Difficulties in interpreting specimens after neoadjuvant hormonal therapy and radiation with illustration of neuroendocrine differentiation

Pattern and cellular changes attributable to neoadjuvant hormonal therapy (NHT) might cause the unwary pathologist to overgrade or fail to recognize a treated prostatic cancer. Overdiagnosis and overgrading of surgical resections and biopsies can be avoided if an appropriate history of therapy is conveyed with the surgical specimen and if the pathologist is aware of the altered morphology of prostatic cancer treated by NHT alone or NHT plus radiation. Study of three prostatectomy specimens with post-NHT predominance of neuroendocrine cells showed positive staining for prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), as well as staining for chromogranin and synaptophysin in Paneth-like and small neuroendocrine cells. Difficult-to-interpret needle biopsies and transurethral resection (TUR) biopsies of prostate, where the urologic pathologist's suspicion of a radiation effect was confirmed by additional history, showed absence of the basal cell layer with 34 beta E12 keratin immunostaining in prostatic cancer glands, while basal cells were present in the nonneoplastic glands with radiation-induced atypia. Postradiation salvage prostatectomy specimens showed greater apoptosis after combined NHT and radiation than after radiation without NHT. Changes attributable to radiation and radiation plus NHT are illustrated.     

短期新辅助治疗对前列腺癌组织内聚集素蛋白表达的影响

目的　探讨短期新辅助治疗(NHT)后前列腺癌组织学及癌细胞内聚集素蛋白表达的变化及其临床意义。方法　采用免疫组织化学方法,对未行雄激素阻断治疗的 26例前列腺癌患者前列腺癌根治术(RP)标本(26份,无NHT组 ), 19例行 3个月NHT患者NHT前穿刺活检标本及NHT后的RP标本(NHT组),行前列腺癌组织内聚集素蛋白表达水平的测定,观察NHT对癌组织中聚集素蛋白表达水平的影响。结果　聚集素主要存在于前列腺癌细胞的细胞浆中,部分存在于细胞外间质。NHT组NHT前癌组织中聚集素表达较弱,染色强度平均值为 1 .42±0 .51,NHT后表达较强,染色强度平均值为 2 .16±0. 60(t=7. 10,P<0. 01);NHT组NHT后聚集素表达高于无NHT组 (染色强度平均值为 1 .57±0. 70,t=2 91,P<0 .01)。结论　雄激素阻断治疗可使前列腺癌细胞内聚集素适应性上调,针对聚集素的辅助治疗可提高激素阻断治疗的效果。     

Persistent expression of Aurora-A after neoadjuvant hormonal therapy as a predictor of a poor clinical outcome in patients undergoing radical prostatectomy for prostate cancer

OBJECTIVES: To characterize the changes in the expression of Aurora-A protein in prostate cancer before and after androgen-withdrawal therapy, and to assess the prognostic significance of the Aurora-A expression in patients undergoing radical prostatectomy (RP) after neoadjuvant hormonal therapy (NHT). PATIENTS AND METHODS: The study included 97 patients with clinically localized prostate cancer who received NHT followed by RP. Paired needle biopsy and corresponding RP specimens obtained from these patients were analysed for the expression of Aurora-A protein by immunohistochemical staining. These findings were then evaluated in relation to several clinicopathological factors. RESULTS: There were various levels of Aurora-A protein expression in most prostate cancer tissues before NHT; however, the Aurora-A expression in RP specimens after NHT was significantly down-regulated compared with that in corresponding needle-biopsy specimens. The expression level of Aurora-A in biopsy specimens was significantly associated with the biopsy Gleason score, but not with other factors available before RP. The Aurora-A expression in the RP specimens correlated significantly with the preoperative value of the serum prostate specific antigen and pathological stage, but not with any other clinicopathological factors examined. Furthermore, cell proliferative activity in the RP specimens, measured by Ki-67 immunostaining, was proportional to the expression of Aurora-A. The biochemical recurrence-free survival in patients with a persistent Aurora-A expression in RP specimens was significantly lower than that in those with a weak Aurora-A expression, but the expression level of Aurora-A was not an independent predictor of biochemical recurrence. CONCLUSIONS: Despite the lack of any independent significance, the expression level of Aurora-A in prostate cancer tissue after NHT, which might inversely reflect the therapeutic effect of NHT, could therefore be a useful variable for predicting biochemical recurrence in patients undergoing RP.     

