Clinical studies of a fast homoarginine-sensitive alkaline phosphatase in patients with cancer

The activity of an isoenzyme of alkaline phosphatase (FHAP) was measured in serum samples obtained from 1692 individual subjects. The median FHAP concentration in patients with untreated or recurrent cancer (2.73 IU/liter) was two-fold higher than in hospitalized control patients with illnesses other than cancer (1.17 IU/liter) and three-fold higher than in healthy control subjects (0.93 IU/liter). Among patients with either breast or colorectal cancer who were clinically disease free following their initial therapy, the median FHAP concentration (1.54 IU/liter) was intermediate between the median FHAP concentration in patients with untreated or recurrent cancer and that of healthy control subjects. In order to illustrate the potential clinical application of FHAP as a diagnostic cancer marker, we have selected a serum FHAP concentration of 2.22 IU/liter as a reference value above which only 3% of healthy control subjects would have a "positive" test. Utilizing this reference value, 58% of the patients in the present study with untreated or recurrent cancer would have a positive FHAP test, whereas only 11%, of hospitalized patients with illnesses other than cancer would have a positive test. These data suggest that FHAP may be equivalent to the carcinoembryonic antigen as a diagnostic cancer marker.     

Significance of a new stratification of alkaline phosphatase and extent of disease in patients with prostate carcinoma with bone metastasis.

Bone is the most frequent site of metastatic prostate cancer and the prognosis of patients with bone metastasis is poor. The authors have investigated a semiquantitative system to evaluate bone metastatic lesions in terms of cancer-specific survival. Based on the extension of disease (EOD) grade proposed by Soloway and associates, a new EOD grading system obtained from bone scintigraphy alone and EOD score obtained from bone scintigraphy and alkaline phosphatase was studied in 164 patients with prostate cancer with metastatic bone involvement. In terms of a cancer-specific survival and prostate cancer death, both the new EOD grade and the EOD score were apparently superior to eight other items studied (age, medical score, gait disturbance, histologic grade, erythrocyte sedimentation rate, prostatic acid phosphatase, and alkaline phosphatase). Multivariate analysis revealed that the EOD score was better than the new EOD grade. This improvement was due to the elimination of false-positive or nonactive metastatic bone lesions on bone scintigraphy through the alkaline phosphatase evaluation.     

Significance of alkaline phosphatase isozymes in the monitoring of patients with colorectal carcinoma

The clinical course of colorectal carcinoma may be monitored by tumor markers such as carcinoembryonic antigen (CEA), carcinoma antigen (CA) 19-9 and CA-50. Alkaline phosphatase isozymes were previously used to study the clinical course of testicular and gynecologic tumors. In this study we investigated 8 patients with advanced colorectal carcinoma. Their sera were analyzed for the tumor markers CEA, CA 19-9, CA-50 and three alkaline phosphatase isozymes: the nonspecific liver isozyme LAP, the intestinal isozyme IAP and the placental isozyme PLAP. Rising levels of CEA, CA 19-9 and CA-50 were seen as expected, and PLAP also showed rising levels during tumor progression. LAP remained elevated. This indicates an association between progression of colorectal carcinoma and a raised serum content of alkaline phosphatase isozymes.     

