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Chin-Lee Wu,
Brock E Schroeder,
Xiao-Jun Ma,
Christopher J Cutie,
Shulin Wu,
Ranelle Salunga,
Yi Zhang,
Michael W Kattan,
Catherine A Schnabel,
Mark G Erlander, W Scott McDougal
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ABSTRACT: The accurate determination of the risk of cancer recurrence is an important unmet need in the management of prostate cancer. Patients and physicians must weigh the benefits of currently available therapies against the potential morbidity of these treatments. Herein we describe the development of a gene expression-based continuous risk index and a validation of this test in an independent, blinded cohort of post-radical prostatectomy (RP) patients. A gene expression signature, prognostic for prostate-specific antigen (PSA) recurrence, was identified through a bioinformatic analysis of the expression of 1,536 genes in malignant prostate tissue from a training cohort of consecutive patients treated with RP. The assay was transferred to a real-time RT-PCR platform, and a continuous risk index model was constructed based on the expression of 32 genes. This 32-gene risk index model was validated in an independent, blinded cohort of 270 RP patients. In multivariate analyses, the risk index was prognostic for risk of PSA recurrence and had added value over standard prognostic markers such as Gleason score, pathologic tumor stage, surgical margin status, and presurgery PSA (hazard ratio, 4.05; 95% confidence interval, 1.50-10.94; P = 0.0057). Furthermore, RP patients could be stratified based on the risk of PSA recurrence and the development of metastatic disease. The 32-gene signature identified here is a robust prognostic marker for disease recurrence. This assay may aid in postoperative treatment selection and has the potential to impact decision making at the biopsy stage.
Proceedings of the National Academy of Sciences 03/2013; · 9.68 Impact Factor
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ABSTRACT: BACKGROUND: Radiofrequency ablation (RFA) of renal cell carcinoma (RCC) is used to obtain local control of small renal masses. However, available long-term oncologic outcomes for RFA of RCC are limited by small numbers, short follow-up, and lack of pathologic diagnoses. OBJECTIVE: To assess the oncologic effectiveness of RFA for the treatment of biopsy-proven RCC. DESIGN, SETTING, AND PARTICIPANTS: Exclusion criteria included prior RCC or metastatic RCC, familial syndromes, or T2 RCC. We retrospectively reviewed long-term oncologic outcomes for 185 patients with sporadic T1 RCC. Median follow-up was 6.43 yr (interquartile range [IQR]: 5.3-7.7). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The chi-square test and Wilcoxon rank-sum tests were used to compare proportions and medians, respectively. Disease-specific survival and overall survival (OS) were calculated using Kaplan-Meier analysis, then stratified by tumor stage, and comparisons were made using log-rank analysis. The 5-yr disease-free survival (DFS) and OS rates are reported. A p value <0.05 was considered statistically significant. RESULTS AND LIMITATIONS: Median tumor size was 3cm (IQR: 2.1-3.9cm). Tumor stage was T1a: 143 (77.3%) or T1b: 42 (22.7%). Twenty-four patients (13%) were retreated for residual disease. There were 12 local recurrences (6.5%), 6 recurrences in T1a disease (4.2%) and 6 in T1b disease (14.3%) (p=0.0196). Median time to recurrence was 2.5 yr. Local salvage RFA was performed in six patients, of whom five remain disease free at 3.8-yr median follow-up. Tumor stage was the only significant predictor of DFS on multivariate analysis. At last follow-up, 164 patients (88.6%) were disease free (T1a: n=132 [92.3%]; T1b: n=32 [76.2%]; p=0.0038). OS was similar regardless of stage (p=0.06). Five patients developed metachronous renal tumors (2.7%). Four patients developed extrarenal metastases (2.2%), three of whom died of metastatic RCC (1.6%). CONCLUSIONS: In poor surgical candidates, RFA results in durable local control and low risk of recurrence in T1a RCC. Higher stage correlates with a decreased disease-free survival. Long-term surveillance is necessary following RFA. Patient selection based on tumor characteristics, comorbid disease, and life expectancy is of paramount importance.
