The efficacy of a serum carboxyterminal pyridinoline cross-linked telopeptide of type I collagen as a quantitative screening marker for bone metastases in patients with urological malignancies

In order to ascertain whether carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) might be useful as a serum screening parameter for bone metastases from non-prostate urological malignancies as well as prostate cancers, as series of 210 patients were examined. In addition to ICTP, serum alkaline phosphatase (ALP) and also prostate specific antigen (PSA) in the prostate cancer cases were assayed using commercial kits. The areas under the receiver operating characteristic (ROC) curves were 0.7846 for ICTP (cut-off point 9.6 microg/l), 0.8304 for ALP in prostate cancer cases, and 0.8278 for ICTP (cut-off point 10.6 microg/l), and 0.7139 for ALP in non-prostate cancer cases. While significance was only observed for ICTP and PSA in prostate cancer cases, borderline significance was also evident with ICTP for non-prostate malignancies, and with ALP for prostate cancer case. The results suggest that serum ICTP may be useful in combination with ALP as a quantitative clinical marker for low cost screening for bone metastases in patients with all types of urological malignancies.     

Diagnosis of bone metastasis in men with prostate cancer by measurement of serum ICTP in combination with alkali phosphatase and prostate-specific antigen

AimsCarboxy-terminal telopeptide of type I collagen (ICTP) is a parameter of bone absorption, and has recently been introduced to monitor bone metastases. The aim of this retrospective study was to investigate the potential of ICTP as a candidate serum marker of bone metastasis in prostate cancer.Materials and methodsSerum markers in 155 men pathologically diagnosed with prostate cancer were measured. The serum levels of ICTP, prostate-specific antigen (PSA), and alkali phosphatase (ALP) were compared to assess the extent of disease (EOD) scores from bone scans and then analysed statistically.ResultsThe serum ICTP levels were not well correlated with the EOD scores in the total group of men, men newly diagnosed with prostate cancer, or men previously diagnosed with prostate cancer who were followed up. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of ICTP (cut-off value, 5.0 ng/ml) of the men newly diagnosed with prostate cancer were 78.6%, 88.0%, 78.6%, and 88.0%, respectively. In these men, the specificity and PPV of ALP (cut-off value, 335 IU/l) were 100%, whereas the sensitivity and NPV of PSA (cut-off value, 40 ng/ml) were 100% in this study. The serum levels of ICTP in the men with low ALP (<335 IU/l) and high PSA (≥40 ng/ml) clearly separated the men with or without bone metastasis, as judged by bone scans.ConclusionWe found that the ICTP is not a superior serum marker for bone metastases compared with ALP or PSA. Our study suggests, however, that the ICTP measurement is useful in a certain subset of men with the combination of PSA and ALP in distinguishing men with bone metastasis from those without.     

Type I collagen degradation product (ICTP) gives information about the nature of bone metastases and has prognostic value in prostate cancer.

Although osteosclerotic bone metastases are characteristic of prostate cancer, mixed metastases with a lytic component are not uncommon. Type I collagen is synthesised by osteoblasts and accounts for about 90% of the organic matrix of bone. We have used new specific immunoassays for PICP (carboxy-terminal propeptide of type I procollagen) and ICTP (cross-linked carboxy-terminal telopeptide of type I collagen) which allow simultaneous assessment of the synthesis and degradation of type I collagen respectively. Forty patients with bone metastases due to prostate cancer at the time of diagnosis were investigated with these methods. Twenty-three of them had sclerotic (S) and 17 had mixed metastases with sclerotic and lytic components (S + L) as assessed by radiographs. The concentrations of PICP and ICTP in serum as well as the activity of alkaline phosphatase (AP) were increased in all patients of the S + L group, who had more aggressive bone disease and a shorter survival than the S group (P < 0.017). The ICTP level was above the reference range in half of the patients in the S group, whereas the PICP and AP levels were elevated in 35%. Of the bone markers, only ICTP was of prognostic significance (P < .05). We conclude that ICTP and PICP give information about the type and activity of the skeletal metastases. In addition, ICTP predicts prognosis.     