血清骨型碱性磷酸酶对于恶性肿瘤骨转移的诊断价值

目的　探讨血清骨型碱性磷酸酶（-ＡＬＰ）对恶性肿瘤骨转移的诊断价值。方法　８３例恶性肿瘤患者按照有无骨转移分为骨转移组和无骨转移组,分别行骨显像检查并测定血清ＡＬＰ、Ｂ-ＡＬＰ水平。对骨转移组和无骨转移组以及骨显像不同级别者的血清ＡＬＰ、Ｂ-ＡＬＰ水平进行比较。结果　（１）在８３例患者中,骨转移者４３例、无骨转移者４０例,转移率５１.８１％。（２）骨转移组血清ＡＬＰ水平为（１４０.４８８±１０５.２６５）Ｕ／Ｌ,与无骨转移组的（８８.０７５±２７.２００）Ｕ／Ｌ相比,差异显著（Ｐ＝０.０００）,骨转移组血清Ｂ-ＡＬＰ水平为（１５２.３２６±４０.３９０）Ｕ／Ｌ,与无骨转移组的（１０７.５±１５.１９１）Ｕ／Ｌ相比,差异显著（Ｐ＝０.０００）。骨显像０～３级各组Ｂ-ＡＬＰ分别为（１０８.１０８±１５.６５０）、（１１１.３６４±１３.０５６）、（１３５.４１７±１２７.０９１）和（１７１.７３９±４２.１７４）Ｕ／Ｌ,除０级组与１级组、１级组与２级组之间Ｂ ＡＬＰ值无差异外,其它各组间的差异显著（Ｐ＜０.０５）。（３）在诊断的敏感度和特异度的比较中,骨显像诊断的敏感度最高,可以达到９５.４％,但其特异度最低８７.５％;而骨显像＋Ｂ-ＡＬＰ敏感度为５３.５％,但特异度达到１００.０％。结论　同时测定血清Ｂ-ＡＬＰ有助于明确恶性肿瘤患者核素骨显像异常表现的病变性质,骨显像联合Ｂ-ＡＬＰ检测可以提高诊断特异度。血清Ｂ-ＡＬＰ对恶性肿瘤骨转移诊断及肿瘤骨转移的病情判断有一定临床应用价值。     

Evaluation of the value of fluorometric serum heat stable alkaline phosphatase assay in patients operated on for ovarian tumors

The usefulness of a simple fluorometric assay for serum heat-stable alkaline phosphatase (HSAP) in the diagnosis and follow-up of ovarian cancer patients was evaluated. 50 percent of the patients with malignant ovarian tumors had serum HSAP-activities above the upper reference range. Active production of this tumor marker in malignant but not in benign ovarian tumors was demonstrated by analysing serum HSAP-activities in ovarian vein blood. After operation, serum HSAP-activities decreased in all cancer patients with elevated preoperative values. Our results suggest that fluorometric serum HSAP-assay may be a useful alternative method for the determination of this tumor marker especially in a clinical laboratory.     

骨碱性磷酸酶同工酶在乳腺癌骨转移诊断中的应用

目的：探讨骨碱性磷酸酶（ALP）同工酶与乳腺癌骨转移的相关性。方法：采用琼脂糖电泳法分析测定60名健康体检者和108例乳腺癌患者血清中的 ALP 同工酶。结果：乳腺癌组的总 ALP 和同工酶均高于正常对照组,乳腺癌骨转移组的总 ALP 和骨 ALP 活性均显著高于对照组和无骨转移组,乳腺癌无骨转移组的总ALP 和骨 ALP 活性和对照组无显著性差异。结论：骨 ALP 与乳腺癌骨转移有一定的相关性,琼脂糖电泳法分离 ALP 同工酶有助于临床辅助诊断乳腺癌有无骨转移。     

CA125 and placental alkaline phosphatase as serum tumor markers in epithelial ovarian carcinoma.

Placental alkaline phosphatase (PLAP) was measured by an immunoradiometric assay using the monoclonal antibody C2 (PLAP-C2). Serum samples of 135 patients with epithelial ovarian cancer were analyzed, and the results were compared with CA125 levels. CA125 and PLAP-C2 were elevated in 85 and 43% of the patients, respectively. Only 1 patient with normal CA125 and evidence of disease at the time of sampling had an elevated PLAP-C2. Fifty-three patients with measurable tumor were followed longitudinally during chemotherapy. Correct correlation with disease evolution was observed in 95% of the patients for CA125 and in 59% for PLAP-C2. The PLAP-C2 assay did not add significantly to the predictive value of CA125 in the diagnosis and follow-up of epithelial ovarian cancer.     