前列腺癌根治术后无瘤生存期的影响因素分析

目的探讨前列腺癌根治术后无瘤生存期的影响因素及Bcl-2、C-erbB-2、Ki-67在前列腺癌中的表达及意义。方法回顾性分析51例前列腺癌患者根治术后无瘤生存期的影响因素，应用Cox比例风险模型进行多因素统计分析。对其中15例术前穿刺标本及手术切除标本行3种癌基因蛋白免疫组化检查，分析其表达与术后无瘤生存期的关系。结果Cox比例风险模型发现有意义的因素为年龄(P=0．011)、术前雄激素全阻断治疗(P=0．017)、阳性切缘(P=0.000)、切除标本Gleason评分(P=0．002)、术前或术后行睾丸切除(P=0．040)。前列腺癌穿刺标本、切除标本中Bcl-2、C-erbB-2、Ki-67蛋白表达与术后无瘤生存期存在相关性。结论标本阳性切缘是影响无瘤生存期的因素，前列腺癌根治术术前雄激素全阻断治疗可提高患者术后无瘤生存期，术中探查未发现肿大淋巴结时未行盆腔淋巴结清扫对术后无瘤生存时间无明显影响，术前或术后睾丸切除患者的无瘤生存期明显好于未行睾丸切除患者。Ki-67、Bcl-2与C—erbB—2可作为术前、术后预测前列腺癌患者根治术后无瘤生存期的指标。     

Molecular markers and their prognostic impact in patients with advanced prostate cancer undergoing intermittent androgen suppression

OBJECTIVE: Tumour features were evaluated during intermittent androgen suppression (IAS), and their prognostic impact on the first off-treatment time was analysed. PATIENTS AND METHODS: Twenty patients with advanced prostate cancer underwent three consecutive prostate biopsies during the first cycle, namely at the beginning of androgen deprivation, 8 months after continuous therapy and at the time of prostate-specific antigen (PSA) progression above 20 ng/ml. Biopsy specimens were immunohistochemically processed and analysed for the apoptotic index (AI), Ki-67, p53 and Bcl-2 to investigate eventual changes over time. Correlations and regression analysis were performed to assess the prognostic significance of clinical and pathological parameters in predicting the first off-treatment time. RESULTS: In contrast to the AI, p53 and Bcl-2, Ki-67 was the only marker that significantly changed over time (P=0.008). The first off-treatment time correlated significantly with pretreatment PSA (r=-0.594; P<0.01), testosterone recovery time (r=0.590; P=0.013) and biopsy grade (r=-0.738; P<0.01); only the latter gaining an independent factor in the multivariate analysis (P=0.022). CONCLUSIONS: During IAS, Ki-67 was the only molecular marker that consistently changed over time. However, it did not correlate with off-treatment time that was predicted independently by the initial biopsy grade only. First off-treatment time was best predicted by clinical parameters and molecular markers from needle biopsies did not further contribute to a better patient selection.     

