Biomedical subjects

Shahrokh F Shariat

Publications and source records attributed to Shahrokh F Shariat.

At least 37 records · Page 2Linked to original sources

PubMed2006

Clinical outcomes following radical cystectomy for primary nontransitional cell carcinoma of the bladder compared to transitional cell carcinoma of the bladder.

PURPOSE: The effect of bladder cancer histological subtypes other than transitional cell carcinoma (nonTCC) on clinical outcomes remains uncertain. We conducted a multi-institutional retrospective study of patients with bladder cancer treated with radical cystectomy to assess the impact of nonTCC histology on bladder cancer specific outcomes. MATERIALS AND METHODS: A total of 955 consecutive patients underwent radical cystectomy with bilateral pelvic lymphadenectomy for bladder cancer at 3 academic institutions. TCC was present in the radical cystectomy specimen in 888 patients (93%). NonTCC histology was present in 67 patients (7%), including squamous cell carcinoma in 26, adenocarcinoma in 13, small cell carcinoma in 10 and other nonTCC subtypes (ie spindle cell carcinoma, carcinosarcoma and undifferentiated carcinoma) in 18. For patients alive at last followup median followup was 39 and 23 months for patients with TCC and nonTCC histologies, respectively. Bladder cancer specific progression and survival were assessed using Kaplan-Meier and multivariate Cox proportional hazards analyses. RESULTS: Bladder cancer specific progression and mortality did not differ significantly between patients with SCC and TCC histologies. Patients with nonTCC and nonSCC bladder cancer were at significantly increased risk for progression and death compared to patients with TCC or SCC (p <0.001). This association remained statistically significant in patients with organ confined disease (stage pT2 or lower) and patients with nonorgan confined disease (stage pT3 or higher) (p <0.001). In a multivariate analysis nonTCC and nonSCC histology was associated with an increased risk of bladder cancer progression and death (OR 2.272 and 2.585, respectively, p <0.001), even after adjusting for final pathological stage, lymph node status, lymphovascular invasion and neoadjuvant or adjuvant treatments. CONCLUSIONS: NonTCC and nonSCC histological subtype is an independent predictor of bladder cancer progression and mortality in patients undergoing radical cystectomy for bladder cancer. Patients with bladder TCC and SCC share similar stage specific clinical outcomes.

Aged↗

PubMed2006

Significant upgrading affects a third of men diagnosed with prostate cancer: predictive nomogram and internal validation.

OBJECTIVE: To explore the rate of significant upgrading from biopsy to radical prostatectomy (RP) specimens in a contemporary cohort, and to develop a prognostic model capable of predicting the probability of significant upgrading, as previous reports indicate that up to 43% of men with low-grade prostate cancer at biopsy will be diagnosed with high-grade cancer at RP. PATIENTS AND METHODS: The study cohort comprised 4789 men (median age 63 years, range 39-82) treated with RP, with available clinical stage, prostate-specific antigen levels, biopsy and RP Gleason sum values. These variables were used as predictors in multivariate logistic regression models (LRMs) addressing the rate of significant Gleason sum upgrading, defined as a Gleason sum increase either from < or = 6 to > or = 7 or from 7 to > or = 8 between the biopsy and RP specimens. Regression coefficients were used to develop and validate (200 bootstrap re-samples) a nomogram predicting significant biopsy Gleason sum upgrading. RESULTS: Significant biopsy Gleason sum upgrading was recorded in 1349 (28.2%) patients. In multivariate LRMs, all predictors were highly significant (all P < 0.001). The bootstrap-corrected accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 75.7%. CONCLUSION: Our nomogram might prove highly useful when the possibility of a more aggressive Gleason variant could change the treatment options.

Adult↗

PubMed2005

Pre-operative percent free PSA predicts clinical outcomes in patients treated with radical prostatectomy with total PSA levels below 10 ng/ml.

