The expression of vascular endothelial growth factor is associated with the risk of cancer progression after radical prostatectomy

OBJECTIVE: To analyse the prognostic value of vascular endothelial growth factor (VEGF) in men with clinically localized prostate cancer. PATIENTS AND METHODS: Paraffin wax-embedded sections from the radical prostatectomy (RP) specimens of 40 men operated for clinically localized prostate cancer were used to build tissue microarrays. Of these patients, 17 had cancer progression and bone metastases after RP (group 1), and 23 remained free-of-tumour recurrence after RP (group 2). VEGF-A expression was examined in the RP specimens using immunohistochemistry. RESULTS: The groups had similar tumour characteristics in terms of prostate-specific antigen level, Gleason score, and pathological stage. VEGF-A expression was significantly higher in group 1 than in group 2 (P=0.046). In logistic regression analysis, VEGF-A expression was the most significant predictive factor of cancer progression after RP. CONCLUSION: VEGF-A expression in prostate cancer tissue is associated with the risk of cancer progression after RP. These results suggest that VEGF-A expression has a prognostic impact in clinically localized prostate cancer.     

前列腺癌组织中蛋白表达与内分泌治疗后进展的相关性研究

目的 探讨前列腺癌内分泌治疗前癌组织中多种蛋白标记表达与内分泌治疗后发生进展的相关性,筛选内分泌治疗后进展的预测因子.方法 收集116例接受内分泌治疗的前列腺癌患者的临床病理资料,检测患者内分泌治疗前癌组织中雄激素受体(AR)、上皮型钙黏附索(E-cad-herin)、嗜铬粒蛋白A(CgA)、核增殖抗原(Ki67)、凋亡抑制蛋白(Survivin)、EZH2、hepsin蛋白表达,应用Cox比例风险模型进行多因素分析.结果 Ki67、EZH2、Survivin 3种蛋白表达与传统临床病理学因素存在Spearman等级相关.单因素分析中发现临床分期(P<0.001)、Gleason评分(P=0.005)、治疗前血清PSA值(P<0.001)以及Ki67(P=0.032)、Survivin蛋白(P=0.002)表达与内分泌治疗后的进展相关,多因素分析结果 显示临床分期(T_x N_+/M_+)(P<0.001)、高病理分级(Gleason评分≥8分)(P-0.038)和Survivin蛋白高表达(p＝0.031)是内分泌治疗后进展的重要危险因素.其中T_x N_+/M_+者67例(57.8%),Gleason评分≥8分者56例(48.3%),Survivin蛋白高表达者91例(78.4%). 结论 临床分期、病理分级、Survivin蛋白表达对于预测前列腺癌内分泌治疗后进展有重要意义.     

Relationship of p21(WAF1) expression with disease-free survival and biochemical recurrence in prostate adenocarcinomas (PCa).

BACKGROUND: The p21(WAF1) gene is considered to be one of the major regulators of the cell cycle. Its level of expression has been shown to correlate with pathologic stage and Gleason score in prostatic cancer. However, its relationship to clinical outcome is not yet well-characterized. METHODS: Immunohistochemical staining for p21(WAF1) protein expression was performed in 62 consecutive radical prostatectomy specimens from our institution. The results were correlated with the disease-free survival and biochemical recurrence of the patients. RESULTS: Thirty-four of the 62 patients were Caucasian and 28 were African American. There was a significant correlation between p21(WAF1) expression and biochemical recurrence after radical prostatectomy (P < 0.0095). However, while p21(WAF1) staining in prostate cancer was a prognostic indicator of disease-free survival in Caucasians (P < 0.0001), it appeared not to be a factor in African-American men (P = 0.908). CONCLUSIONS: This study suggests that p21(WAF1) may have a role in the pathogenesis and progression of prostate carcinoma, and may serve as a predictor of biochemical recurrence of this tumor. The differences in the values of p21(WAF1) as a prognostic marker of disease-free survival in Caucasians vs. African Americans suggest that progression of prostate cancer may have different mechanisms in different ethnic groups.     