Clusterin expression is significantly enhanced in prostate cancer cells following androgen withdrawal therapy

INTRODUCTION AND OBJECTIVES: Progression of prostate cancer to androgen independence (AI) results in part from the upregulation of anti-apoptotic genes following androgen withdrawal, and androgen-independent disease remains the primary obstacle to improved survival. Testosterone-repressed prostate message-2 (TRPM-2) encodes the anti-apoptotic protein clusterin, which is upregulated in response to cellular compromise as observed in normal and malignant tissues undergoing apoptosis. Systemic administration of antisense clusterin oligonucleotides in prostate cancer xenograft models delays progression to AI and enhances chemosensitivity. The objective of this study was to define changes in clusterin expression following neoadjuvant hormone therapy (NHT) in prostate cancer patients. MATERIALS AND METHODS: Archival radical prostatectomy (RP) specimens were obtained for 128 patients who received either no NHT or treatment for 2-8 weeks, 3 months, or 8 months. Paired needle biopsy specimens were acquired for 30 patients and all tissues were subjected to clusterin immunohistochemistry. Western blot analysis was performed on frozen tissue from 5 untreated and 5 treated patients. RESULTS: Clusterin expression in malignant prostatic tissue was significantly greater in patients who underwent preoperative NHT (P < 0.001). Needle biopsies obtained prior to NHT consistently demonstrated lower staining intensity than corresponding RP specimens (P < 0.001). Western blot analysis confirmed clusterin levels increased 17-fold beginning within 4 weeks after androgen withdrawal. CONCLUSIONS: Upregulation of clusterin levels following androgen ablation therapy may represent an adaptive cell survival response following apoptotic signals like androgen withdrawal. These findings support clusterin as a valid therapeutic target in strategies employing novel multimodality therapy for advanced prostate cancer.     

Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

Active surveillance provides a unique opportunity to study biomarkers of prostate cancer behaviour, although only small volumes of tumor tissue are typically available. We have evaluated a technique for constructing tissue microarrays (TMAs) from needle biopsies for assessing immunohistochemical markers in localized prostate cancer managed by active surveillance. TMAs were constructed from diagnostic prostate biopsies for 60 patients with localized prostatic adenocarcinoma in a prospective cohort study of active surveillance. Radical treatment was recommended for a prostate-specific antigen (PSA) velocity greater than 1 ng ml(-1) per year or adverse histology in repeat biopsies, defined as Gleason score > or =4+3 or >50% of cores involved. Sections from the TMAs were stained with H&E, P63/AMACR and Ki-67. Time to radical treatment was analysed with respect to clinical characteristics and Ki-67 LI. At a median follow up of 36 months, 25/60 (42%) patients had received radical treatment. On univariate analysis, PSA density (P=0.001), Gleason score (P=0.001), clinical T stage (P=0.01), Ki-67 LI (P=0.02) and initial PSA (P=0.04) were associated with time to radical treatment. On multivariate analysis, PSA density (P=0.01), Ki-67 LI (P=0.03) and Gleason score (P=0.04) were independent determinants of progression to radical treatment. TMAs constructed from prostate needle biopsies can be used to assess immunohistochemical markers in localized prostate cancer managed by active surveillance. Ki-67 LI merits further study as a possible biomarker of early prostate cancer behaviour.     

前列腺癌根治术前盆腔淋巴结微转移检测的研究

目的 明确新辅助治疗后前列腺癌根治术前,real-time PCR检测盆腔淋巴结微转移的意义.方法 2007年8月至2010年3月对21例临床局限性前列腺癌病例,根据病理检查阳性(A组)、real-time PCR检查前列腺特异性抗原(PSA)mRNA和前列腺特异性膜抗原(PSMA)mRNA阳性(B组)、病理检查及real-time PCR检查PSA mRNA及PSMA mRNA均阴性(C组)进行分组,D组为对照组.术前行淋巴管造影显示盆腔淋巴结,对可疑淋巴结在X线定位下穿刺抽吸淋巴液,用real-time PCR方法检测淋巴液中PSA mRNA和PSMA mRNA的表达,阳性表达提示淋巴结转移的存在,术后对淋巴结组织切片进行免疫组化检查.结果 对术前盆腔淋巴结穿刺抽吸淋巴液用real-time PCR方法检测PSA mRNA和PSMA mRNA的表达,证实有14例淋巴结存在微转移,术后对清扫淋巴结进行免疫组化检查有3例存在淋巴结转移,A组与B组PSA mRNA和PSMA mRNA的表达存在明显的差异;A、B组淋巴液中PSA mRNA及PSMA mRNA的表达明显高于淋巴结(P＜0.01).结论 采用real-time PCR方法检测淋巴液中PSA和PSMA mRNA的表达有利于探测到淋巴结微转移的存在,术前穿刺淋巴结抽吸淋巴液提高了术前前列腺癌分期的准确性.     