INTRODUCTION: To evaluate the association of total prostate specific antigen (T-PSA) and percent free PSA (%F-PSA) with prostate cancer outcomes in patients treated with radical prostatectomy (RP). METHODS: Pre-operative serum levels of T-PSA and F-PSA were prospectively measured in 402 consecutive patients treated with RP for clinically localized prostate cancer who had T-PSA levels below 10 ng/ml. RESULTS: T-PSA was not associated with any prostate cancer characteristics or outcomes. Lower %F-PSA was significantly associated with higher percent positive biopsy cores, extracapsular extension, seminal vesicle involvement, lympho-vascular invasion, perineural invasion, positive surgical margins, and higher pathologic Gleason sum. When adjusted for the effects of standard pre-operative features, lower %F-PSA significantly predicted non-organ confined disease, seminal vesicle involvement, lympho-vascular invasion, and biochemical progression. %F-PSA did not retain its association with biochemical progression after adjusting for the effects of standard post-operative features. Based on data from 22 patients with biochemical progression, lower %F-PSA was correlated with shorter T-PSA doubling time after biochemical progression (rho = 0.681, p = 0.010). %F-PSA was lower in patients who failed salvage radiation therapy (p = 0.031) and in patients who developed distant cancer metastases compared to patients who did not (p < 0.001). CONCLUSIONS: Pre-operative T-PSA is not associated with prostate cancer outcomes after RP when levels are below 10 ng/ml. In contrast, pre-operative %F-PSA is associated with adverse pathologic features, biochemical progression, and features of aggressive disease progression in patients treated with RP and T-PSA levels below 10 ng/ml. %F-PSA may improve pre-operative predictive models for predicting clinical outcomes of patients diagnosed with prostate cancer nowadays.

Adult↗

PubMed2005

Pilot study of radiofrequency interstitial tumor ablation (RITA) for the treatment of radio-recurrent prostate cancer.

BACKGROUND: To prospectively evaluate the feasibility, safety, morbidity, and preliminary efficacy of radiofrequency interstitial tumor ablation (RITA) for the focal treatment of patients with local prostate cancer recurrence. METHODS: Eleven patients with biopsy-proven, hormone-naïve, clinically localized prostate cancer were enrolled in a prospective phase I/II trial. Eight patients had failed prior radiation therapy and three were not candidates for curative primary therapy (median Gleason score 7 and 6, respectively). Median follow-up was 20 months. All patients were treated with RITA in an office setting, under intravenous sedation and were discharged after the procedure. Radiofrequency energy was applied via needles placed transperineally under transrectal ultrasound guidance. RESULTS: The placement of 1/4 lesions was aborted in two patients due to increasing rectal temperature. Complications included transient macrohematuria (19%), bladder spasms (9%), and dysuria (9%). Serum PSA levels decreased after RITA >50% in 90% of patients, > 70% in 72% of patients, and > 80% in 46% of patients. The mean PSA doubling time after RITA was slower than that before RITA (37 +/- 22 months vs. 14 +/- 13 months, P = 0.008). At 12 months after RITA, 50% of patients with sufficient follow-up had no residual cancer on repeat systematic 12-core biopsy cores and 67% were cancer-free in biopsy cores sampled from the RITA-treated areas. CONCLUSIONS: RITA treatment is a minimal invasive, rapid, user-friendly, office-based procedure that is well tolerated. Focal ablation with RITA results in effective local disease control in patients with non-metastatic prostate cancer recurrence. Larger, prospective, multicenter clinical studies are needed to confirm these findings.

Aged↗

PubMed2005

Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy.

PURPOSE: We hypothesized that bladder cancer patients with associated lymphovascular invasion (LVI) are at increased risk of occult metastases. METHODS: A multi-institutional group (University of Texas Southwestern [Dallas, TX], Baylor College of Medicine [Houston, TX], Johns Hopkins University [Baltimore, MD]) carried out a retrospective study of 958 patients who underwent cystectomy for bladder cancer between 1984 and 2003. Of patients with transitional-cell carcinoma (n = 776), LVI status was available for 750. LVI was defined as the presence of tumor cells within an endothelium-lined space. RESULTS: LVI was present in 36.4% (273 of 750) overall, involving 26% (151 of 581) and 72% (122 of 169) of node-negative and node-positive patients, respectively. Prevalence of LVI increased with higher pathologic stage (9.0%, 23%, 60%, and 78%, for T1, T2, T3, and T4, respectively; P < .001). Using multivariate Cox regression analyses including age, stage, grade, and number of pelvic lymph nodes removed, LVI was an independent predictor of local (HR = 2.03, P = .049), distant (HR = 2.60, P = .0011), and overall (HR = 2.02, P = .0003) recurrence in node-negative patients. LVI was an independent predictor of overall (HR = 1.84, P = .0002) and cause-specific (HR = 2.07, P = .0012) survival in node-negative patients. LVI maintained its independent predictor status in competing risks regression models (P = .013), where other-cause mortality was considered as a competing risk. LVI was not a predictor of recurrence or survival in node-positive patients. CONCLUSION: LVI is an independent predictor of recurrence and decreased cause-specific and overall survival in patients who undergo cystectomy for invasive bladder cancer and are node-negative. These patients represent a high risk group that may benefit from integrated therapy with cystectomy and perioperative systemic chemotherapy.