European urology 09/2012; · 7.67 Impact Factor
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ABSTRACT: The 2005 International Society of Urological Pathology (ISUP) Consensus Conference modified the Gleason grading system for prostate cancer. In the modified criteria, ill-defined glands with poorly formed lumina and large cribriform glands with smooth borders, classically described as Gleason pattern 3 adenocarcinoma, were redefined as Gleason pattern 4. To evaluate the clinical outcome of patients upgraded by the ISUP criteria, the histologic slides of 1240 consecutive radical prostatectomy specimens at a single institution were reviewed, and each case of adenocarcinoma was graded on the basis of the original and modified Gleason criteria. A total of 806 patients with prostate cancer of classical Gleason score 3+3=6 or 3+4=7 and modified Gleason score 6 to 8 were analyzed with a median overall follow-up of 12.6 years. In the study population, 34% of patients with classical Gleason score 3+3=6 prostate cancer were upgraded to modified Gleason score 7 or 8 by the ISUP criteria. Compared to patients with modified Gleason score 3+3=6 and patients with classical Gleason score 3+4=7, the upgraded patients were at intermediate risk for biochemical progression (paired log-rank P≤0.003) and metastasis (paired log-rank P≤0.04) after radical prostatectomy. The hazard ratio for upgrading was 1.60 (95% confidence interval, 1.09-2.35, P=0.02) for biochemical recurrence and 5.02 (95% confidence interval, 1.77-14.2, P=0.003) for metastasis. These results validate the prognostic value of the modified Gleason grading system and suggest that the recognition of an intermediate-risk histological pattern may be useful in the prognosis of patients with prostate cancer.
The American journal of surgical pathology 06/2012; 36(6):838-43. · 4.06 Impact Factor
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ABSTRACT: The term close surgical margin refers to a tumor extending to the inked margin of the specimen without reaching it. Current guidelines state that a close surgical margin should simply be reported as negative. However, this recommendation remains controversial and relies on limited evidence. We evaluated the impact of close surgical margins on the long-term risk of biochemical recurrence after radical prostatectomy.
We identified 1,195 consecutive patients who underwent radical prostatectomy and lymphadenectomy for localized prostate cancer at our institution from 1993 to 1999. In 894 of these patients associations between margin status and location, Gleason score, pathological stage, preoperative prostate specific antigen, prostate weight and age with the risk of biochemical recurrence were examined.
Of these 894 patients 644 (72%) had negative margins and of these patients 100 (15.5%) had close surgical margins. In the group with prostate specific antigen failure, median time to recurrence was 3.5 years. In the group without recurrence median followup was 9.9 years. Cumulative recurrence-free survival differed significantly among positive, negative and close surgical margins (p <0.001). On multivariate analysis a close surgical margin constituted a significant, independent predictor of recurrence (HR 2.1, 95% CI 1.04-4.33). Gleason score and positive margins were the strongest prognostic factors.
In this cohort close surgical margins were independently associated with a twofold risk of postoperative biochemical recurrence. Further evaluation of the clinical significance of close surgical margins is indicated as they might be an indicator of local recurrence and of relevance when considering salvage therapy.
The Journal of urology 05/2012; 188(1):91-7. · 4.02 Impact Factor
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New England Journal of Medicine 03/2012; 366(12):1143-50. · 53.30 Impact Factor
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ABSTRACT: OBJECTIVE: To evaluate the use of transperineal template-guided prostate biopsy for patients with persistently elevated PSA despite multiple negative prior biopsies. MATERIALS AND METHODS: A retrospective review was performed of patients with at least two prior prostate biopsies who underwent transperineal template-guided biopsy. Electronic medical records were reviewed to obtain relevant clinical, laboratory, and pathologic data. RESULTS: A total of 34 patients underwent transperineal template-guided biopsy. Patients had a mean of 3.7 ± 1.6 (range 2-8) prior biopsies, including prior negative transurethral resection (TUR) biopsy in 6 (17.6%) patients. Prostate cancer was detected in 17 (50%) of the 34 patients. Of these, 14 (82.4%) patients had cancer in the anterior prostate, 9 (52.9%) patients had cancer in the apical prostate, and 16 (94.1%) patients had cancer in either the anterior or apical prostate. Gleason score was 3+3 in 9 (52.9%) patients and 3+4 or greater in 7 (47.1%) patients. The mean number of positive cores was 4.5 ± 3.0 (range 1-11). Of the 17 patients with a diagnosis of cancer, 7 underwent radical prostatectomy, 7 underwent radiation therapy, 1 elected active surveillance, and 1 was deciding between surgery and radiation therapy; 1 patient received palliative chemotherapy for synchronous metastatic pancreatic carcinoma. Patients in whom cancer was detected had significantly smaller prostate volume, higher PSA, higher PSA density, and greater PSA velocity. CONCLUSIONS: Transperineal template-guided prostate biopsy is an effective technique for detecting cancer in patients with persistently elevated PSA despite multiple negative biopsies. It improves sampling of the anterior and apical prostate, and should be included as part of the diagnostic algorithm to reduce extensive repeat biopsy.