The value of EZH2, p27kip1, BMI‐1 and MIB‐1 on biopsy specimens with low‐risk prostate cancer in selecting men with significant prostate cancer at prostatectomy

OBJECTIVE

To assess the additional prognostic value of the molecular markers EZH2, MIB‐1, p27^kip1 and BMI‐1 on needle biopsies from men with low‐risk prostate cancer, as this disease in needle biopsies shows a heterogeneous clinical outcome, and while it is known that the expression of these tissue markers is predictive of the clinical outcome after radical prostatectomy (RP) their value in prostate biopsies is largely unknown.

PATIENTS AND METHODS

The study included men participating in a screening study, diagnosed with low‐risk prostate cancer and subsequently treated with RP. Immunohistochemical staining for EZH2, MIB‐1, p27^kip1 and BMI‐1 on the needle biopsies were (semi)quantitatively scored and expression levels were related to significant disease at RP. Clinical low‐risk prostate cancer was defined as a prostate‐specific antigen (PSA) level of ≤10 ng/mL, clinical T‐stage ≤2, biopsy Gleason score ≤6, a PSA density of <0.20 ng/mL/g and two or fewer positive cores. Significant PC at RP was defined as presence of any of extracapsular extension, Gleason pattern 4/5, or tumour volume ≥0.5 mL.

RESULTS

In all, 86 biopsy specimens were included; there was high EZH2 expression (>1.0%) in 42% and a low p27^kip expression (<90%) in 63%. Significant disease was present in 44 (51%) RP specimens. A high EZH2 (odds ratio 3.19, P = 0.043) and a low p27^kip1 (4.69, P = 0.036) were independent predictors for significant prostate cancer at RP.

CONCLUSIONS

The determination of EZH2 and p27^kip1 on diagnostic needle biopsies supports the selection of men with indolent prostate cancer at RP. Especially p27^kip1 could improve the pretreatment risk assessment of patients with low‐risk prostate cancer.     

Immunohistochemical expression of Ki-67 antigen, cox-2 and Bax/Bcl-2 in prostate cancer; prognostic value in biopsies and radical prostatectomy specimens

PURPOSES: To elucidate the prognostic value of the immunohistochemical (IHC) expression of Bcl-2, Bax, Cox-2 and Ki-67 antigen in biopsy cores (C) and surgical specimens (SP) of prostate cancer (PC) and to determine the C to SP reproducibility. MATERIAL AND METHODS: The IHC study was carried out in 91 patients operated by means of radical prostatectomy (RP) with available formalin-fixed paraffin-embedded material from both C and SP. RESULTS: The IHC expression of Bcl-2 in C and SP was very low (5%). Bax was expressed in almost all the patients and did not show any prognostic value. We observed a good reproducibility between C and SP for all molecules except with Bax. In prostate C, Ki-67 and Cox-2 were considered positive in 42.9% and 67% of the patients respectively, and were related to disease-free survival in the univariate analysis. The expression of these two markers in SP was observed in 51.6% and 79.1% of the patients and the expression of Ki-67 in SP maintained its independence as prognostic factor in the multivariate analysis related to disease-free survival. CONCLUSIONS: The IHC expression of Ki-67 and Cox-2 proteins in our study do offer valuable prognostic information, mostly the first one. Thus, we think these markers might be studied in larger series of patients for its further validation as prognostic factors in prostate biopsies.     

Effects of Estrogens Only on the Prostates of Aging Men

Purpose

The effects of estrogen only on prostate tissue were studied in 9 aging male transexuals who had undergone orchiectomy.