Age Distribution↗

PubMed2005

Urinary levels of soluble e-cadherin in the detection of transitional cell carcinoma of the urinary bladder.

OBJECTIVE: To test the hypothesis that elevated urinary levels of soluble E-cadherin (sE-cadherin) would aid in the detection of transitional cell carcinoma (TCC) of the urinary bladder. METHODS: We performed sE-cadherin staining of one murine (MBT2) and four human (RT4, 5637, T24, and TCCSUP) bladder cancer cell lines. sE-cadherin levels were also determined in voided urine of 188 consecutive subjects at risk for TCC recurrence, 31 patients with other uro-pathologic conditions, and 10 healthy subjects using a commercially-available ELISA kit. sE-cadherin was analyzed continuously and categorically on the basis of its median distribution. RESULTS: Moderately and poorly differentiated bladder cancer cell lines had decreased cellular E-cadherin expression, whereas RT4, a well differentiated cell line, had preserved expression. All cell lines had measurable sE-cadherin levels in their conditioned media. The area under the ROC curve of sE-cadherin for the detection of TCC was 0.719 (95%CI, 0.637-0.801; p<0.001). Higher levels of sE-cadherin were associated with positive cytology results (p=0.012) and muscle invasive tumor stage (p=0.009). Urinary sE-cadherin was more sensitive, but less specific than urinary cytology for the detection of bladder TCC. In a multivariable logistic regression analysis, higher sE-cadherin and positive cytology were both associated with an increased risk of bladder TCC (p=0.048 and p<0.001, respectively). Combination of cytology and sE-cadherin allowed categorization of patients into three significantly different risk groups for bladder cancer. Adjustment of sE-cadherin for urinary creatinine levels did not affect any of the outcomes. CONCLUSIONS: Urinary level of sE-cadherin may add information to cytology in the detection of bladder TCC.

Adult↗

PubMed2005

Urinary levels of tumor-associated trypsin inhibitor (TATI) in the detection of transitional cell carcinoma of the urinary bladder.

OBJECTIVE: To assess whether urinary levels of tumor-associated trypsin inhibitor (TATI) would aid in the detection of bladder transitional cell carcinoma (TCC); and to compare diagnostic performance of urinary TATI with that of nuclear matrix protein 22 (NMP22) and barbotage cytology. METHODS: We determined TATI and NMP22 levels in voided urine from 181 subjects: 153 with previous bladder cancer, 20 with urologic pathology other than bladder cancer, and eight healthy volunteers. TATI was analyzed continuously and categorically on the basis of its quartile distribution. We also measured urinary creatinine and barbotage cytology in 173 and 154 patients, respectively. RESULTS: Urinary TATI levels were significantly higher in TCC patients with evidence of tumor on cystoscopic evaluation (n = 96) than in control subjects (n = 85; p < 0.001). Higher levels of TATI were associated with positive cytology assay results (p = 0.018), higher NMP22 levels (p < 0.001), and invasive tumor stage (p = 0.026). The area under the receiver operating characteristics (ROC) curve (AUC) of TATI for the detection of TCC was 0.712 (95%CI: 0.637-0.786). The overall AUCs for TATI and NMP22 were not statistically different from each other (p = 0.174). In the >75% sensitivity region of the ROC curves, TATI was consistently more specific than NMP22. TATI, NMP22, and cytology were independently associated with bladder cancer (p = 0.049, p = 0.040, and p < 0.001, respectively). Adjustment of TATI for urinary creatinine levels did not affect any of the outcomes. CONCLUSIONS: Urinary level of TATI may add independent information to urinary cytology and NMP22 in the detection of bladder TCC. TATI seems to outperform NMP22 for bladder TCC detection.

Adult↗

PubMed2005

Reliability of remembered International Index of Erectile Function domain scores in men with localized prostate cancer.