Evaluation of bone metabolic markers in breast cancer with bone metastasis

PURPOSE: In the present study, four bone metabolic markers were examined to clarify them meaning and clinical value in the detection of bone metastasis (BM) from breast cancer. METHODS: we examined serum carboxyterminal telopeptide of type I collagen (ICTP), tartrate resistant acid phosphatase (TRACP), total alkaline phosphatase (ALP) and urinary type I collagen cross-linked N-telopeptides (NTx) as potential markers. These bone markers were evaluated simultaneously in 156 breast cancer patients; 114 patients without metastasis (group A), 23 patients with BM (group B) and 19 patients with metastasis at sites other than bone (group C). RESULTS: The mean values of ICTP and TRACP in group B were significantly greater than those in group A. Group B consisted of the patients with varying degrees of BM and variation in their treatments. The patients in group B were divided into BM (+) and BM (++) according to hot spots in bone scan. ICTP and TRACP were elevated in BM (++) patients compared to BM (+) patients (p<0.05). The values of ICTP and TRACP of the twelve patients without treatment in group B were significantly higher than those in group A. In the treated patients of group B, the mean values of ICTP and TRACP were lower in responders and cases of stable disease than those with progression. NTx and ALP were inferior to ICTP and TRACP for clinical evaluation of BM. CONCLUSIONS: We confirmed that ICTP and TRACP might be useful markers for screening and monitoring BM in breast cancer.     

ICTP在诊断乳腺癌骨转移中的临床价值

目的：探讨ICTP在诊断乳腺癌骨转移中的临床价值。方法：用EIA法测定60例乳腺癌患者和23例健康体检者的ICTP血清水平。结果：乳腺癌骨转移患者ICTP血清水平较非骨转移和正常对照组显著升高,其诊断敏感性为77.8%,特异性为91.3%。多处骨转移患者血清ICTP阳性率和血清水平较单处骨转移患者显著升高且随着乳腺癌分期的升高,血清ICTP阳性率和血清水平也升高。结论：ICTP对乳腺癌骨转移患者的早期诊断,病情监测和临床分期判断具有重要意义。     

Markers of bone turnover for the management of patients with bone metastases from prostate cancer

Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to that of bone formation in patients with bone metastases from prostate cancer before and after bisphosphonate treatment. Thirty-nine patients with prostate cancer and bone metastasis, nine patients with prostate cancer without bone metastases, nine patients with benign prostatic hyperplasia and 355 healthy age-matched men were included. Urinary non-isomerized (alpha CTX) and beta isomerized (beta CTX) type I collagen C-telopeptides (CTX) and a new assay for serum CTX were used to assess bone resorption. Bone formation was determined by serum osteocalcin, serum total (T-ALP) and bone (BAP) alkaline phosphatase and serum type I collagen C-terminal propeptide (PICP). Fourteen patients with bone metastases were also evaluated 15 days after a single injection of the bisphosphonate pamidronate (120 mg). Levels of all bone formation and bone resorption markers were significantly (P < 0.006-0.0001) higher in patients with prostate cancer and bone metastasis than in patients with benign prostatic hyperplasia, patients with prostate cancer without bone metastases and healthy controls. In patients with bone metastases the median was increased by 67% for serum osteocalcin, 128% for T-ALP, 138% for BAP, 79% for PICP, 220% for urinary alpha CTX, 149% for urinary beta CTX and 214% for serum CTX. After bisphosphonate treatment all three resorption markers significantly decreased by an average of 65% (P = 0.001), 71% (P = 0.0010) and 61% (P = 0.0015) for urinary alpha CTX, urinary beta CTX and serum CTX, respectively, whereas no significant change was observed for any bone formation markers. Patients with prostate cancer and bone metastases exhibit a marked increase in bone resorption, which decreases within a few days of treatment with pamidronate. These findings suggest that these new resorption markers may be useful for the management of these patients.     

Serum concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a useful prognostic indicator in multiple myeloma.

Type I collagen is the main collagen type found in mineralised bone. Specific immunoassays for PICP (carboxyterminal propeptide of type I procollagen) and ICTP (cross-linked carboxyterminal telopeptide region of type I collagen) allow simultaneous assessment of the synthesis and degradation of type I collagen in serum samples, respectively. Our aim was to find out whether these metabolites of type I collagen are useful markers for following bone turnover and evaluating treatment response in multiple myeloma, which is a good model disease of excessive osteolysis. Fifteen consecutive patients were studied before and throughout their treatment. Samples for serum PICP and ICTP were collected before starting each treatment course of melphalan and prednisolon. Response to treatment was evaluated by following the changes in M protein and bone roentgenograms. The disease was progressing in four and regressive in 11 patients, but in four of these a recurrence occurred. In nonresponders the ICTP concentration was permanently elevated despite treatment. In responders both increased or normal levels of ICTP were initially observed, but they returned to or remained in the reference interval during treatment. The ICTP concentration increased upon recurring disease. There was a strong correlation between the extent of bone lesions and ICTP. There was no correlation between ICTP and PICP, the latter mainly remaining within the reference range, a finding that suggests no change in bone formation. ICTP was a significant predictor for survival in this patient group (P less than 0.05). We conclude that ICTP is a specific and sensitive marker for bone resorption. Simultaneous use of serum ICTP and PICP offers an additional and easy means to follow bone turnover and evaluate the response to therapy in multiple myeloma.     