Materials and Methods

Prostate volume was measured by ultrasound. Biopsies were stained for prostatic acid phosphatase (PAP), prostate specific antigen (PSA), Ki-67 and sex steroid receptors.

Results

Prostates were small, and biopsies showed PAP and PSA in most cases. No malignancy was found. Few androgen receptors were detectable but there were ample estrogen and progesterone receptors in stroma and epithelium.

Conclusions

Prostates were small after long-term estrogens only. The sex steroid receptor content was considerably changed. PSA and PAP in the specimens suggested that their production does not depend on testicular androgens alone.     

A comparison of the biological features between prostate cancers arising in the transition and peripheral zones

OBJECTIVES: To investigate differences in the biological features of prostate cancer according to the zonal origin. PATIENTS AND METHODS: Among 172 consecutive patients who had a radical prostatectomy (RP), the study included 124 diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer, defined according to whether there was > 70% of the cancer area in the TZ or PZ, respectively. The clinicopathological features were then compared between these groups. In addition, the RP specimens were stained immunohistochemically with antibodies to Ki-67, Bcl-2, matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF). RESULTS: Twenty-four patients were diagnosed as having TZ cancer and the remaining 100 as having PZ cancer. Prostate specific antigen (PSA) values in patients with TZ cancer were significantly higher than in those with PZ cancer. Tumour volume in TZ cancer was significantly greater than that in PZ cancer, but there was no significant difference in biochemical recurrence-free survival between the groups. Immunohistochemistry showed that despite there being no differences in Bcl-2 and VEGF expression between TZ and PZ cancers, there was significantly greater expression of Ki-67, MMP-2 and MMP-9 in PZ than TZ cancers. CONCLUSIONS: Despite there being no significant difference in biochemical recurrence-free survival after RP between patients with TZ and PZ cancers, there was less cell proliferation and biomarker levels related to invasive potential in TZ than in PZ cancers.     

Comparison of Gleason scores from sextant prostate biopsies and radical prostatectomy specimens.

OBJECTIVES: We compared the Gleason scores obtained from sextant prostate biopsy and radical prostatectomy (RP) specimens in patients with localized prostate cancer. PATIENTS AND METHODS: Sixty-one patients having a clinical diagnosis of localized prostate cancer underwent needle biopsy under transrectal ultrasonography (TRUS) and RP. Grading and staging were assigned based on Gleason scores and the TNM system, respectively. RESULTS: Mean patient age was 65.5 +/- 13.43 years and mean PSA level was 14.69 +/- 3.95. Mean Gleason score for prostate biopsy and RP specimen were 5.85 +/- 0.7 and 6.34 +/- 1.44, respectively. With respect to clinical stage, there were 20 patients in stage 1 and 41 patients in stage 2 prostate cancer. Comparing the Gleason scores, the biopsy score was lower in 26 (42.26%) and higher than RP specimens in 7 (11.84%) cases, and there was agreement between the biopsy and RP specimens in 28 (45.9%) patients. The difference between the two Gleason scores was +/- 1 for 18 patients (29.5%) and +/- 2 or more for 17 patients (27.86%). CONCLUSION: In our study, high Gleason score biopsies with elevated PSA level (>10 ng/ml) were risk factors for extraprostatic extension, and we demonstrated that Gleason scores were significantly correlated with seminal vesicle and lymph node invasion (p < 0.05). The Gleason scores of biopsy and RP specimens agreed with 45.9% of TRUS-guided sextant prostate biopsies, and this ratio was 91.1% in moderately differentiated tumors Copyright 2001 S. Karger AG, Basel     

Application of the monoclonal antibody Ki-67 on prostate biopsies to assess the fraction of human prostatic carcinoma.