碱性磷酸酶和淋巴细胞比值在评估BCLC分级A-B级肝癌患者TACE术后生存情况的应用价值

目的:探讨碱性磷酸酶和淋巴细胞比值(ALR)在预测巴塞罗那（BCLC）分级A-B级肝癌患者肝动脉灌注化疗栓塞术（TACE）术后生存情况的价值。方法:以肝癌TACE术后肿瘤进展或死亡为状态变量,分别以中性粒细胞和淋巴细胞比值、淋巴细胞和单核细胞比值、碱性磷酸酶、淋巴细胞计数以及ALR作为检验变量,进行两者的ROC分析,根据术前ALR预测肝癌患者TACE术后肿瘤进展或死亡的最佳诊断截点将所有纳入患者分为A组和B组,对两组肝癌患者通过倾向性评分匹配法进行配对分组,通过logistic回归估计倾向性评分值,检验匹配后两组临床病理指标的均衡性,匹配后标准差异绝对值均控制在 0.10以内,Kaplan-Meier生存分析分别比较匹配后A组和B组两组肝癌患者TACE术后无进展生存率和总生存率,采用Cox 回归分析评价匹配前后ALR对肝癌患者TACE术后PFS和OS的预测价值。结果:根据ALR最佳诊断截点将纳入所有患者分为ALR<5.4×10-7(A组)和ALR≥5.4×10-7(B组),通过倾向性评分匹配,两组共 57对匹配成功,匹配前两组间有显著性差异的临床指标经匹配后均达到平衡,其他无显著性差异的指标均衡性也得到了明显的提高,Kaplan-Meier生存分析显示,匹配后A组肝癌患者TACE术后1年、2年、3年无进展生存率显著高于B组(60.5%、41.2%、33.6% vs 47.9%、20.9%、20.9%,P＜0.05),A组肝癌患者TACE术后1年、2年、3年总生存率显著高于B组(72.3%、62.4%、55.2% vs 63.5%、51.5%、31.8%,P＜0.05),Cox回归分析显示,匹配前后ALR均为肝癌患者TACE术后PFS和OS的独立预测因素。结论:术前ALR水平预测BCLC分级A-B级肝癌患者TACE术后远期生存情况具有较高的价值。     

Serum N-telopeptide of type I collagen and bone alkaline phosphatase and their relationship in patients with non-small cell lung carcinoma and bone metastases. Preliminary results

Lung cancer represents the most common malignancy in Western countries and the presence of bone metastasis (BMs) may significantly worsen the prognosis. Several urinary and serum markers are altered in patients with BMs from non-small cell lung cancer (NSCLC). The aim of this study was to assess the usefulness of two serum markers of bone remodeling in patients with NSCLC and BMs. Thirty-five patients (24 men, 11 women, median age 63 years, range 51-72 years) with NSCLC were examined. There were 16 patients with confirmed BMs (Group A), and 19 age-matched (63.5±4.9 vs. 63.7±4.4 years; p=0.88) patients without BMs (Group B). Serum levels of bone resorption marker cross-linked amino-terminal telopeptide of type I collegen (NTx), and bone formation marker bone alkaline phosphatase (BAP) were measured in both groups by enzyme-linked immunosorbent assay. Both NTx (33.5±7.2 vs. 25.6±3.1 nM bone collagen equivalent, BCE/l) and BAP (51.7±6.0 vs. 40.7±7.3 U/l) serum levels were significantly (p<0.001) different between groups (A vs. B). Using a cut-off value of 30 nM BCE/l (TNx) and 50 U/l (BAP), the sensitivity was 56.2% and 37.5%, respectively (Odds ratio, OR=0.47, 95% confidence interval, CI 0.11-1.91, p=0.48), while the specificity was 89.5% and 84.2% (OR=0.62, 95% CI 0.09-4.26, p=0.50), respectively. No correlation was found between age and both NTx (R=-0.34, p=0.08) and BAP (R=-0.10, p=0.61) among patients with BMs. In conclusion, in patients with NSCLC and BMs both NTx and BAP are specific markers of bone remodeling, but their usefulness is limited in early diagnosis of metastatic disease.     