OBJECTIVES: To test the reliability of recollected International Index of Erectile Function (IIEF) domain scores before and after radical prostatectomy. Recall reliability can be affected by several biases. In men with localized prostate cancer (PCa), conflicting results have been reported. METHODS: Thirty-nine men, aged 44 to 69 years, were invited to participate in a prospectively administered IIEF questionnaire. The survey was administered before and 6 and 12 months after radical prostatectomy. Several months later, a recall IIEF survey targeted the prospectively gathered IIEF data. The independent sample t test, Pearson correlation coefficient, partial correlation, and intraclass correlation coefficient tested the reliability of the recalled IIEF scores versus the prospective ratings. RESULTS: All 39 men completed the prospective and recalled IIEF surveys addressing preoperative erectile function. Surveys targeting function at 6 and 12 months after surgery were completed by 85% and 51% of the participants, respectively. The erectile function domain demonstrated the greatest recall reliability (intraclass correlation coefficient 0.65 to 0.73). Erectile function and sexual desire scale recall reliability was greatest for pretreatment function or function 12 months after surgery. The orgasmic function domain had the lowest recall reliability (intraclass correlation coefficient 0.37 to 0.54). CONCLUSIONS: When restricted to before surgery and 12 months after surgery, most IIEF domains may be reliably used in a retrospective fashion. The erectile function and sexual desire domains appear to be most reliable, possibly because they address more objective areas of men's sexual function.

Adenocarcinoma↗

PubMed2005

Loss of coxsackie and adenovirus receptor expression is associated with features of aggressive bladder cancer.

OBJECTIVES: To examine whether loss of coxsackie and adenovirus receptor (CAR) expression is associated with bladder cancer characteristics and clinical outcomes and with expression of p53 and E-cadherin. Low levels of CAR are associated with decreased efficiency of adenovirus-mediated gene transduction of bladder transitional cell carcinoma. METHODS: Immunohistochemical staining for CAR and p53 was carried out on tissue microarrays from 62 patients who had undergone radical cystectomy. We also examined 30 specimens for E-cadherin expression. RESULTS: CAR expression was lost in 17 (27%) of 62 tumors. Loss of CAR expression was associated with metastases to regional lymph nodes (P = 0.049), muscle-invasive disease (P = 0.025), grade 3 disease (P = 0.038), altered p53 status (P = 0.041), and loss of E-cadherin expression (P = 0.042). With a median follow-up of 60 months, loss of CAR expression was associated with decreased bladder cancer-specific survival (P = 0.029) but not disease progression. When adjusted for the effects of standard pathologic features, only lymph node metastasis was associated with bladder transitional cell carcinoma progression and mortality. CONCLUSIONS: Loss of CAR expression is associated with established markers of biologically aggressive bladder transitional cell carcinoma. The association of CAR with E-cadherin and p53 suggests a potential role for CAR in the regulation of urothelium integrity and the cell cycle.

Aged↗

PubMed2005

Gastrointestinal hemorrhage as first manifestation of metastatic testicular tumor.

We report a case of a man with a testicular mixed germ cell tumor in whom the first symptom was severe anemia secondary to upper gastrointestinal bleeding from a metastatic pure choriocarcinoma. He underwent ileal enterectomy, radical orchiectomy, and several cycles of chemotherapy (cisplatin, etoposide, and bleomycin). He died within 41 days of diagnosis.

Choriocarcinoma↗

PubMed2005

Nomograms including nuclear matrix protein 22 for prediction of disease recurrence and progression in patients with Ta, T1 or CIS transitional cell carcinoma of the bladder.

PURPOSE: We developed and validated nomograms that accurately predict disease recurrence and progression in patients with Ta, T1, or CIS transitional cell carcinoma (TCC) of the bladder using a large international cohort. METHODS: Univariate and multivariate logistic regression models targeted histologically confirmed disease recurrence, and focused on 2,542 patients with bladder TCC from 10 participating centers. Variables consisted of pre-cystoscopy voided urine Nuclear Matrix Protein 22 (NMP22) assay, urine cytology, age and gender. Resulting nomograms were internally validated with bootstrapping. Nomogram performance was explored graphically with Loess smoothing plots. RESULTS: Overall 957 patients had recurrent TCC. Tumor grade and stage was available for 898 patients, including 24% grade I, 43% grade II, and 33% grade III; 45% stage Ta, 32% T1 and/or CIS, and 23% T2 or greater. Bootstrap corrected predictive accuracy for any TCC recurrence was 0.842; grade III Ta/T1 or CIS was 0.869; and T2 or higher stage TCC of any grade was 0.858. Virtually perfect performance characteristics were observed for the nomograms predicting any TCC recurrence or grade III Ta/T1 or CIS. The nomogram predicting T2 or higher stage TCC overestimated the observed probability for predicted values greater than 45%. CONCLUSIONS: We developed and internally validated nomograms that incorporate urinary NMP22, cytology, age and gender to predict with high accuracy the probability of disease recurrence and progression in patients with Ta, T1, and/or CIS bladder TCC. These nomograms could provide a means for individualizing followup in patients with Ta, T1, CIS bladder TCC.