The feasibility of using the monoclonal antibody Ki-67 as a proliferation marker in human prostatic carcinoma was studied on aspiration and core biopsy specimens obtained from 50 patients suspected of having prostate cancer. In 32 prostatic adenocarcinomas the Ki-67 index varied from 0.3 to 13.3% (mean 4.3) in cytological smears and from 0.8 to 17.8% (mean 5.1) in frozen sections from histological core biopsies. No significant correlation between the percentage of cells positive for Ki-67 and the histological tumor differentiation could be established. In 18 patients with benign prostatic hyperplasia the Ki-67 index varied from 0 to 3.0% (mean 1.2) and from 0 to 3.8% (mean 1.4) in cytological and histological material, respectively. The differences in the observed Ki-67 index between benign and malignant prostatic tissues are of statistical (p less than 0.001) and of clinical significance. Nine patients who underwent endocrine treatment or radiotherapy entered a followup protocol in which the Ki-67 staining procedure was applied to periodically obtained cytological aspiration biopsies. During month 1 after the start of therapy a statistically significant (p less than 0.05) decrease in the Ki-67 index to 58% of the initial values was found, while at 2 and 3 months the proliferative fraction showed a further decrease to 27 and 7%, respectively. As a marker, the monoclonal antibody Ki-67 was shown to provide a reliable method to estimate the proliferative cell fraction of human prostate cancer.     

Detection of the 67-kD laminin receptor in prostate cancer biopsies as a predictor of recurrence after radical prostatectomy.

OBJECTIVES: Reliable prognostic indicators are needed for a better pretherapeutic assessment of the agressiveness of organ-confined prostate cancer (PC) lesions. The 67-kD laminin receptor (67LR) is a cell-surface-associated protein involved in the acquisition of the invasive and metastatic phenotype of a variety of human cancer cell types. We have previously shown that 67LR detection in PC tissues from radical prostatectomy (RP) specimens is an independent predictor of biochemical (PSA) relapse in patients with clinically localized PC. In this study, we assessed 67LR detection in diagnostic PC biopsies as a predictor of biochemical relapse after RP. METHODS: Diagnostic biopsy and subsequent RP tissue specimens from 151 patients with clinically localized PC were immunohistochemically analyzed for 67LR expression. The level of 67LR expression was evaluated by both intensity and extent of the staining. Clinicopathological preoperative and postoperative parameters, including 67LR expression, were correlated with each other and tested as predictors of biochemical relapse. RESULTS: 67LR was detected in 67.5 and 68.2% of biopsies and RPs, respectively. 67LR detection in RP specimens was an independent predictor of relapse. The level of 67LR expression in the biopsy was significantly associated with the biopsy Gleason score (p<0.05) but failed to predict the pathological stage (p>0.1). Biochemical progression-free estimates for patients whose biopsy did or did not express the protein differed with only borderline statistical significance (p = 0.05). Multivariate analysis identified biopsy Gleason score as the only independent preoperative predictor of recurrence. Significant discrepancies in levels of 67LR expression were found between matched biopsy and RP specimens (p<0.05), with exact agreement rates <40%. CONCLUSIONS: 67LR detection in PC biopsies was not a significant preoperative predictor of outcome after RP. Heterogeneity of 67LR expression and biopsy sampling errors most likely represented the main reasons for discordant results between biopsy and RP specimens.     

Expression of potential molecular markers in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy

The objective of this study was to evaluate the expression levels of multiple potential molecular markers in prostate cancer to clarify the significance of these markers as prognostic indicators in patients undergoing radical prostatectomy (RP). This study included a total of 193 patients with clinically organ-confined prostate cancer who underwent RP without any neoadjuvant therapies. Expression levels of 12 proteins, including Ki-67, p53, androgen receptor (AR), matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor, Aurora-A, Bcl-2, clusterin, heat shock protein 27 (HSP27), HSP70, and HSP90, in RP specimens obtained from these 193 patients were measured by immunohistochemical staining. Of the 12 molecules, Ki-67, p53, AR, MMP-2, MMP-9, and HSP27 expression were significantly associated with several conventional prognostic factors. Univariate analysis identified these 6 markers as significant predictors for biochemical recurrence as well, while prostate-specific antigen, Gleason score, seminal vesicle invasion (SVI), surgical margin status (SMS), lymph node metastasis, and tumor volume were also significant. Of these significant factors, Ki-67 expression, SVI, and SMS appeared to be independently related to biochemical recurrence by multivariate analysis. Furthermore, there were significant differences in biochemical recurrence-free survival according to positive numbers of these three independent risk factors. These findings suggest that consideration of expression levels of potential molecular markers in RP specimens, in addition to conventional prognostic parameters, would contribute to accurate prediction of biochemical recurrence following RP in patients with clinically localized prostate cancer, and that combined evaluation of Ki-67 expression, SVI, and SMS would be particularly useful for further refinement of the system in predicting biochemical outcome.     

