Serum alkaline phosphatase and gamma-glutamyltranspeptidase in metastatic malignant tumors

Levels of gamma-glutamyltranspeptidase and total, alpha 2 and alpha 1-alkaline phosphatase versus dissemination pattern and survival time were studied in patients with stage III and IV tumors of various sites. No significant changes in the activity of the said enzymes were registered in cases of single hepatic metastasis and metastasis-free liver. A slight increase in the enzymes' activity was observed in patients with pronounced liver involvement within months 10-4 before death. That was followed by a sharp and marked (3-4 times normal) rise in the levels during months 4-3. Changes in enzyme activity within the terminal 12 months were described with the aid of polynoms on the basis of regression analysis. A correlation between liver mass and degree of rise in serum enzymes levels was established.     

Placental alkaline phosphatase, alphafetoprotein and carcinoembryonic antigen in testicular tumors. Tissue typing by means of cytologic smears.

Indirect immunofluorescence and radioimmunoassay with specific rabbit antisera demonstrated the occurrence of alphafetoprotein (AFP), carcinoembryonic antigen (CEA) and placental alkaline phosphatase (PLAP) in primary testicular tumor cells. Embryonal carcinomas had AFP- and CEA-containing cells, sometimes PLAP. PLAP and sometimes CEA were found in seminoma cells. Sera from patients with advanced non-seminomatous tumors could contain any of these antigens or any combination of them. Sera from patients with seminomas had raised PLAP or CEA. PLAP appears to be a new marker for seminoma.     

C-myc蛋白在睾丸肿瘤中的表达及意义

目的　探讨C myc基因蛋白与睾丸肿瘤生物学行为及预后的关系。方法　采用免疫组化S P法对 38例睾丸肿瘤和 10例正常睾丸组织中C myc蛋白表达进行了定量分析。结果　 31例 (81.6 % )睾丸肿瘤显示阳性反应 ,正常睾丸组织为阴性反应。肿瘤组和正常组组织阳性细胞率分别为 2 4 .99%和 3.2 6 % ,两者相比有非常显著性差异 (P <0 .0 1)。在睾丸肿瘤中C myc蛋白的表达程度与肿瘤病理分级、临床分期无关 (P >0 .0 5 )。C myc表达在精原细胞瘤组及非精原细胞瘤组间无显著性差异 (P >0 .0 5 )。结论　C myc蛋白的异常表达可能在睾丸肿瘤的发生、发展过程中起着促进作用。     

Monoclonal antibody assay of serum placental alkaline phosphatase in the monitoring of testicular tumours

A monoclonal antibody (H17E2) recognising both placental alkaline phosphatase (PLAP) and testicular PLAP-like alkaline phosphatase was incorporated in a solid phase immunoassay. This was used to measure levels of PLAP in 257 sera from 148 patients with germ cell neoplasms of the testis. High levels of PLAP were found in all patients with active seminomas (mean 0.85 O.D.) compared to those in clinical remission (mean 0.20 O.D.) (P less than 0.0001). More importantly, changing levels of PLAP correlated with the course of disease in 79 samples from 33 patients with seminoma (P less than 0.0001). Elevated PLAP levels were also noted in patients in remission who were smokers (mean 0.32 O.D.) compared to non-smokers (mean 0.15 O.D.) (P less than 0.001). These data demonstrate that determination of PLAP levels using this sensitive immunoassay is an important new adjunct in the monitoring of the response to treatment in patients with seminoma.     

Occurrence of heat-labile Regan type of alkaline phosphatase in hematopoietic tumors.

The physiocochemical and immunological properties of alkaline phosphatase extracted from Hodgkin's nodes, non-Hodgkin's lymphoma nodes and leukemic leukocytes have been studied. The alkaline phosphatase from these three tumor types possesses the same biophysical and biochemical properties and immunological determinants as the placental alkaline phosphatase. However, it is more heat-labile than the placental isoenzyme. Immunological experiments indicate that, of these tumor types, Hodgkin's tumor contains the largest amounts of heat-labile Regan type of alkaline phosphatase.     