Urologic Oncology 02/2012; · 3.22 Impact Factor
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ABSTRACT: OBJECTIVES: Gleason score is important for prostate cancer (CaP) risk stratification and prognostication but has a significant rate of upgrading. We examined the effect of prostate size and age on upgrading of Gleason 6 CaP. MATERIALS AND METHODS: A retrospective review was performed of patients with Gleason 6 CaP who underwent radical prostatectomy from 2001 through 2010. Preoperative clinical and pathologic variables were assessed to determine association with risk of upgrading at prostatectomy. RESULTS: A total of 1,836 patients were identified with Gleason 6 on prostate biopsy. Upgrading was observed in 543 (29.6%) patients with a final Gleason score of 3+4 in 463 (25.2%), 4+3 in 49 (2.7%), and 8-10 in 31 (1.7%). On univariate logistic regression, age, prostate weight, and PSA were significant predictors of Gleason score upgrading and remained significant on multiple logistic regression. Prostate weight was inversely related to risk of upgrading. To further explore this effect, we performed multiple logistic regression to examine risk of Gleason 6, 7, or 8-10 disease in 2,493 patients with Gleason 6-10 at prostatectomy. After controlling for age and PSA, there was a progressively increased risk of Gleason 6, 7, and 8-10 disease with decreasing prostate weight. CONCLUSIONS: Older age, higher PSA, and smaller prostate gland size are associated with increased risk of Gleason score upgrading. The inverse relationship of prostate weight to risk of Gleason upgrading may be related to increased high-grade disease in smaller glands.
Urologic Oncology 12/2011; · 3.22 Impact Factor
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ABSTRACT: Radical cystectomy has been the standard treatment for muscle invasive bladder cancer. Combined modality therapy involving transurethral bladder tumor resection, external beam radiation and chemotherapy is an effective alternative to cystectomy in selected patients. Salvage cystectomy is reserved for those in whom combined modality therapy fails. We characterized complications associated with salvage cystectomy.
From 1986 to 2007 of 348 patients undergoing bladder sparing therapy 102 (29%) underwent salvage cystectomy, 91 of whom were treated at Massachusetts General Hospital after receiving combined modality therapy for T2-T4aNxM0 bladder cancer. Patients underwent transurethral bladder tumor resection followed by chemoradiation (40 Gy). Early assessment was performed by cystoscopy/re-biopsy. Patients with complete response continued with consolidation chemoradiation (total dose 64 Gy). Immediate salvage cystectomy (50 of 91) was performed for persistent disease, while delayed salvage cystectomy (41 of 91) was performed for an invasive recurrence. Complications were classified using the Clavien system.
Median patient age was 69.4 years (range 27.5 to 88.9) and median living patient followup was 12 years (range 0 to 23). Of the patients 99% (90 of 91) underwent ileal diversion. Complications of any grade within 90 days occurred in 69% (63 of 91) of patients and 16% (15 of 91) experienced major complications within 90 days. Of the patients 21% (19 of 91) required hospital readmission within 90 days. The 90-day mortality rate was 2.2% (2 of 91). Significant cardiovascular/hematological complications (pulmonary embolism, myocardial infarction, deep vein thrombosis, transfusion) within 90 days were more common in the immediate than in the delayed cystectomy group (37% vs 15%, p = 0.02). Tissue healing complications (fascial dehiscence, wound infection, ureteral stricture, anastomotic stricture, stoma/loop revisions) were more common in the delayed than in the immediate cystectomy group (35% vs 12%, p = 0.05).
Salvage cystectomy is associated with acceptable morbidity, although complication rates are slightly higher than for other cystectomy series. Immediate cystectomies have more cardiovascular/hematological complications while delayed cystectomies have more tissue healing complications.
The Journal of urology 12/2011; 187(2):463-8. · 4.02 Impact Factor
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ABSTRACT: We present our experience with penile sparing surgery for localized carcinoma in situ and T1 penile squamous cell carcinoma. We report outcomes and recommendations for a penile sparing approach.