血清缓激肽与前列腺癌的相关性研究

目的 探讨血清缓激肽在前列腺癌的诊断及鉴别诊断中的临床应用价值.方法 收集68例前列腺癌患者和32例前列腺增生患者,以同期体检的健康男性32例为对照组,收集其血清,酶联免疫吸附试验(enzymelinked immuno sorbent assay,ELISA)法检测血清中的缓激肽水平,比较各组血清缓激肽水平的差异以及前列腺癌患者在不同年龄、临床分期、病理分期(Gleason评分)、前列腺特异抗原(prostate specific antigen,PSA)水平、肿瘤体积以及骨转移、淋巴结转移、局部侵犯与否状态下血清缓激肽水平的差异.比较血清缓激肽与PSA联合诊断前列腺癌和PSA独立诊断前列腺癌的敏感度差异.结果 前列腺癌组血清缓激肽水平[(16.44 ±0.91) μg/L]低于对照组[(19.72±1.10) μg/L]和前列腺增生组[(20.93±1.80) μg/L],差异均具有统计学意义(均P＜0.05).在肿瘤体积较大的前列腺癌患者血清缓激肽水平较低(P＜0.05),而血清缓激肽水平在年龄、肿瘤临床分期、病理分期(Gleason评分)、PSA水平及骨转移、淋巴结转移、局部侵犯与否方面比较差异均无统计学意义(均P＞0.05).血清缓激肽与PSA联合诊断前列腺癌较单独诊断敏感度提高(P＜0.05).结论 前列腺癌患者血清缓激肽表达水平较低,且与肿瘤体积相关.血清缓激肽与PSA联合诊断前列腺癌敏感度较单独诊断高.     

Markers of type I collagen degradation and synthesis in the monitoring of treatment response in bone metastases from breast carcinoma.

Thirty-six patients with bone metastases included in a trial of supportive calcitonin on the treatment response to systemic therapy were monitored by conventional radiography, conventional indicators of bone metabolism [alkaline phosphatase (AP), osteocalcin (gla), urinary hydroxyproline excretion (OHP), urinary calcium (uCa), serum calcium (sCa)] and collagen metabolites (ICTP, the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen; PICP, the carboxy-terminal propeptide of type I procollagen; and PIIINP the amino-terminal propeptide of type III procollagen). All patients had been on the same systemic treatment for at least 3 months at the start of the trial. There was a positive correlation between the concentrations of ICTP and PICP at baseline (Spearman''s rank-order correlation coefficient rs = 0.62). Both ICTP and PICP showed statistically significant correlations to the other markers of bone metabolism (except sCa and uCa) as well as to the number of bone metastases on bone scans. Reduction in ICTP correlated significantly with the treatment response at three months (rs = - 0.57). while PICP showed a borderline negative correlation to therapy response (rs = - 0.37). Of all the biochemical parameters studied the changes in ICTP showed the best correlation with the treatment response. PICP and ICTP changes in patients with progressive disease differed significantly from those in patients with responding and stable metastases, whereas no difference was found between responders and stable patients.     

血清ICTP、ALP联合测定对骨肿瘤的诊断价值

目的：探讨血清Ⅰ型胶原羧基吡啶末端肽（ICTP）及碱性磷酸酶（ALP）联合测定对骨肿瘤的诊断价值。方法：采用酶联免疫吸附试验（ELISA）和化学连续监测法测定骨肿瘤患者血清ICTP与ALP的水平。结果：恶性骨肿瘤患者血清ICTP、ALP水平明显高于良性骨肿瘤患者及正常对照组，P〈0．01。ICTP和ALP对骨肿瘤的敏感性分别为78．9％，57．9％；特异性分别为85．1％，74．5％。经受试者工作特征曲线（ROC）分析，并联试验测定的特异性为80．9％，敏感性为89．5％，与单项测定指标相比，其敏感性相差显著，P〈0．01。结论：血清ICTP与ALP联合检测对于骨肿瘤的诊断具有较高的应用价值。     