Prognostic significance of Ki-67 expression in advanced prostate cancers in relation to disease progression after androgen ablation

OBJECTIVE: This study was performed to examine the expressions of Ki-67 antigen, bcl-2 and p53 oncoprotein and to assess their capacity to predict the short-term response to the initial endocrine treatment and disease progression in prostate cancer. METHODS: Formalin-fixed and paraffin-embedded tumor tissues from a total of 73 patients with untreated prostate cancers were collected by transrectal ultrasound-guided biopsy. All patients with stage C or D prostate cancers had received continuous endocrine treatment. Ki-67 antigen, p53 and bcl-2 oncoprotein were detected by immunohistochemical methods. RESULTS: Short-term response to initial endocrine therapy judged at 3 months showed a significant correlation with Ki-67 labeling index (LI) and bcl-2 expression. Multivariate analysis showed that only a high Ki-67 LI was an independent potential predictor of prostate-specific antigen failure or the appearance of new metastasis. CONCLUSIONS: The findings suggested that the Ki-67 LI was the most useful parameter to predict disease progression after the initial endocrine treatment. Additional studies must be performed to evaluate the prognostic significance of both cell proliferation and apoptosis in detail.     

Clinical survey of prostate cancer

OBJECTIVES: Treatment trends and outcomes for prostate cancer in our hospital were reported. MATERIAL AND METHODS: A total of 482 patients with prostate cancer treated in our hospital between January, 1990 and December, 2004. RESULTS: The age distribution was from 51 to 99 years-old, with the mean age of 72.9 years-old at onset. The number of prostate cancer patients, especially asymptomatic patients with PSA elevation, have increased recently. As for the clinical stage, 92 cases (19.1%), 238 cases (49.4%), 48 cases (10.0%) and 104 cases (21.6%) were stage A, B, C and D, respectively. 425 cases (88.2%) received some form of endocrine therapy. Retropubic prostatectomy or external beam radiation therapy was performed in 77 and 57 cases, respectively all cases. The cause-specific 5-year survival rate of the 482 cases was 79.7%, comprising 100% for stage A1, 96.8% for stage A2, 89.4% for stage B, 79.9% for stage C and 42.9% for stage D. The cause-specific 5-year survival was significantly better in the latter patients (1997-2004) than the former patients (1990-1996) in stage C (p = 0.0226), D (p = 0.0448). In stage C patients, the retropubic prostatectomy (with endocrine therapy) group, increased in the latter period and showed longer cause-specific 5-year survival than the endocrine therapy group (p = 0.0027). In stage D2 patients, chemo-endocrine therapy with VP-16, ADM and CDDP refractory and cause-specific 5-year survival was longer than endocrine therapy alone (p = 0.0467, P = 0.0381). CONCLUSION: Our results suggest that retropubic prostatectomy with endocrine therapy and chemo-endocrine therapy are useful for stage C and D prostate cancer patients, respectively.     

前列腺癌中P53的表达及其临床意义

目的:探讨P53在前列腺癌中的表达及其临床意义。方法:应用免疫组化Elivision法,检测45例前列腺癌和10例前列腺增生组织标本P53的表达,分析P53表达与前列腺癌分期、分级、前列腺特异性抗原(PSA)水平、内分泌治疗效果及预后的关系。结果:P53在前列腺癌和前列腺增生中阳性表达率分别为51.1%和10.0%(P<0.05);D期和A~C期前列腺癌中阳性表达率分别为70.0%和25.0%(P<0.05);Gleason评分≤7分和>7分前列腺癌中阳性表达率分别为14.3%和56.7%(P<0.05);PSA≤10μg/L和>10μg/L前列腺癌中阳性表达率分别为20.0%和60.0%(P>0.05);在内分泌治疗有效和无效前列腺癌中阳性表达率分别为25.0%和72.3%(P<0.05);LogRank检验分析P53阴性表达前列腺癌患者的生存时间明显长于P53阳性表达前列腺癌患者(P<0.05)。结论:P53表达可以作为判定前列腺癌预后的分子标记,同时可以预测内分泌治疗的效果。     

Expression of interleukin-8 gene in radical prostatectomy specimens is associated with advanced pathologic stage

