; 83 (26%) patients were subsequently diagnosed as having prostatic carcinoma (p = 0.238, Fisher's Exact Test, chi-square test). The IPC were found in 5 of 18 cystoprostatectomy prostates (28%). In this study, the presence of IPC on the initial biopsy specimens was not a significant risk factor for a subsequent diagnosis of prostate cancer. The IPC were not uncommon in prostates without cancer.

Adenocarcinoma↗

PubMed1998

Elastic moduli of breast and prostate tissues under compression.

To evaluate the dynamic range of tissue imaged by elastography, the mechanical behavior of breast and prostate tissue samples subject to compression loading has been investigated. A model for the loading was validated and used to guide the experimental design for data collection. The model allowed the use of small samples that could be considered homogeneous; this assumption was confirmed by histological analysis. The samples were tested at three strain rates to evaluate the viscoelastic nature of the material and determine the validity of modeling the tissue as an elastic material for the strain rates of interest. For loading frequencies above 1 Hz, the storage modulus accounted for over 93 percent of the complex modulus. The data show that breast fat tissue has a constant modulus over the strain range tested while the other tissues have a modulus that is dependent on the strain level. The fibrous tissue samples from the breast were found to be 1 to 2 orders of magnitude stiffer than fat tissue. Normal glandular breast tissue was found to have an elastic modulus similar to that of fat at low strain levels, but the modulus of the glandular tissue increased by an order of magnitude above fat at high strain levels. Carcinomas from the breast were stiffer than the other tissues at the higher strain level; intraductal in situ carcinomas were like fat at the low strain level and much stiffer than glandular tissue at the high strain level. Infiltrating ductal carcinomas were much stiffer than any of the other breast tissues. Normal prostate tissue has a modulus that is lower than the modulus of the prostate cancers tested. Tissue from prostate with benign prostatic hyperplasia (BPH) had modulus values significantly lower than normal tissue. There was a constant but not significant difference in the modulus of tissues taken from the anterior and posterior portions of the gland.

Adult↗

PubMed1998

Distribution and significance of microcalcifications in the neoplastic and nonneoplastic prostate.

OBJECTIVE: To determine the distribution and significance of microcalcifications in histologic sections of the prostate. DESIGN: Retrospective review of all histologic slides of completely embedded prostates from surgical specimens. MATERIALS: Randomly selected material included 266 radical prostatectomy and 10 cystoprostatectomy prostates without prostate cancer. Nonrandomly selected specimens included 26 radical prostatectomy specimens with a Gleason pattern 5 component, 24 cases with collagenous micronodules, and 8 cases previously noted to have microcalcifications within foci of prostate cancer. RESULTS: Four patterns of microcalcifications were noted in association with prostate cancer: (1) dystrophic calcification in the comedo-type necrosis of Gleason pattern 5, (2) intraluminal calcification in cribriform-type Gleason pattern 3 prostate cancer, (3) intraluminal calcification in small acinar adenocarcinoma, and (4) stromal calcification within collagenous micronodules associated with prostate cancer. Microcalcifications were noted in 32% of prostates without cancer; 1.9% of randomly selected prostates demonstrated microcalcifications associated with prostate cancer. CONCLUSIONS: Microcalcifications are less common in association with prostate cancer than with benign prostatic ducts and acini. However, intraluminal microcalcifications associated with an atypical small glandular proliferation should not be taken as unequivocal evidence of a benign process.

Calcinosis↗

PubMed1998

Elevated expression of caveolin is associated with prostate and breast cancer.

To identify genes associated with prostate cancer progression, we developed a strategy involving the use of differential display-PCR with a panel of genetically matched primary tumor- and metastasis-derived mouse prostate cancer cell lines. We isolated a cDNA fragment with homology to the mouse caveolin-1 gene. Northern blotting with this fragment revealed increased caveolin expression in metastasis-derived cell lines relative to primary tumor-derived cell lines. Western blotting with a polyclonal caveolin antibody confirmed increased caveolin protein in metastasis-derived mouse cell lines and expression in three of four human prostate cancer cell lines. Immunohistochemical analysis of a human prostate cancer cell line demonstrated a prominent granular pattern of caveolin accumulation. Subsequent analysis of mouse and human prostate specimens revealed minimal caveolin expression in normal epithelium with abundant staining of smooth muscle and endothelium. The frequency of caveolin-positive cells was increased in prostate cancer with markedly increased accumulation of caveolin and a granular staining pattern in lymph node metastatic deposits. In human breast cancer specimens, increased caveolin staining was detected in intraductal and infiltrating ductal carcinoma as well as nodal disease. Caveolin therefore appears to be associated with human prostate cancer progression and is also present in primary and metastatic human breast cancer.

Animals↗

PubMed1997

Evaluation of a nomogram used to predict the pathologic stage of clinically localized prostate carcinoma.

BACKGROUND: A Nomogram based on pretreatment prostate specific antigen (PSA) level, tumor grade, and clinical stage has recently been developed and distributed to physicians. It was distributed to aid physicians in making treatment recommendations by predicting the probability of the final pathologic stage of clinically localized prostate carcinoma. The Nomogram was based on data for one patient population, and the validity of its application in general urologic practices had not yet been evaluated. METHODS: In the current study, the authors tested the performance of the Nomogram against data from their series of 697 men who underwent radical prostatectomy during the PSA era. Predictions made with the Nomogram were applied to the authors' data set, and the predictions were compared with actual outcomes of the authors' patients. A localized least-squares regression smoothing technique was used to determine whether the Nomogram was calibrated accurately for the authors' data and whether it discriminated across a full spectrum of patient characteristics. RESULTS: Many of the predicted probabilities of the Nomogram were accurate, but some were suboptimal when applied to the authors' data set. Although the Nomogram did discriminate quite well between organ-confined and nonconfined cancer, it had difficulty predicting high probabilities of seminal vesicle invasion and lymph node metastasis, which are the pathologic features with the most profound impact on prognosis. CONCLUSIONS: The Nomogram predicted organ-confined disease accurately. However, because not all of its predictions were completely calibrated when applied to the authors' data set, the authors conclude that the Nomogram may not be totally applicable to general urologic practice until further validation and possible modifications are performed.

Data Interpretation, Statistical↗