Serum concentration of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen in patients with metastatic breast cancer

The serum concentration of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) was examined in 83 patients with metastatic breast cancer. ICTP levels were significantly higher in patients with bone metastases than in those without bone metastasis. In patients with bone metastasis, significantly higher ICTP levels were observed in those with multiple lesions than in those with a solitary lesion and these levels reflected therapeutic response. Sequential monitoring of ICTP revealed that this elevation was correlated with disease progression. Combined with imaging studies, monitoring of ICTP appears to offer additional information for detection of bone metastasis and evaluation of therapeutic response to bone metastasis.     

肺癌患者血清ＮＴｘ、ＩＣＴＰ和ＢＡＰ水平与骨转移的相关性研究

目的　探讨联合检测骨代谢生化指标血清Ⅰ型胶原氨基末端肽（ＮＴｘ）、Ⅰ型胶原羧基端肽（ＩＣＴＰ）及骨特异性碱性磷酸酶（ＢＡＰ）对诊断肺癌骨转移的临床意义。方法　选择经细胞学和病理学确诊的肺癌患者１０６例,分为两组,其中骨转移组６１例,无骨转移组４５例。用ＥＬＩＳＡ法检测两组患者血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ浓度。结果　骨转移组患者血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平分别为（２５.３６±１１.０７）ｎｍｏｌ／Ｌ、（２９.１８±１０.７４）μｇ／Ｌ和（７８.３１±１６.５３）μｇ／Ｌ,明显高于无骨转移组的（１２.１６±７.６２）ｎｍｏｌ／Ｌ、（１１.０２±５.３２）μｇ／Ｌ和（２４.０１±７.９８）μｇ／Ｌ,差异具有统计学意义（Ｐ＜０.０１）;ＮＴｘ、ＢＡＰ、ＩＣＴＰ诊断骨转移的灵敏度和特异度分别为９０.１６％和８４.４４％、８０.３２％和７７.７８％、７０.４９％和９１.１１％;多发骨转移组患者血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平明显高于单发骨转移组（Ｐ＜０.０５）;骨转移组患者血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平与疼痛程度呈正相关;不同性别、病理类型、转移部位患者的血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平差异无显著性（Ｐ＞０.０５）。结论　血清ＮＴｘ、ＩＣＴＰ及ＢＡＰ水平对肺癌骨转移诊断的灵敏度和特异度较高,与骨转移数目和疼痛程度相关,是诊断肺癌骨转移的重要参考指标。     

Biochemical markers of bone turnover in breast cancer patients with bone metastases: a preliminary report

BACKGROUND: Some biochemical markers of bone turnover are expected to reflect the disease activity of metastatic bone tumor. In the present study six biochemical markers were evaluated to determine appropriate markers for the detection of metastatic bone tumors from breast cancer (BC). METHODS: A panel of bone turnover markers was assessed in 11 normocalcemic patients with bone metastases from BC and in 19 BC patients without clinical evidence of bone metastases. Bone formation was investigated by measuring serum bone isoenzyme of alkaline phosphatase (BALP), osteocalcin (OC) and carboxy-terminal propeptide of type I procollagen (PICP): Bone resorption was investigated by measuring serum carboxy-terminal telopeptide of type I collagen (ICTP), fasting urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr). RESULTS: PICP was influenced by age and menopausal status. Significant correlations were observed between each of bone turnover markers except between BALP and OC. The mean levels of the six bone turnover markers were higher in patients with bone metastases than in those without them and significance was observed except for OC. The best diagnostic efficiency by receiver-operating characteristic (ROC) analysis was provided by ICTP followed by Pyr or D-Pyr, BALP, PICP and OC and significance was observed between ICTP and OC. Multiple logistic regression analysis adjusted by age revealed that the only significant marker related to bone metastases was ICTP. CONCLUSIONS: Serum ICTP appears to be the leading marker of bone metastases from BC. However, to reveal the clinical usefulness of these markers, further examination will be needed to account for the ease and cost-effectiveness of the measurements.     

Usefulness of bone metabolic markers in the diagnosis and follow-up of bone metastasis from lung cancer.

