Serum Lactate Dehydrogenase Isoenzyme 1 Research Articles

Serum lactate dehydrogenase isoenzyme 1 as predictor of tumor-associated death in patients with testicular germ cell tumours.

Serum lactate dehydrogenase iso-enzyme 1 (S-LD-1) was determined in 24 patients with testicular germ cell tumours who died during follow-up. Serum samples were obtained at the start of chemotherapy or late into the clinical course for those without evidence of a tumour. Seven of the eight patients with tumour-associated death had S-LD-1 > 150 U l-1 (median 260 U l-1 range 90-905 U l-1, as did two of the six who died without evidence of a tumour (median 134 U l-1 range 89-128 U l-1) (P = 0.03, Mann-Whitney U-test, two-tailed). The remaining 10 patients had previously been reported as to prediction of S-LD-1 for the prognosis, and were evaluated only as to the reproducibility of the S-LD-1 determination. S-LD-1 was determined in two serum samples obtained concomitantly from eight of these 10 patients: the difference between the two S-LD-1 determinations was median 6% of the average of the two S-LD-1 determinations (25-75% range 3-17%). Our study showed an unforeseeable high level of imprecision of the assay system. Nevertheless, S-LD-1 determinations in the regular monitoring of patients with testicular germ cell tumours may be useful for predicting tumour-associated deaths.

Testicular cancer.

The purpose of this article is to review the recent clinically relevant literature on testicular cancer. Recent studies suggest that an increased incidence of testicular cancer is due to a birth-cohort effect and secondary to early exposure. Work on identifying tumor prognostic characteristics suggests that proliferation and apoptosis markers as well as serum lactate dehydrogenase isoenzyme 1 (S-LD-1) may have value. Poor-risk patients may benefit from intensive treatment despite a possible increased risk of significant toxicity and treatment related deaths. Studies continue to show the efficacy of radiation for stage I and stage II seminoma, but another study adds to the evidence that adjuvant carboplatin may be an acceptable alternative in stage I disease. Surgical studies suggest that even patients with minimal findings on computed tomography after chemotherapy are at risk for harboring vital tumor. Surveillance is shown to be an acceptable choice for highly compliant patients with early stage disease. Risk factors predictive of bleomycin pulmonary toxicity are proposed. Fertility remains an area of concern. Testicular cancer research continues to modify current therapies, increase the understanding of the molecular basis of the disease, and improve the risk stratification of the patient population so as to minimize exposure to treatment-related morbidity and toxicity.

Serum lactate dehydrogenase isoenzyme 1 and prediction of death in patients with metastatic testicular germ cell tumors.

The International Germ Cell Cancer Collaborative Group study of patients with metastatic testicular germ cell tumors showed that catalytic concentration of serum lactate dehydrogenase (S-LD), serum alpha-fetoprotein concentration (S-AFP), and serum human chorionic gonadotropin concentration (S-hCG) predicted death from tumor. The recent international TNM classification (T primary tumor, N lymph node metastasis, M distant metastasis) is based on these results. The aim of our study was to evaluate whether catalytic concentration of S-LD isoenzyme 1 (S-LD-1) was a better predictor than the criteria used for the international classification. In an evaluation series of 44 patients from Odense University Hospital, Denmark, a raised S-LD-1 (>1.0 x upper limit of reference values) had a predictive value for death from tumor in 5-years observation of 46%. The predictive value was 46% for S-LD, 25% for S-AFP, and 40% for S-hCG. A normal SLD-1 had a predictive value for survival over 5-years observation of 100%. It was 81% for S-LD, 75% for SAFP, and 77% for S-hCG. The fraction of the patients who died of tumor and had a raised tumor marker value was 100% for S-LD-1, 46% for S-LD, 9% for S-AFP, and 18% for S-hCG. The fraction of patients with a normal serum tumor marker value among those who survived was 61% for S-LD-1, 81% for S-LD, 94% for SAFP, and 94% for S-hCG. A validation series of 37 patients treated at the University of Texas MD Anderson Cancer Center showed similar findings. Combining the patients in the two series, a raised value of SLD-1 classified more patients into a subgroup with an impaired survival (53%) than S-LD (35%), S-AFP (6%), or S-hCG (11%), and the high risk subgroups based on the international classification (40%). The findings have implications for the staging and treatment of patients with metastatic testicular germ cell tumors.

Analytical quality specifications for serum lactate dehydrogenase isoenzyme 1 based on clinical goals.