Absence of Bcl-2 expression favors response to the short-term administration of diethylstilbestrol diphosphate in prostate Cancer

BACKGROUND: Neoadjuvant hormone therapy remains a controversial issue in spite of multiple studies having been performed. METHODS: We performed short-term (10 days) treatment with diethylstilbestrol (DES) in 30 patients with stages T2 or T3 prostate cancer (PCa). All the patients underwent needle core prostate biopsy before and radical prostatectomy within a month after the start of the endocrine therapy. The histological effects in PCa and the changes in morphological and clinical parameters and their association were elucidated. RESULTS: Serum PSA (P < 0.001), Ki-67 PI (P = 0.022), and AR (P = 0.002) expression decreased after the treatment. An obvious effect (Grade 1-3) of endocrine treatment was seen in 11 of 30 patients and was associated with a prominent PSA decrease (P = 0.0274) and with older age (P = 0.0026). Pre-treatment specimens from a group without any effects of endocrine therapy had a higher frequency of Bcl-2 positivity (57.9%) compared to the group of Grade 1-3 effects (27.3%). Prostatectomy specimens presented with significantly higher AI in Bcl-2 negative cases (P = 0.0029) and pre treatment Bcl-2 was associated with a higher AI in Grade 1-3 patients (P = 0.0393). CONCLUSIONS: Older age is a predictor of histological effects in short-term hormone treatment of PCa. A lower Bcl-2 in biopsy specimens presented more frequently in the patients who experienced a prominent effect of endocrine therapy, and it was also useful to predict a significantly higher AI in Grade 1-3 patients. Histological effects are also associated with the PSA decrease, reflecting the clinically meaningful shrinkage of tumors and a decrease of tumor burden.     

p53 and bcl-2 immunohistochemistry in pretreatment prostate needle biopsies to predict recurrence of prostate cancer after radical prostatectomy

PURPOSE: Immunohistochemical staining of radical prostatectomy specimens for p53 and bcl-2 proteins has been shown to correlate with prostate specific antigen (PSA) recurrence in a series of patients at our institution. We analyzed the relationship between staining of diagnostic prostate needle biopsies for p53 and bcl-2, and PSA recurrence. MATERIALS AND METHODS: From 1986 to 1993, 335 radical prostatectomies were performed at our hospital. Of the prostatectomy specimens 199 had been evaluated for p53 and bcl-2 proteins in a prior series. Of 139 patients with biopsy material available for analysis 129 had enough for evaluation of 1 or both markers. Prospectively obtained clinical followup data were available, with a mean followup of 6 years. Commercially available antibodies were used for immunohistochemical staining. RESULTS: The overall PSA recurrence rate was 37.6% for 199 radical prostatectomy cases and 37.9% for 129 with biopsy immunohistochemical staining. Staining of prostatectomies correlated well with PSA recurrence for p53 (p = 0.004) and bcl-2 (p = 0.001). However, biopsy staining did not correlate with prostatectomy staining or PSA recurrence for either marker. CONCLUSIONS: The p53 and bcl-2 biomarkers appear to be important to predict recurrence of prostate cancer when prostatectomy specimens are analyzed but this usefulness is not apparent with immunohistochemical staining of prostate biopsies. This difference may reflect sampling error and/or the heterogeneous nature of prostate cancers, and deserves further study.