Ninety-one lung cancer patients were evaluated to determine the usefulness of bone metabolic markers in the diagnosis and follow-up of bone metastases and also to investigate their clinical usefulness as an adjunct to bone scintigraphy. Both bone resorption markers, ICTP and fDPD, and bone formation markers, Al-p, BAL, PICP and BGP, were evaluated in 47 patients with and 44 without bone metastasis. The patients with bone metastasis were classified according to the bone metastatic burden, and they were also separately classified into groups according to the course of the bone metastasis. ICTP, fDPD, Al-p and BAL were significantly elevated (P < 0.001) in patients with bone metastasis, but PICP and BGP were not. Receiver-operating characteristic (ROC) curves of these markers revealed that ICTP was most highly correlated with the diagnosis of bone metastasis. The sensitivity of ICTP (71.4%) and fDPD (61.0%) were good with high specificity. T scores of ICTP, fDPD and BAL tended to be higher at higher grades of bone metastasis. T-scores of ICTP, fDPD and BAL were elevated in the newly diagnosed cases and progressed cases, but the T-scores of ICTP and fDPD in those cases were higher than that of BAL. In the follow-up study, ICTP was well correlated with uncontrolled or controlled bone metastasis. Thus, bone resorption markers, especially ICTP, could be a good indicator of the progression and multiplicity of disease, and it could help in the follow-up and in the monitoring of therapy for bone metastasis from lung cancer.     

Usefulness of serum carboxy-terminal telopeptide of type I collagen (ICTP) as a marker of bone metastasis from lung cancer

BACKGROUND: Serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) is a metabolite of type I collagen comprising 90% or more of organic substances in bone. Its usefulness as a marker of bone metastasis from malignant tumors is expected. METHOD: We measured ICTP to evaluate its clinical usefulness for diagnosis of bone metastasis in 140 patients with lung cancer. For comparison, serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1), gastrin-releasing peptide precursor (ProGRP), alkaline phosphatase and calcium were simultaneously measured. ICTP was measured by double-antibody radioimmunoassay. RESULTS: ICTP was significantly higher in patients with bone metastasis from lung cancer than in the group without bone metastasis, patients with other pulmonary diseases or healthy control subjects and showed excellent sensitivity and specificity, indicating that this marker is highly useful for complementary diagnosis of bone metastasis from lung cancer. Moreover, the survival duration was significantly shorter in the ICTP-positive group than in the ICTP-negative group, suggesting that ICTP can be a prognostic factor in lung cancer. CONCLUSION: It is suggested that measurement of ICTP is worthwhile as a serological diagnostic method of bone metastasis from lung cancer. Moreover, since repeated measurements are possible, this measure was considered very helpful in complementary diagnosis of bone metastasis and also as a standard to determine the timing of examinations such as bone scintigraphy.     

血清骨特异性碱性磷酸酶及Ⅰ型胶原吡啶交联终肽与乳腺癌骨转移的相关性分析

 目的　分析血清骨特异性碱性磷酸酶（BAP）和Ⅰ型胶原吡啶交联终肽（ICTP）水平在乳腺癌骨转移与非骨转移患者中的分布及其与临床特征的相关性。方法　收集乳腺癌患者血清217例，通过影像学将患者分为骨转移组（109例）和非骨转移组（108例）。应用酶联免疫吸附法测定两组血清中的BAP及ICTP水平。结果　乳腺癌骨转移组血清BAP及ICTP水平中位数分别为24.8 μg／L（7.6~213.7 μg／L）和7.0 μg／L（1.4~32.4 μg／L），高于非骨转移组的21.2 μg／L（7.3～68.8 μg／L）和4.1 μg／L（0.0～15.8 μg／L）（P＝0.003和P＝0.000），多发骨转移组的BAP及ICTP水平中位数分别为32.3 μg／L（9.4~213.7 μg／L）和7.6 μg／L（1.4～32.4 μg／L），高于单发骨转移组的18.1 μg／L（7.6～60.0 μg／L）和4.9 μg／L（1.8～10.5 μg／L）（P＝0.001和P＝0.010）。血清BAP检测诊断乳腺癌骨转移的灵敏度为45.0 %（49／109），特异度为83.3 %（90／108）；血清ICTP的灵敏度为46.8 %（51／109），特异度为84.3 %（91／108）；两者联合检测的灵敏度为61.5 %（67／109），特异度为71.3 %（77／108）。结论　检测血清BAP及ICTP诊断乳腺癌骨转移的灵敏度较低，不适合作为诊断指标。两者联合检测可以提高灵敏度，对辅助诊断有一定价值。     