Adolescent↗

PubMed2005

Expression of survivin and apoptotic biomarkers in benign prostatic hyperplasia.

PURPOSE: We assessed the differential expression of survivin and other apoptotic markers in stromal and epithelial compartments of benign prostatic hyperplasia (BPH) and normal prostate tissue. MATERIALS AND METHODS: Immunohistochemical staining for survivin, and transforming growth factor-beta1 and its receptors was done in normal prostate and BPH areas from 114 consecutive patients who underwent radical prostatectomy. Moreover, staining for survivin, Bcl-2, Bax, caspase-3 and Ki-67 was performed in prostate specimens from 23 consecutive patients who underwent open prostatectomy and 4 young patients who underwent cystoprostatectomy and had a normal prostate. RESULTS: Survivin and Bcl-2 expression increased incrementally from normal prostate to epithelial BPH to stromal BPH. Caspase-3 expression was higher in BPH epithelium than in BPH stroma, which in turn was higher than that in normal prostate. Ki-67 was significantly over expressed in BPH stroma and epithelium. Survivin expression in BPH tissue correlated with International Prostate Symptom Score, quality of life, post-void residual urine volume, maximum urine flow rate and transforming growth factor-beta1 expression. CONCLUSIONS: Survivin is over expressed in BPH and it correlates with BPH parameters. Increases in proliferation and inhibition of apoptosis have a role in BPH.

Adult↗

PubMed2005

Anomalies of the wolffian duct derivatives encountered at radical prostatectomy.

Abnormalities of wolffian duct derivatives are usually encountered in young subjects. We identified 4 instances of embryologic malformations of these structures in patients who underwent radical prostatectomy (RP). The first patient had unilateral renal agenesis and a seminal vesicle cyst identified preoperatively by computed tomography. The seminal vesicle cyst was removed during RP. The second patient had renal agenesis and an ectopic ureter entering the right seminal vesicle. These were treated with ureterectomy during RP. The third patient had unilateral duplication of the vas deferens of no clinical consequence. Finally, the fourth patient had left-sided absence of both the vas deferens and seminal vesicle. The anatomy of the lower pelvis is most accurately shown on magnetic resonance imaging. Lower urinary tract malformations are an uncommon occurrence in males. Surgeons who perform numerous RPs will, however, find additional urologic pathologies during RP that may require consideration and tailored management.

Journal Article↗

PubMed2004

Association of preoperative plasma levels of vascular endothelial growth factor and soluble vascular cell adhesion molecule-1 with lymph node status and biochemical progression after radical prostatectomy.

PURPOSE: Angiogenesis is a critical process for cancer progression. We tested whether elevated circulating levels of the angiogenesis-related markers vascular endothelial growth factor (VEGF) and/or soluble vascular cell adhesion molecule-1 (sVCAM-1) are associated with prostate cancer diagnosis, stage, progression, and metastasis. PATIENTS AND METHODS: Plasma levels of VEGF and sVCAM-1 were measured on frozen, archival plasma obtained preoperatively from 215 consecutive patients who underwent radical prostatectomy for clinically localized disease, nine men with untreated prostate cancer metastatic to bones, and 40 healthy men without cancer. RESULTS: Plasma levels of both VEGF and sVCAM-1 were highest in patients with bone metastases (P <.001). VEGF levels were higher in patients with clinically localized disease than in healthy controls (P <.001). VEGF levels were elevated in patients with biopsy and final Gleason sum > or = 7 (P =.036 and P =.020, respectively) and extraprostatic extension (P =.047). Higher preoperative VEGF was independently associated with metastases to lymph nodes (P <.001). Both VEGF and sVCAM-1 were independently associated with biochemical progression after adjustment for the effects of standard preoperative features (P =.014 and P =.039, respectively). VEGF remained independently associated with biochemical progression after adjustment for standard postoperative features (P =.019). CONCLUSION: Plasma levels of VEGF increased incrementally from healthy controls to patients with clinically localized disease to patients with lymph node and skeletal metastases. Higher preoperative VEGF was independently associated with metastases to lymph nodes and biochemical progression after surgery in both pre- and postoperative models. Plasma sVCAM-1 was elevated in men with bone metastases and was associated with biochemical progression in a preoperative model.