Frequent PD-L1 expression in testicular germ cell tumors

Background:

Many testicular germ cell cancers are curable despite metastatic disease, but about 10–15% of patients fail cisplatin-based first-line treatment. Immunotherapy is considered as additional treatment approach for these patients. Inhibition of the interaction between Programmed Death Receptor 1 (PD-1) and Programmed Death Receptor Ligand 1 (PD-L1) enhances T-cell responses in vitro and mediates clinical antitumour activity. We analysed the expression of PD-L1 in testicular germ cell tumours to evaluate its potential as target for immunotherapeutic strategies.

Methods:

Immunohistochemistry was performed in 479 formalin-fixed paraffin-embedded specimens using a rabbit monoclonal antibody (E1L3N). The tissue microarray consisted of 208 pure seminomas, 121 non-seminomas, 20 intratubular germ cell neoplasia unclassified (IGCNU) and 20 specimens of non-neoplastic testicular tissue.

Results:

Programmed Death Receptor Ligand-1 expression was found in 73% of all seminomas and in 64% of all non-seminomas. None of 20 IGCNU and none of 20 normal tissue specimens exhibited PD-L1 expression. PD-L1 positive stromal cells were only detected in seminomas, but not in non-seminomas. The anti PD-L1 antibody showed a pre-dominantly membranous staining pattern in testicular tumour cells, as well as expression in stromal cells.

Conclusions:

This frequent expression of PD-L1 in human testicular germ cell tumours suggests that patients with testicular germ cell tumours could profit from immunotherapeutic strategies using anti-PD1 and anti-PDL1 antibodies.     

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。     

Identification of testicular atypical germ cells by an immunohistochemical technique for placental alkaline phosphatase

The identification of atypical testicular germ cells is often difficult by by routine histologic examination. By immunohistochemical detection of placental alkaline phosphatase (PLAP) and by periodic acid Schiff staining of glycogen, atypical germ cells were easily identified in testicular samples. Forty-one fetal and adult testes were used for a preliminary study, and 121 testes from infants and adults with either cryptorchidism or germ cell tumors were studied for the presence of atypical germ cells. Two types of clear germ cells were differentiated histochemically, and one with PLAP-positive cell surfaces and glycogen-rich cytoplasm was considered to be atypical. The alkaline phosphatase of atypical germ cells appeared to be similar to that found in a few germ cells of early fetal testes. The atypical germ cells seemed to be multi-potential malignant cells capable of developing not only into seminoma but also into other germ cell tumors. Only in yolk sac tumor of infants were the atypical germ cells absent from tumor-adjacent seminiferous tubules.     

The pattern of gamma-glutamyl transpeptidase,alkaline phosphatase,serum glutamyl oxalate transaminase and serum glutamyl pyruvate transaminase in patients with disseminated non-seminomatous testicular tumors

The serum enzyme activities of gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), serum glutamyl oxalate transaminase (sGOT) and serum glutamyl pyruvate transaminase (sGPT) were determined longitudinally in 51 patients with a disseminated non-seminomatous testicular tumor. Elevated levels of one or more enzymes before chemotherapy were observed in 13 patients, all with stage III disease. If, after two cycles of chemotherapy, the established tumor markers alpha-fetoprotein (AFP), human chorionic-gonadotropin (HCG) and/or lactate dehydrogenase (LDH) were normalized, the initially increased enzyme activities were declined to normal values as well. Peaking concentrations of one or more of the tumor markers during induction chemotherapy, probably due to tumor cell lysis, were found in 34 of 45 marker-positive patients (76%). In addition, increases of one or more of the investigated enzyme activities were also noticed in 20 patients. In 76% of these patients the highest point of the tumor marker concentration coincided well with that of the enzyme activities. Indications are given that the peak activities were probably not caused by liver damage. Enzyme elevations were also found in 3 out of 7 patients with progressive disease. The behaviour of the enzyme activities of GGT, AP, sGOT and sGPT in patients with a disseminated non-seminomatous testicular tumor coincided with the known tumor markers. It favors the hypothesis that these enzymes are synthesized in the tumor. The mortality amongst stage III patients with or without initially raised GGT levels differed significantly (P < 0.02). Finally, it is concluded that in patients with a non-seminomatous testicular tumor, sGOT, sGPT, GGT and AP cannot be used to diagnose liver function.     