A total of 60 patients underwent penile sparing surgery for penile squamous cell carcinoma since 1995. Four patients without recurrence had less than 6 months of followup and were excluded from study. Data included disease stage, cellular differentiation, tumor site, penile sparing surgery type and recurrence information.
Followup was adequate in 28 patients with carcinoma in situ and in 28 with T1 disease. The overall recurrence rate was 21.4% with equal recurrences of carcinoma in situ and T1 tumors (each 21.4%). Mean ± SD time to recurrence was 4.28 ± 2.81 years (range 0.5 to 11). More than 25% of recurrences developed after 5 years. Mean followup in censored patients was 5.47 ± 3.88 years (maximum 16). There was no difference in time to recurrence after carcinoma in situ and T1 tumors (p = 0.738). T1 tumors on the glans carried a slightly higher risk of recurrence (p = 0.049). At 5 years 13.8% of patients at risk had late recurrence with a mean time to recurrence of 7.25 ± 2.62 years. No patients with carcinoma in situ showed invasion or metastasis. Two patients with T1 disease presented with metastasis and 3 had late metastasis.
Penile sparing surgery is a safe option for local control for appropriate carcinoma in situ and T1 squamous cell carcinoma of the penis. Carcinoma in situ recurrence may be re-treated with penile sparing surgery. T1 tumors that recur require more aggressive resection. Our data show significant late recurrences in patients and the need for long-term followup.
The Journal of urology 08/2011; 186(4):1303-7. · 4.02 Impact Factor
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ABSTRACT: To define the role of positive surgical margins (PSMs) after radical retropubic prostatectomy as a predictor of biochemical failure (BCF) in prostate cancer with respect to pathologic stage.
A retrospective cohort study of 300 patients who had undergone radical retropubic prostatectomy from 1993 to 1995 was performed. The role of margin status and the length of the PSM in the progression to BCF was defined after controlling for the preoperative prostate-specific antigen level, Gleason score, tumor stage, tumor volume, seminal vesical invasion, lymphovascular invasion, and perineural invasion using a multivariate regression model. The median follow-up time was 12 years.
The presence of PSMs correlated with a shorter time to BCF in men with Stage pT2 disease (P<.0001) but not in men with Stage pT3 disease (P=.66). Of the patients with Stage pT2 disease and PSMs, the PSM length did not correlate with progression to BCF. PSMs predicted a shorter time to progression to BCF in patients with high- and low-volume pT2 disease (P=.0261 and P=.0003, respectively). Only PSMs predicted a shorter time to BCF on multivariate analysis in patients with Stage pT2 cancer (hazard ratio 2.33, 95% confidence interval 1.495-3.723). In patients with Stage pT3 disease, PSMs were not associated with an increased risk of BCF (hazard ratio 0.747, 95% confidence interval 0.328-1.703).
Surgical margin status did not affect the risk of BCF in patients with Stage pT3a disease; however, it did affect patients with Stage pT2 disease, irrespective of PSM length or disease volume. During 12 years of follow-up, the patients with PSMs and Stage pT2 disease had a risk of BCF similar to that of the patients with Stage pT3 disease.
Urology 03/2011; 78(1):121-5. · 2.43 Impact Factor
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ABSTRACT: Over the past 30 years, continuous progress in the application of nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance spectroscopic imaging (MRSI) to the detection, diagnosis and characterization of human prostate cancer has turned what began as scientific curiosity into a useful clinical option. In vivo MRSI technology has been integrated into the daily care of prostate cancer patients, and innovations in ex vivo methods have helped to establish NMR-based prostate cancer metabolomics. Metabolomic and multimodality imaging could be the future of the prostate cancer clinic--particularly given the rationale that more accurate interrogation of a disease as complex as human prostate cancer is most likely to be achieved through paradigms involving multiple, instead of single and isolated, parameters. The research and clinical results achieved through in vivo MRSI and ex vivo NMR investigations during the first 11 years of the 21st century illustrate areas where these technologies can be best translated into clinical practice.