BACKGROUND: We previously reported that relative expression of E-cadherin, matrix metalloproteinases (MMPs)-2 and -9, and vascular endothelial growth factor (VEGF)/vascular permeability factor in radical prostatectomy specimens (RP) can distinguish organ-confined cancers from advanced prostate cancers. Here, we evaluate the expression of interleukin-8 (IL-8) and basic fibroblast growth factor (bFGF), two other genes involved in angiogenesis and metastasis, in RP specimens. METHODS: The expression level of IL-8 and bFGF mRNA in the invasive edge of 41 prostate cancers of different stages was determined using a rapid colorimetric in situ hybridization (ISH) technique. Gene expression levels of IL-8 and bFGF were correlated with the Gleason score and pathologic stage to ascertain their relationship to prostate cancer progression. RESULTS: The expression of IL-8 and bFGF genes was detected by ISH in histologically normal prostate gland epithelium as well as in glands with foci of cancer. Increased mRNA expression of IL-8 was associated with both the Gleason score and pathologic stage of tumors and distinguished organ-confined from non-confined tumors (P = 0.002). In contrast, the expression of bFGF mRNA did not correlate with the Gleason score or pathologic stage. CONCLUSIONS: Overexpression of Il-8 mRNA, but not bFGF mRNA, in RP specimens is directly associated with progression of prostate cancer.     

Expression of sialylated MUC1 in prostate cancer: Relationship to clinical stage and prognosis

Aim: MUC1 is distributed among a variety of normal epithelial tissues, and overexpression of MUC1 is detected in several human cancers. This study aimed to elucidate whether sialylated MUC1 expression correlated with: (i) clinical stage of prostate cancer; (ii) pathological grade of prostate cancer; (iii) pretreatment serum level of prostate‐specific antigen (PSA); or (iv) the disease prognosis in patients with prostate cancer who received endocrine therapy. Methods: We collected 57 biopsy specimens from prostate cancer patients treated with only endocrine therapy, and 10 specimens of normal prostates. These specimens were stained immunohistochemically by using a novel monoclonal antibody, MY.1E12, to detect sialylated MUC1. The levels of expression, clinical stages, pathological grades, pretreatment serum level of PSA and the prognoses of the patients were statistically analyzed for correlations. Results: There were statistically significant correlations between the expression of sialylated MUC1 and pathological grades (WHO grade, P < 0.01; Gleason score, P < 0.05). Expression increased according to the progression of the disease (existence of clinical metastasis, P < 0.05; clinical T‐stage, P < 0.01). Patients with high serum levels of PSA had higher expression than those with low levels (P < 0.01). The level of sialylated MUC1 significantly correlated with progression‐free survival (P < 0.01) and cause‐specific survival (P < 0.01) according to univariate analyses. Furthermore, the level significantly correlated with progression‐free survival according to multivariate analysis. Conclusions: These results suggest that sialylated MUC1 plays an important role in the progression of prostate cancer, and that its expression level in the primary lesion is a useful marker for the prognoses of patients undergoing endocrine therapy.     

Prognostic value of cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44s in surgically treated patients with prostate cancer

PURPOSE: Molecular tissue markers may give the clinician additional information about patients with prostate cancer at risk for treatment failure after retropubic radical prostatectomy. We substantiate the prognostic value of 3 tissue markers, the cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44s, in addition to more conventional pathological prognosticators in an historical (before prostate specific antigen) cohort of patients with prostate cancer. MATERIALS AND METHODS: Representative tumor sections from 92 patients who underwent retropubic radical prostatectomy were immunohistochemically stained with antibodies against p27(kip1), MIB-1 (Ki-67) and CD44s, and assessed in a semiquantitative manner. Gleason score and pathological tumor stage were recorded. All variables were correlated with clinical progression and disease specific survival on univariate and multivariate analyses. RESULTS: On univariate analysis low (less than 50%) p27(kip1), high (10% or greater) MIB-1 and loss of CD44s expression were significantly associated with clinical outcome parameters, although MIB-1 did not reach statistical significance for disease specific survival. All 3 molecules were highly correlated with Gleason score and pathological tumor stage. Multivariate analysis showed that low p27kip1 was independent of grade and stage in predicting clinical recurrence (p <0.001) and disease specific survival (p = 0.045), while loss of CD44s was an additional independent prognostic factor for clinical recurrence (p = 0.02). CONCLUSIONS: Reduced p27(kip1) expression is an independent predictor of poor outcome in prostate cancer, while MIB-1 is not. Decreased expression of CD44s yields additional information in predicting clinical recurrence. These tissue markers may identify patients at risk for disease recurrence after retropubic radical prostatectomy who may benefit from adjuvant therapy.     