Adult↗

PubMed2004

Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy.

CONTEXT: Salvage radiotherapy may potentially cure patients with disease recurrence after radical prostatectomy, but previous evidence has suggested that it is ineffective in patients at the highest risk of metastatic disease progression. OBJECTIVE: To delineate patients who may benefit from salvage radiotherapy for prostate cancer recurrence by identifying variables associated with a durable response. DESIGN, SETTING, AND PATIENTS: Retrospective review of a cohort of 501 patients at 5 US academic tertiary referral centers who received salvage radiotherapy between June 1987 and November 2002 for detectable and increasing prostate-specific antigen (PSA) levels after radical prostatectomy. MAIN OUTCOME MEASURE: Disease progression after salvage radiotherapy, defined as a serum PSA value > or =0.1 ng/mL above the postradiotherapy PSA nadir confirmed by a second PSA measurement that was higher than the first by any amount, by a continued increase in PSA level after treatment, or by the initiation of androgen deprivation therapy after treatment. RESULTS: Over a median follow-up of 45 months, 250 patients (50%) experienced disease progression after treatment, 49 (10%) developed distant metastases, 20 (4%) died from prostate cancer, and 21 (4%) died from other or unknown causes. The 4-year progression-free probability (PFP) was 45% (95% confidence interval [CI], 40%-50%). By multivariable analysis, predictors of progression were Gleason score of 8 to 10 (hazard ratio [HR], 2.6; 95% CI, 1.7-4.1; P<.001), preradiotherapy PSA level greater than 2.0 ng/mL (HR, 2.3; 95% CI, 1.7-3.2; P<.001), negative surgical margins (HR, 1.9; 95% CI, 1.4-2.5; P<.001), PSA doubling time (PSADT) of 10 months or less (HR, 1.7; 95% CI, 1.2-2.2; P =.001), and seminal vesicle invasion (HR, 1.4; 95% CI, 1.1-1.9; P =.02). Patients with no adverse features had a 4-year PFP of 77% (95% CI, 64%-91%). When treatment was given for early recurrence (PSA level < or =2.0 ng/mL), patients with Gleason scores of 4 to 7 and a rapid PSADT had a 4-year PFP of 64% (95% CI, 51%-76%) and of 22% (95% CI, 6%-38%) when the surgical margins were positive and negative, respectively. Patients with Gleason scores of 8 to 10, positive margins, and receiving early salvage radiotherapy had a 4-year PFP of 81% (95% CI, 57%-100%) when the PSADT was longer than 10 months and of 37% (95% CI, 16%-58%) when the PSADT was 10 months or less. CONCLUSIONS: Gleason score, preradiotherapy PSA level, surgical margins, PSADT, and seminal vesicle invasion are prognostic variables for a durable response to salvage radiotherapy. Selected patients with high-grade disease and/or a rapid PSADT who were previously thought to be destined to develop progressive metastatic disease may achieve a durable response to salvage radiotherapy.

Adult↗

PubMed2004

Association of pre- and postoperative plasma levels of transforming growth factor beta(1) and interleukin 6 and its soluble receptor with prostate cancer progression.

PURPOSE: We have shown that preoperative plasma levels of transforming growth factor-beta(1) (TGF-beta(1)), interleukin 6 (IL)-6, and its receptor (IL-6sR) are associated with prostate cancer progression and metastasis. The objectives of this study were to confirm these findings and to examine the association of changes in plasma levels of these markers after surgery with disease progression in a large consecutive cohort of patients. EXPERIMENTAL DESIGN: Plasma levels of TGF-beta(1), IL-6, and IL-6sR were measured pre- and postoperatively (6-8 weeks after surgery) in 302 consecutive patients who underwent radical prostatectomy for clinically localized disease. RESULTS: Pre- and postoperative levels of TGF-beta(1) were significantly elevated in patients with extraprostatic extension, seminal vesicle involvement, and metastases to lymph nodes. In contrast, preoperative levels of IL-6 and IL-6sR, but not postoperative levels, were significantly associated with tumor volume, prostatectomy Gleason sum, and metastases to lymph nodes. In a postoperative model that included pre- and postoperative TGF-beta(1), IL-6, and IL-6sR and standard postoperative parameters, postoperative TGF-beta(1) and prostatectomy Gleason sum were significant predictors of overall and aggressive disease progression. Although, for all patients, plasma levels of all three markers declined significantly after prostate removal, for patients that experienced disease progression, only IL-6 and IL-6sR levels decreased significantly. CONCLUSIONS: For patients undergoing radical prostatectomy, preoperative plasma levels of TGF-beta(1) and IL-6sR are associated with metastases to regional lymph nodes, presumed occult metastases at the time of primary treatment, and disease progression. After prostate removal, postoperative TGF-beta(1) level increases in value over preoperative levels for the prediction of disease progression.