Nature Reviews Urology 01/2011; 8(6):301-11. · 4.41 Impact Factor
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ABSTRACT: Statistical data from prostate cancer (PCa) clinics indicates that a large patient population discovered by annual prostate specific antigen (PSA) screening may have a latent form of the disease. However, current medical tests cannot differentiate slow from fast growing PCa, resulting in many unnecessary radical treatments and morbidities. It is thus necessary to find new screening tests that enable us to differentiate between fast- and slow-growing tumors. Inspired by the reported functions of spermine in carcinogenesis, we analyzed spermine and mRNA expression levels of rate-limiting enzymes in the spermine metabolic pathway for nine cases of PCa with accurately defined PSA velocity (Vpsa). Using MR spectroscopy, histopathology, laser-capture microdissection and real-time PCR techniques, we analyzed relationships between changes in spermine levels, mRNA expression levels of spermine anabolic and catabolic enzymes and human prostate cancer growth rates represented by serum Vpsa. The expression levels of spermine anabolic enzymes: ornithine decarboxylase (ODC1) and S-adenosylmethionine decarboxylase (AMD1) in benign epithelia surrounding cancer glands was logarithmically reduced with the increase of Vpsa (ODC1, p < 0.016; AMD1, p < 0.048), and antizyme (OAZ1) expression in cancer cells was increased with the increase of Vpsa (p < 0.001). Finally, we observed an inverse correlation between ODC1 and OAZ1 (p < 0.019) measured in cancer cells. These correlations may function to evaluate the aggressiveness of human prostate cancer, and assist patients and clinicians to select appropriate treatment strategies based on biological activities of individual tumors.
Cancer biology & therapy 05/2010; 9(9):736-42. · 2.64 Impact Factor
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W Scott McDougal
The Journal of urology 03/2010; 183(3):902; discussion 902. · 4.02 Impact Factor
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ABSTRACT: As current radiological approaches cannot accurately localize prostate cancer in vivo, biopsies are conducted at random within prostates for patients at risk for prostate cancer, leading to high false-negative rates. Metabolomic imaging can map cancer-specific biomolecular profile values onto anatomical structures to direct biopsy. In this preliminary study, we evaluated five whole prostates removed during prostatectomy from biopsy-proven cancer patients on a 7-tesla human whole-body magnetic resonance scanner. Localized, multi-cross-sectional, multivoxel magnetic resonance spectra were used to construct a malignancy index based on prostate cancer metabolomic profiles obtained from previous intact tissue analyses with a 14-tesla spectrometer. This calculated malignancy index is linearly correlated with lesion size and demonstrates a 93 to 97% overall accuracy for detecting the presence of prostate cancer lesions, suggesting the potential clinical utility of this approach.
Science translational medicine 01/2010; 2(16):16ra8. · 7.80 Impact Factor
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ABSTRACT: In clinical care of prostate cancer patients, an improved method to assess the risk of recurrence after surgical treatment is urgently needed. We aim to retrospectively evaluate the ability of ex vivo tissue magnetic-resonance-spectroscopy-based metabolomic profiles to estimate the risk of recurrence.
PCa recurrence is defined biochemically as the detection of serum PSA after radical prostatectomy. Sixteen consecutive PCa-recurrent cases, those with an initial PSA increase of 0.69 +/- 0.26 ng/ml monitored 47.7 +/- 2.6 months after prostatectomy were paired by age and Gleason score with cases without recurrence of the same pathological and clinical stages (n = 16/each). We analyzed ex vivo intact-tissue spectroscopy results from these 48 individuals at the time of prostatectomy at 14T. From these spectra, we identified the 27 most common and intense spectral metabolic regions for statistical analyses.
Principal component analysis (PCA) on these spectral regions from cases of clinical-stage-matched groups with and without recurrence identified four pathology-related principal components. Canonical analysis of these four and the first nine principal components for cases in the two groups defined metabolomic profiles as the canonical score that can differentiate the two groups with statistical significance. By applying the coefficients from PCA and canonical analysis to the pathological-stage-matched groups, recurrence was predicted with an accuracy of 78%.
Results indicate the potential of tissue metabolomic profiles measured with ex vivo spectroscopy to identify PCa aggressiveness in terms of cancer recurrence. With further study, this may greatly contribute to the future design of clinical strategy for personalized treatment of PCa patients.
The Prostate 12/2009; 70(7):710-7. · 3.48 Impact Factor
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New England Journal of Medicine 09/2009; 361(13):1292-9. · 53.30 Impact Factor
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ABSTRACT: We assessed and compared outcomes following open and laparoscopic radical prostatectomy.