Changes in chromogranin a serum levels during endocrine therapy in metastatic prostate cancer patients

INTRODUCTION: The concept of neuroendocrine (NE) differentiation in prostate cancer has become more widely recognized as its diagnostic, prognostic, and therapeutic usefulness. PATIENTS AND METHODS: We enrolled 38 patients with stage D prostate cancer who underwent endocrine therapy by medical or surgical castration and oral antiandrogen. According to PSA response, serum levels of CGA as a marker of NE differentiation were measured at the multiple points of time; (1) pre-treatment, (2) complete response (CR), (3) a nadir level of PSA, (4) PSA failure or hormone independent progression. We compared these serum values in relation to efficacy of endocrine therapy. RESULTS: There was no correlation between serum PSA and CGA values. Patients consisted of 27 with CR and 11 without CR. Serum CGA increased as intervals of endocrine therapy became longer with positive correlation (p < 0.05). Its velocity was higher in patients with PSA failure than in those without it (6.98 vs. 2.09 ng/ml/month, p = 0.011). CONCLUSION: During endocrine therapy in metastatic prostate cancer patients, serum CGA values were not related to serum PSA levels, and increased as treatment periods became longer. It is suggested that CGA velocity has potential to predict androgen independent progression after endocrine therapy.     

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.     

Human epidermal growth factor receptor type 2 protein expression in Chinese metastatic prostate cancer patients correlates with cancer specific survival and increases after exposure to hormonal therapy

Aim： To investigate human epidermal growth factor receptor type 2 （HER2） protein expression and gene amplification in Chinese metastatic prostate cancer patients and their potential value as prognostic factors. Methods： Immunohistochemistry （IHC） was performed to investigate HER2 protein expression in prostate biopsy specimens from 104 Chinese metastatic prostate cancer patients. After 3-11 months of hormonal therapy, 12 patients underwent transurethral resection of the prostate （TURP）. HER2 protein expression of TURP specimens was compared with that of the original biopsy specimens. Of these, 10 biopsy and 4 TURP specimens with HER2 IHC staining scores ≥ 2＋ were investigated for HER2 gene amplification status by fluorescent in situ hybridization （FISH）. Results： Of the 104 prostate biopsy specimens, HER2 protein expression was 0, 1＋, 2＋ and 3＋ in 49 （47.1%）, 45 （43.3%）, 8 （7.7%） and 2 （1.9%） cases, respectively. There was a significant association between HER2 expression and Gleason score （P = 0.026）. HER2 protein expression of prostate cancer tissues increased in 33.3% of patients after hormonal therapy. None of the 14 specimens with HER2 IHC scores 〉 2＋ showed HER2 gene amplification. Patients with HER2 scores 〉 2＋ had a significantly higher chance of dying from prostate cancer than those with HER2 scores of 0 （P = 0.004） and 1＋ （P = 0.034）. Multivariate Cox regression analysis showed that HER2 protein expression intensity was an independent predictor of cancer-related death （P = 0.039）. Conclusion： An HER2 IHC score 〉 2＋ should be defined as HER2 protein overexpression in prostate cancer. Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer. HER2 protein expression increases in some individual patients after hormonal therapy.     

Pattern of progression and survival in hormonally treated metastatic prostate cancer