DNA, Neoplasm↗

PubMed2004

p53, p21, pRB, and p16 expression predict clinical outcome in cystectomy with bladder cancer.

PURPOSE: To determine whether p53, p21, pRB, and/or p16 expression is associated with bladder cancer stage, progression, and prognosis. PATIENTS AND METHODS: Immunohistochemical staining for p53, p21, pRB, and p16 was carried out on serial sections from archival specimens of 80 patients who underwent bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer (median follow-up, 101 months). RESULTS: p53, p21, and pRB or p16 expression was altered in 45 (56%), 39 (49%), and 43 (54%) tumors, respectively. Sixty-six patients (83%) had at least one marker altered, and 21 patients (26%) had all three altered. Abnormal expressions of p53, p21, and pRB/p16 expression were associated with muscle-invasive disease (P=.007, P=.003, and P=.003, respectively). The alteration of each marker was independently associated with disease progression (P< or =.038) and disease-specific survival (P< or =.039). In multivariable models that included standard pathologic features and p53 with p21 or p53 with pRB/p16, only p53 and lymph node metastases were associated with bladder cancer progression (P< or =.026) and death (P< or =.028). In models that included p21 and pRB/p16, only p21 and lymph node metastases were associated with bladder cancer progression (P< or =.022) and death (P< or =.028). In a model that included the combined variables p53/p21 and pRB/p16, only p53/p21 and lymph node status were associated with bladder cancer progression (P< or =.047) and death (P< or =.036). The incremental number of altered markers was independently associated with an increased risk of bladder cancer progression (P=.005) and mortality (P=.007). CONCLUSION: Although altered expression of each of the four cell cycle regulators is associated with bladder cancer outcome in patients undergoing radical cystectomy, p53 is the strongest predictor, followed by p21, suggesting a more pivotal role of the p53/p21 pathway in bladder cancer progression.

Adult↗

PubMed2004

Survivin expression is associated with features of biologically aggressive prostate carcinoma.

BACKGROUND: Survivin counteracts cell death and controls mitotic progression. The objectives of the current study were to compare the expression patterns of survivin in normal prostate, primary prostate carcinoma, and lymph node tissues involved with prostate carcinoma and to determine whether the expression of survivin is associated with prostate carcinoma characteristics and progression. METHODS: Immunohistochemical staining for survivin and for transforming growth factor beta1 (TGF-beta1) and its receptors (types I and II; TGF-betaR1 and TGF-betaR2, respectively) was carried out on archival specimens from 114 consecutive patients who underwent radical prostatectomy (median follow-up, 64.8 months). Punch biopsies of the index carcinoma and normal tissue from each specimen were sectioned onto a single slide and stained. The authors also evaluated the expression of survivin in normal and malignant lymph node tissue from eight patients. RESULTS: Survivin was expressed in 41 of 114 normal prostate specimens (36%) from prostates that contained carcinoma, in 81 of 114 primary prostate carcinoma specimens (71%), in 3 of 8 normal lymphoid specimens (38%), and in 7 of 8 prostate carcinoma lymphoid specimens (88%). Survivin expression was associated with higher final Gleason sum (P = 0.001), loss of TGF-betaR1 and TGF-betaR2 expression (P = 0.041 and P = 0.008, respectively), and an increased risk of biochemical progression on univariate analysis (P = 0.0441). Among patients who had disease progression, survivin was expressed more commonly in those who had tumors with features of aggressive behavior. CONCLUSIONS: The expression of survivin gradually increased from normal prostate tissue, to low-grade primary carcinoma, to high-grade primary carcinoma and was highest in lymph node metastases. Survivin expression was associated further with alteration of the TGF-beta pathway and with overall and aggressive biochemical progression after radical prostatectomy.

Adult↗