血清碱性磷酸酶、癌胚抗原、糖类抗原19-9联合检测对胃癌骨转移的诊断价值

目的探讨碱性磷酸酶(ALP)、癌胚抗原(CEA)、糖类抗原19-9(CA19-9)单独与联合检测对胃癌骨转移的诊断价值,为胃癌骨转移的早期诊断提供依据。方法收集522例胃癌患者的临床资料及血清标志物(ALP、CEA、CA19-9)检测结果,根据有无骨转移将入组患者分为骨转移组(n=91)和无骨转移组(n=431)。参照Soloway分级标准将骨转移分为3级,进一步分析ALP、CEA、CA19-9三者单独与联合检测在胃癌骨转移中的诊断价值及其与骨转移分级之间的关系。结果骨转移组患者ALP、CEA、CA19-9水平均明显高于无骨转移组,差异均有统计学意义(P﹤0.01)。ALP、CEA、CA19-9均是胃癌发生骨转移的影响因素(P﹤0.05)。3种血清标志物联合检测的曲线下面积(AUC)大于任何指标单独检测,但ALP单独检测与三者联合检测的AUC值差异不明显;3种血清标志物联合检测诊断效能优于单独检测。ALP与CA19-9水平随着骨转移分级升高呈上升趋势。经Spearman相关分析显示,ALP、CA19-9与骨转移分级均呈正相关(r=0.436、0.391,P﹤0.05),且ALP在评价胃癌骨转移严重程度方面优于CA19-9。结论ALP、CEA、CA19-9联合检测对胃癌骨转移的诊断价值优于单项检测,为胃癌骨转移的早期诊断以及监测提供参考。但考虑到患者的经济因素,对于临床上怀疑胃癌骨转移的患者,ALP是首选的检测指标,且该指标可作为评价胃癌骨转移严重程度的生物学标志物。     

Carcinoembryonic antigen, alpha-fetoprotein and hepatoma alkaline phosphatase in gastric carcinoma

Reported here is a 38-year-old woman who had a gastric cancer accompanied with liver metastasis. Abnormal serum levels of a carcinoembryonic antigen, alpha-fetoprotein, and an alkaline phosphatase isozyme were observed persistently after a gastrectomy. The properties of this alkaline phosphatase isoenzyme were identical to a hepatoma alkaline phosphatase type. Histologic findings of the stomach revealed a poorly differentiated adenocarcinoma. The patient died on the 180th postoperative day.     

碱性磷酸酶同工酶在原发性肺癌骨转移诊断中的应用

目的:探讨骨碱性磷酸酶同工酶（bone alkaline phosphatase,BALP）与原发性肺癌骨转移的相关性。方法:采用神经氨酸苷酶处理血清,琼脂糖电泳法分析测定50名健康体检者和131例原发性肺癌患者血清中的血清碱性磷酸酶（ALP）同工酶。结果:原发性肺癌组的总ALP和同工酶均高于正常对照组,原发性肺癌骨转移组的总ALP和BALP活性均显著高于对照组和无骨转移组,原发性肺癌无骨转移组的总ALP和BALP活性和对照组无显著性差异。结论:骨型ALP与原发性肺癌骨转移有一定的相关性,经神经氨酸苷酶处理血清后,采用琼脂糖电泳法分离ALP同工酶有助于临床辅助诊断原发性肺癌有无骨转移。     

Plasma acid and alkaline phosphatase in patients with breast cancer

Acid and alkaline phosphatase were determined in 107 breast cancer patients to study their potential value in case of bone metastases. The patients were divided into 4 groups: A, patients without metastases (n = 34); B, metastatic patients without bone lesions (n = 37); C, patients with metastases in and outside of bones (n = 24), D, patients with bone-only metastases (n = 12). Tartrate resistant acid phosphatase (TR-ACP), and bone alkaline phosphatase (bone-ALP) were significantly higher in patients with metastases than in patients without. However, no difference in TR-ACP was observed between subgroups of metastatic patients.     

The prognostic value of pretreatment CA 125 in patients with advanced ovarian carcinoma

BACKGROUND:

The objective of the current study was to determine the prognostic significance of a pretreatment serum CA 125 level in patients with advanced epithelial ovarian carcinoma (EOC) who received treatment with a standard chemotherapy regimen.