BACKGROUND: Patients with prostate cancer generally respond to androgen ablation therapy, but progression to androgen-independence is frequently observed. To further evaluate disease progression, the pattern of progression and survival in hormonally treated metastatic prostate cancer was examined. METHODS: One hundred and ninety-three patients with untreated metastatic prostate cancer (TxNxM ) who received endocrine therapy between 1986 and 1995 were included in the present study. The pattern of progression was evaluated in these patients. RESULTS: One hundred and eighteen of the 193 patients (61.1%) had disease progression: 33 had local progression, 73 had distant progression and 12 had distant with local progression. Patients with only local progression had a longer interval to disease progression and longer survival than those with distant progression. The interval from disease progression to death in patients with local progression was longer than in those with distant progression. The patients whose prostate-specific antigen (PSA) had not been normalized 3 months after the start of endocrine therapy had a tendency to progression either into the prostate or into distant sites. Patients with extent of disease (EOD) scores of 3 and 4 progress, especially to distant sites, after endocrine treatment. CONCLUSIONS: In untreated metastatic prostate cancer, patients with a poor response of PSA levels and patients with a high volume of bone metastasis (i.e. EOD 3, 4) were in the high-risk group for progression, especially to distant sites. Progression into distant sites was a poor prognostic factor for patients with recurrence to endocrine therapy.     

Prognostic significance of prostate specific antigen in endocrine treatment for prostatic cancer.

The prognostic value of prostate specific antigen was evaluated to predict disease progression after endocrine therapy in patients with prostatic cancer. A total of 73 patients was studied (6 with stage B2, 16 with stage C, 9 with stage D1 and 42 with stage D2 disease). Endocrine therapy included bilateral orchiectomy, diethylstilbestrol diphosphate and luteinizing hormone-releasing hormone analogue. Pre-treatment serum prostate specific antigen levels were determined in all patients with an enzyme immunoassay kit. During a followup of 4 to 68 months (average 24 months) clinical disease progression occurred in 24 of the 73 patients. The pre-treatment prostate specific antigen level by itself did not predict disease progression. Changes in prostate specific antigen level with treatment were correlated with the interval to disease progression in the 44 patients who had prostate specific antigen determinations at regular intervals after endocrine therapy and whose initial level was greater than 10 ng./ml. Patients who had a decrease in the prostate specific antigen levels of 80% or more within 1 month after the beginning of therapy survived significantly longer free of disease progression (p less than 0.001). Patients whose prostate specific antigen level remained elevated for more than 3 months had a high risk of disease progression within 2 years. Our study suggests that patients with the more favorable prognosis can be identified early, after 1 to 3 months of endocrine therapy, by the rapid decrease in the prostate specific antigen levels.     

Elevated serum progastrin-releasing peptide (31-98) level is a predictor of short response duration after hormonal therapy in metastatic prostate cancer

BACKGROUND: The neuroendocrine (NE) pathway has been attracting attention as a mechanism for the androgen-independent progression because the neuropeptide provokes tumor growth and inhibits apoptosis under androgen-deprived milieu in prostate cancer cells. On the basis that serum progastrin-releasing peptide (ProGRP) is elevated in patients with advanced disease stage, we examined the prognostic value of the neuropeptide. METHODS: Serum ProGRP status was determined with an enzyme-linked immunosorbent assay (ELISA) in 460 men with benign and malignant prostatic diseases, chronic renal failure, and healthy controls. Seventy patients with metastatic prostate cancer including four patients (5.7%) with NE carcinoma who underwent hormonal therapy were enrolled in the prognostic analyses by Cox proportional hazards model. RESULTS: The serum status steadily shifted toward predominant expression of ProGRP with the progression of prostate cancer into metastatic and androgen-independent stages. Univariate analysis revealed that the deteriorated performance status (PS) and extent of bony disease (EOD), and high serum alkaline phosphatase (ALP), serum ProGRP, and nadir prostate-specific antigen (PSA) levels were associated with a lower progression-free survival (PFS) rate (P < 0.005). Multivariate analysis demonstrated that PS, serum ProGRP, and nadir PSA held an independent predictive value for PFS (P < 0.05), and all correlated with bone-related factors. Serum ProGRP was the most significant predictor among pre-treatment factors in this model (P = 0.0094). CONCLUSIONS: The neuropeptide precursor ProGRP is a distinct serum marker that is useful to know the NE milieu and provides prognostic information in patients with advanced prostate cancer. Standard therapy for metastatic prostate cancer may make progress when further studies will clarify the causative link between serum ProGRP level and androgen-independent disease progression.     

The worst histologic elements predict prognosis in moderately-differentiated prostate cancer patients with androgen-withdrawal endocrine therapy.