Acid and alkaline phosphatase activities in homogenates and subcellular fractions of human brain tumors

This study is a quantitative analysis of acid and alkaline phosphatase activity in human brain tumor homogenates and subcellular fractions, in parallel with normal brain tissue. Glioblastoma multiforme, meningioma, astrocytoma and normal tissue samples were separated by ultracentrifugation into five subcellular fractions: nuclei (N), mitochondria (M), microsomes (P), ribosomes (R) and supernatant (S). These two phosphatases showed significant increase in astrocytoma and meningioma tissue homogenates, compared with normal brain tissue. Alkaline phosphatase levels were determined to increase significantly in glioblastoma multiforme tissue homogenates as compared with normals, while those of acid phosphatase were observed to decrease. The results of this investigation also indicate that the subcellular distributions of acid and alkaline phosphatase show differences in the different tumor types. This observation is evidence against metabolic uniformity in tumoral tissue.     

p53 expression and tumor proliferative activity in testicular germ-cell tumors

We evaluated p53 expression and tumor proliferative activity (TPA) using monoclonal antibodies to Ki-67 and proliferating cell nuclear antigen (PCNA) in 26 patients with seminomatous and nonseminomatous testicular germ-cell tumors (GCTs). Correlation between p53 expression and TPA, as well as the clinical correlation with the expression of these proteins were also assessed. There were eight cases of pure seminoma and 18 cases of nonseminomatous GCTs, collectively consisting of 45 tumors or tumor components. The nonseminomatous GCTs were mixed or pure and included choriocarcinoma (CC), embryonal carcinoma (EC), immature teratoma (IMT), mature teratoma (MT), seminoma, and yolk sac tumor (YST). The ages of the patients with seminomatous GCTs ranged from 24 to 47 years (mean, 34 years) and those for patients with nonseminomatous GCTs ranged from 17 to 43 years (mean, 29 years). Sixteen (44%) of the 36 nonseminomatous GCTs or tumor components were positive for p53 protein. Ten (91%) of eleven ECs, three (38%) of eight YSTs, two (20%) of ten MTs, and the single case of CC were positive for p53 protein. All nine seminomas and three of six IMTs were only focally positive for p53 protein. The p53 expression in ECs and YSTs was significantly higher than that in IMTs, MTs, and seminomas (P=0.0001). TPA was present in the majority of the seminomatous and nonseminomatous GCTs, and was significantly higher in ECs and YSTs than in seminomas, MTs, and IMTs (Ki-67, P=0.0001; PCNA, P=0.0006). In the majority of the cases PCNA expression was higher than Ki-67 expression (P=0.0001). The mean TPA percentage was significantly higher in the p53-positive tumors or tumor components (EC and YST) when compared with the mean TPA percentage in those neoplasms that were focally positive or negative for p53 protein (Ki-67, P=0.003; PCNA, P=0.046). p53 expression was also associated with histologically aggressive tumors (ECs and YSTs) that also exhibit high TPA. No relationship appears to exist between the three tumor markers and the clinical stage or the patients' follow-up and outcome in this small series. Further studies are necessary to elucidate the roles of p53 and proliferation markers in testicular tumorigenesis and as prognostic markers.     

Clinical relevance of HER-2/neu expression in germ-cell testicular tumors

BACKGROUND: Amplification and/or overexpression of HER-2/neu are associated with poor clinical outcome in several epithelial tumors. However, the exact prognostic role of HER-2/neu expression in testicular germ-cell tumors is equivocal. PATIENTS AND METHODS: Since teratomas are relatively chemoresistant tumors, we evaluated the HER-2/neu alterations of 59 primary testicular teratomas and mixed germ-cell tumors containing teratomatous components using the standardized immunohistochemical method (IHC) (HercepTest) and Fluorescence in Situ Hybridization (FISH). RESULTS: HER-2/neu overexpression was detected in 14 (24%) out of 59 specimens. With IHC, teratomatous and choriocarcinoma components showed significantly higher HER-2/neu expression compared to other histological subtypes of GCTs (p=0.0095). A statistically significant correlation (p=0.0004) can be established between HER-2/neu status and clinical stage of the disease. Similarly, a significant correlation was observed between HER-2/neu overexpression and clinical outcome (p=0.0077). None of the specimens had definite HER-2/neu gene amplification. CONCLUSION: Our results suggest that HER-2/neu overexpression is associated with an adverse clinical outcome and has a prognostic role in testicular germ-cell tumors. Further studies are needed to evaluate the exact background of HER-2/neu overexpression in germ-cell tumors and the role of anti-HER-2/neu antibodies in the treatment regimens for this malignancy.