Patients who were scheduled to undergo open or laparoscopic radical prostatectomy were enrolled in the study and followed prospectively. Before surgery the patients were administered a multi-item validated questionnaire, and were followed by telephone and with mail questionnaires periodically for 12 months. Complications were recorded from chart review and compared. Symptom distress and return to baseline for various parameters were compared between the 2 groups.
Of the patients 102 who underwent open prostatectomy and 104 treated with laparoscopic prostatectomy were enrolled in the study. At 1 year 90% in the open and 91% in the laparoscopic group returned the questionnaire. Symptom distress between the 2 groups did not differ at any time during followup. There was no significant difference in return to baseline at 1 year for continence, erectile function or physical function. Of the patients 95% had a return to baseline physical function, approximately 90% do not wear a pad and approximately 50% returned to baseline erectile function with or without phosphodiesterase type 5 inhibitors at 1 year. Although complications were few there was a significant difference in the number for laparoscopic vs open prostatectomy with a slightly higher rate of hematuria and lymphocele formation in the laparoscopic group. Cancer control at 1 year was excellent in both groups.
Radical prostatectomy is an effective form of therapy for patients with clinically localized cancer of the prostate. The open and laparoscopic techniques have similar functional outcomes, and these data provide patients a realistic view of what to expect following these 2 methods of radical prostatectomy.
The Journal of urology 08/2009; 182(3):956-65. · 4.02 Impact Factor
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ABSTRACT: Using proteomic techniques, we sought to identify novel protein biomarkers in tissue and urine from patients with transitional cell carcinoma (TCC).
Urinary and tissue proteomes were analyzed and differentially expressed proteins were identified by mass spectrometry. One of the proteins, cystatin B, was further analyzed in TCC tissue by immunohistochemistry and in urine by semiquantitative Western blot analysis.
Cystatin B tissue staining intensity significantly increased concordantly with TCC grade (P = 0.0008). Elevated urinary cystatin B levels correlated with increasing tumor grade (P = 0.062) and stage (P = 0.0047). Patients with elevated levels of cystatin B had a shorter mean +/- SE time to disease recurrence (12 +/- 1.82 months) compared with patients who had low levels (28.8 +/- 2.26 months; P = 0.0047). Similarly, patients with elevated cystatin B levels had a shorter time to grade/stage progression compared with patients with low urinary cystatin B (P = 0.0007). By multivariate Cox regression analysis, an elevated cystatin B level was the most significant variable predicting disease recurrence (hazard ratio, 3.8; 95% confidence interval, 1.5-9.5; P = 0.0049) and grade/stage progression (hazard ratio, 10.4; 95% confidence interval, 1.6-201.5; P = 0.0104).
Cystatin B is elevated in tissue and urine of bladder cancer patients. Cystatin B urine levels are positively correlated with tumor grade, stage, and shorter time to disease recurrence and progression. Consequently, cystatin B may be useful as a novel predictive biomarker in TCC of the bladder.
Clinical Cancer Research 03/2009; 15(3):1024-31. · 7.74 Impact Factor
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W Scott McDougal
The Journal of urology 11/2008; · 4.02 Impact Factor
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ABSTRACT: Tat-interacting protein 30 (TIP30), a transcriptional repressor for ERalpha-mediated transcription, possesses several characteristics of a tumor suppressor in certain human and mouse cells. It is reported that deletion of TIP30 gene preferentially increases tumorigenesis in the female knockout mice. Here, we analyzed TIP30 gene expression in the databases of several DNA microarray studies of human prostate cancer and show that TIP30 is specifically overexpressed in metastatic prostate cancers. We demonstrate that TIP30 nuclear expression is associated with prostate cancer progression and metastasis by immunohistochemical analysis in primary and metastatic prostate cancers. Consistent with these data, we also show that knockdown of TIP30 expression, through use of a short hairpin RNA-expressing plasmid, suppresses the cellular growth of PC3 and LNCaP prostate cancer cells. Ectopic overexpression of TIP30 stimulates metastatic potential of prostate cancer cells in an in vitro invasion assay, whereas knockdown of TIP30 inhibits the prostate cancer cells invasion. Finally, we demonstrate that ectopic overexpression of TIP30 enhances androgen receptor mediated transcription, whereas knockdown of TIP30 results in a decreased transcription activity. These data provide evidence that TIP30 plays a role in prostate cancer progression and that TIP30 overexpression may promote prostate cancer cell growth and metastasis.
International Journal of Cancer 09/2008; 123(4):810-6. · 5.44 Impact Factor