OBJECTIVES: We evaluated the prognostic value of the worst histologic elements in 155 patients with moderately-differentiated prostate cancer (Gleason sum 5-7) treated with androgen-withdrawal endocrine therapy. METHODS: In individual cases, the proportion (%) of medullary/solid combined with columns-and-cords/trabecular (MED & C-C), regarded as the worst histologic elements, determined according to WHO-Mostofi's classification of histologic patterns, within the total adenocarcinoma area obtained from needle specimens was estimated. RESULTS: Patients with proportion of MED & C-C >5% had a significantly poorer prognosis than those with <5% (p < 0.05). A significant difference was also found in the survival curves of patients grouped by stage (p < 0.01). There was no significant difference among the patients with Gleason sum of 5, 6 and 7. Multivariate analysis showed that stage and MED & C-C had independent prognostic value. CONCLUSIONS: Proportion of MED & C-C may provide useful prognostic information about patients with moderately-differentiated, Gleason sum 5-7, prostate cancer treated with androgen-withdrawal endocrine therapy.     

High expression of PSM-E correlated with tumor grade in prostate cancer: a new alternatively spliced variant of prostate-specific membrane antigen

BACKGROUND: Prostate-specific membrane antigen (PSMA) overexpressed in prostate cancer (PCa) has been targeted for therapy and diagnosis of PCa. In the current study, PSMA cDNA was cloned from PCa tissue by RT-PCR. After sequencing, a new spliced variant of PSMA (PSM-E) was discovered and its specificity in PCa was evaluated. METHODS: PSM-E and PSMA mRNA were measured in LNCaP, PC-3 and prostate or nonprostatic malignancies. Following transfection of PC-3 with PSM-E cDNA in the pcDNA3.0 vector, PSM-E expression was measured by immunofluorescence and Western-blot. PSM-E and PSMA mRNA levels were quantified by a real-time PCR assay in normal prostate (n = 7), benign prostatic hyperplasia (BPH) (n = 22) and PCa (n = 41). The correlation between their levels and tumor grade was analyzed. RESULTS: PSM-E cDNA is identical to PSMA except for a 97-nucleotide region and a 93-nucleotide region. PSM-E and PSMA mRNA were detected in PCa and LNCaP, not in PC-3; PSMA could be detected in some nonprostatic tumors whereas PSM-E not. The expression of PSM-E protein was detected in transfected cells. Significant difference of PSM-E mRNA levels was observed among normal prostate, BPH and PCa (P < 0.001), and PSM-E levels increased with increasing Gleason score (r = 0.514, P < 0.001). PSMA mRNA levels were higher in BPH and PCa than in normal prostate (P < 0.001), but no difference between BPH and PCa, no significant correlation was observed between PSMA levels and Gleason score (r = 0.229, P = 0.057). CONCLUSIONS: PSM-E may be a potential prognostic indicator for PCa progression and may be a new target antigen for therapy of PCa.     

CAG polymorphic repeat lengths in androgen receptor gene among Japanese prostate cancer patients: potential predictor of prognosis after endocrine therapy

BACKGROUND: Several investigators have examined the clinical significance of the length of the CAG repeat at the N-terminal region of the androgen receptor in the pathogenesis of prostate cancer. Because the clinical significance of CAG repeat length during the course of prostate cancer in Japanese patients is unknown, the present study analyzed CAG repeat length in relation to several potential clinical factors. MATERIALS AND METHODS: A total of 88 Japanese patients with prostate cancer and a control group of 53 patients with benign prostatic disease were enrolled in this study. The length of the CAG repeat was determined by PCR sequencing and analyzed in relation to several clinical factors. RESULTS: The length of the CAG repeat did not significantly differ between prostate cancer and benign prostatic disease. Although not statistically different with regard to clinical stage and serum PSA level, the CAG repeat length was associated with histological grade and age at diagnosis. In addition, the CAG repeat length in CR and in non CR patients significantly differed at 22.1 +/- 2.4 and 24.4 +/- 3.0, respectively (P = 0.0264), suggesting that the CAG repeat length can act as a molecular marker with which to predict response to endocrine therapy in stage D prostate cancer patients. CONCLUSIONS: A shorter CAG repeat length appears to predict a response to endocrine therapy, showing a positive prognostic value and indicating good prognosis in the metastatic stage of prostate cancer patients.