METHODS:

Patients with International Federation of Gynecology and Obstetrics stage III/IV ovarian carcinoma who were on 1 of 7 Gynecologic Oncology Group (GOG) phase 3 trials and received treatment with a standard regimen of intravenous cisplatin and paclitaxel were included. A Cox regression model was used to assess the impact of CA 125 levels drawn before the initiation of chemotherapy on progression‐free survival (PFS) both overall and by subgroup, including surgical debulking status, disease stage, and histologic subtype.

RESULTS:

In total, 1299 patients who were on the cisplatin/paclitaxel arms of the GOG trials were eligible. The median CA 125 level was 246 U/mL. Only 7.6% of patients had a normal CA 125 level (≤35 U/mL). The lowest median CA 125 level was observed in the group with mucinous tumors; however, 69% of women who had mucinous tumors had abnormal CA 125 levels. Shorter PFS was observed with increasing CA 125 and persisted in multivariate analysis. Overall and in the serous subgroup, a 1‐fold increase in CA 125 level was associated with a 7% increase in the hazard of disease progression (P < .001). This association was even more pronounced in patients who had stage III disease that was debulked to microscopic disease (15%; P = .003) and in patients who had endometrioid tumors (17%; P = .001).

CONCLUSIONS:

A normal CA 125 level in the setting of advanced EOC was rare even after surgical debulking. The pretreatment CA 125 level was an independent predictor of PFS in patients with advanced EOC who received a standard chemotherapy regimen, particularly in the setting of disease that was debulked to a microscopic residual and in the serous or endometrioid subtypes. Cancer 2009. © 2009 American Cancer Society.     

全身骨显像联合血清骨型碱性磷酸酶诊断肺癌骨转移

 【摘要】　目的　探讨全身骨显像和血清骨型碱性磷酸酶（B-ALP）对肺癌骨转移的诊断价值。方法　对58例肺癌患者进行全身骨显像,同时测定血清碱性磷酸酶（ALP）、B-ALP 水平,对其结果进行比较分析。结果　58例患者中,骨转移33例,转移率56.90 %。其中肺腺癌的骨转移率为70.97 %（22／33）,肺鳞状细胞癌为42.86 %（9／21）,差异有统计学意义（χ2＝4.109,P＝0.0427）。血清B-ALP水平≥150 U／L者骨转移发生率为95.46 %（21／22）,血清B-ALP水平＜150 U／L者骨转移发生率为33.33 %（12／36）,差异有统计学意义（χ2＝21.487,P＝0.0000）。骨转移灶≤3处组与＞3处组B-ALP分别为（125.00±25.00）U／L和（176.14±49.09）U／L,两组间B-ALP水平差异有统计学意义（精确概率法,P＝0.0013）。在诊断敏感性和特异性的比较中,骨显像诊断的敏感度最高,达到93.94 %,但其特异度最低,为92.00 %;而骨显像+ B-ALP敏感度降低至57.58 %,但特异度可达到100.00 %。结论　诊断肺癌骨转移应首选骨显像。同时检测血清B-ALP有助于明确肺癌患者核素骨显像异常表现的病变性质,联合检测B-ALP+骨显像可以提高诊断特异度。血清B-ALP对肺癌骨转移诊断及病情判断有一定临床应用价值。     

Diagnostic value of high molecular weight alkaline phosphatase in detection of hepatic metastasis in patients with lung cancer

High molecular weight alkaline phosphatase (HMW-ALP) was measured in the sera of 126 patients with lung cancer to determine its diagnostic value in the detection of hepatic metastasis. This isoenzyme was found in 21 of 24 patients with hepatic metastasis and in 27 of 102 patients without hepatic metastasis. When 10 U/L was used as a cut-off value, the sensitivity, specificity, and accuracy of this test were 71%, 89%, and 86%, respectively. From the standpoint of histologic type, this test was most useful in patients with small cell carcinoma. HMW-ALP was not detected in the sera of 15 controls. It is concluded that HMW-ALP is a useful marker for hepatic metastasis in patients with lung cancer.