血清ICTP、PICP、PINP的检测对原发性肝癌骨转移的诊断意义

为了研究血清ＩＣＴＰ、ＰＩＣＰ和ＰＩＩＮＰ的水平与原发性肝癌骨转移的关系，采用放射免疫法检测了５０例原发性肝癌（骨转移３０例，无骨转移２０例）及２０例健康者血清中ＩＣＴＰ、ＰＩＣＰ和ＰＩＮＰ的水平，结果发现，原发性肝癌患者血清ＩＣＴＰ、ＰＩＮＰ显著高于健康者（Ｐ＜０．０１和Ｐ＜０．０５），其中伴骨转移的原发性肝癌血清ＩＣＴＰ、ＰＩＮＰ显著高于无骨转移者（Ｐ＜０．０１），但ＰＩＣＰ则无显著性差异，提示ＩＣＴＰ和ＰＩＮＰ可作为原发性肝癌的预后判断指标，尤其可作为原发性肝癌发生骨转移的判断指标。     

Dissociation of bone formation markers in bone metastasis of prostate cancer.

To clarify the meaning and clinical value of bone formation markers in bone metastasis from prostate cancer, we investigated the bone formation markers carboxy-terminal propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BA1-p) and osteocalcin, so-called bone gla protein (BGP) in 43 prostate cancer patients with and 46 patients without overt bone metastasis. Patients with bone metastasis were evaluated repeatedly by bone scan at intervals of 3-6 months. The expression patterns of bone formation markers in patients with progression of bone metastasis became dissociated; BA1-p and PICP were elevated in patients with progression of bone metastasis but BGP was not. Instead, BGP showed slight elevation in patients with improvement and complete remission of bone metastasis. PICP, BA1-p and BGP are all bone formation markers, but each marker appears in a different phase of bone formation: PICP appears in proliferation phase, BA1-p appears in matrix maturation phase and BGP appears in late bone formation phase. Our findings that BGP was not elevated in progression of bone metastasis and that it increased slightly with improvement and complete remission of bone metastasis may imply that the bone formation that occurs in blastic bone metastasis is different from normal bone formation.     

Serum interleukin 6 as a prognostic factor in patients with prostate cancer.

The present study was undertaken to evaluate the prognostic significance of the serum levels of interleukin 6 (IL-6) in patients with prostate cancer. Serum IL-6 levels were measured in 74 patients with prostate cancer. The tumor was stage B in 23 patients, stage C in 14 patients, and stage D in 37 patients. Prognostic significance of tumor histology, performance status (PS), bone metastasis, serum prostate-specific antigen (PSA) level, serum alkaline phosphatase (ALP) level, serum lactate dehydrogenase level, serum IL-6 levels, and hemoglobin on disease-specific survival was assessed using univariate and multivariate Cox's proportional hazards model analyses. Serum IL-6 was significantly correlated with the clinical stage of prostate cancer. Univariate analysis of all patients demonstrated that an extent of disease (EOD) on bone scanning > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, and ALP > 620 IU/liter were associated with a significantly lower survival rate than their respective counterparts. In multivariate analysis, however, the only two significant prognostic factors were EOD and IL-6. In 51 patients with stage C and stage D prostate cancer, univariate analysis showed that EOD > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, LDH > 200 IU/liter, and ALP > 620 IU/liter were significantly related to survival, whereas multivariate analysis again demonstrated that EOD > or = 1 and IL-6 > or = 7 pg/ml were significant prognostic factors. These results indicate that the serum IL-6 level is a significant prognostic factor for prostate cancer as well as EOD.     

Serum soluble Fas level for detection and staging of prostate cancer

To evaluate the clinical usefulness of measuring serum soluble Fas (sFas) for differentiation between prostate cancer and benign prostate hyperplasia (BPH) and for staging of prostate cancer, serum sFas and PSA were determined in 38 and 20 men with prostate cancer and BPH, respectively, before treatment. In 17 patients, sFas and PSA were measured one hour after transrectal ultrasound-guided sextant biopsy in order to examine the leakage of sFas into the circulation after prostatic injury. Patients with prostate cancer had a significantly higher level of sFas than those with BPH. The serum sFas level was statistically elevated in patients with metastatic prostate cancer. There was a statistically significant correlation between sFas and PSA in patients with prostate cancer but not in those without cancer. The serum sFas did not change one hour after systematic prostatic biopsy although PSA levels were markedly elevated. sFas levels might be useful as a discriminator between prostate cancer and BPH while sFas might indicate the tumor burden in patients with prostate cancer.