The aim of the study was to deduce analytical quality specifications for the determination of catalytic concentration of serum lactate dehydrogenase isoenzyme 1 (S-LD-1) according to clinical goals (the clinical utility model). We defined clinical goals for false positive and false negative S-LD-1 measurements in the monitoring of patients with testicular germ cell tumors (TGCT), clinical stage I, on a surveillance only program. The absolute S-LD-1 catalytic concentrations were routinely corrected for contamination from preanalytical hemolysis. A reference group of 37 men had a near In-Gaussian distribution for the absolute S-LD-1 catalytic concentration. The geometric mean was 76 U/l and an S-LD-1 >128 U/l (99.72 percentile, the decision limit) indicated a high risk of a relapse of TGCT. We have previously shown that an S-LD-1 >160 U/l (treatment limit) was associated with a suboptimal outcome from the treatment of metastatic TGCT. The maximum allowable analytical positive bias was 5 U/l, and the maximum allowable analytical negative bias was -32 U/l. The maximum allowable analytical coefficient of variation, CV(A), was 11% (approximately 14 U/l) at a bias = -5 U/l. For S-LD-1 measurements not corrected for hemolysis, the decision limit was 145 U/l, the maximum allowable negative bias -19 U/l, and CV(A) 8%(approximately 12 U/l). A routine correction for hemolysis had a large impact on the analytical quality specifications.

Serum lactate dehydrogenase isoenzyme 1. An early indicator of relapse in patients with testicular germ cell tumors.

The present study aimed to evaluate serum lactate dehydrogenase isoenzyme 1 (S-LD-1) as an indicator of relapse for patients with testicular germ cell tumors. Twenty-seven patients were investigated with repeated determinations of S-LD-1 from diagnosis to relapse; 9 had seminoma and 18 nonseminomatous tumors. Eleven of 21 had raised S-LD-1 at relapse (4 with seminoma). Seven of the 27 patients had a raised S-LD-1 for median 2 months (1.4-4.5 months) before relapse was detected. Thus, S-LD-1 is of use, complementary to clinical examinations, determinations of serum alpha fetoprotein and human chorionic gonadotropin, and CT scans, in monitoring patients with testicular germ cell tumors for relapse.

Analytical bias by contamination from hemolysis in determination of serum lactate dehydrogenase isoenzyme 1 in patients with testis germ cell tumors.

We investigated the impact of correction for contamination from hemolysis on serum lactate dehydrogenase isoenzyme 1 (S-LD-1) determinations. A study of hemolysates from 7 control patients showed a mean correction factor for the contamination of 0.1 U/L S-LD-1 for each 1 mg/L serum hemoglobin (S-Hb). S-LD-1 in a series of blood samples from 44 patients (EJC 1992;28:410-5) would decrease median 24 U/L (range 8-70 U/L) if the measurements were corrected with this factor. So we advice to correct S-LD-1 determinations for the contamination with a common correction based on the S-Hb concentrations in the samples.

Specific Assay of Serum Lactate Dehydrogenase Isoenzyme 1 by Proteolysis with Alpha-Chymotrypsin and Protein Denaturation

We devised a method for assaying serum lactate dehydrogenase isoenzyme 1 (LD-1) activity specifically by preincubation with alpha-chymotrypsin and guanidine. Cleavage of phenylalanine bonds in the loop of A and B subunits of LD-3, LD-4, and LD-5 isoenzymes (residues 117-119) by incubation with alpha-chymotrypsin for a short time completely inactivated these isoenzymes and partially inactivated LD-2. Addition of guanidine (0.50 mol/L, pH 7.8) to the incubation mixture containing the chymotrypsin completed the inactivation of LD-2. As much as 4000 U/L of LD-2, LD-3, LD-4, and LD-5 were inactivated, whereas LD-1 was affected only slightly. Results by this method (y) correlated well with those by the Roche Isomune immunochemical LD-1 method (x): y = 0.98 x -0.11, r = 0.99 (n = 60). Within-run CVs were 0.5-2.5%. Several common interferents had no effect. In 500 healthy people, serum LD-1 ranged between 66 and 130 U/L, with a mean +/- SD of 88 +/- 15 U/L.

Serum lactate dehydrogenase isoenzyme 1 activity in patients with testicular germ cell tumors correlates with the total number of copies of the short arm of chromosome 12 in the tumor.

The aim of our study was to assess the relationship between the serum lactate dehydrogenase isoenzyme 1 (S-LDH-1) activity in patients with testicular germ cell tumors and the number of copies of the short arm of chromosome 12 (12p) present in tumor. Twenty-seven adult patients with measurable tumor lesions were studied. Twenty-five had three or more copies of chromosome 12 per cell in the tumors. Nineteen had one or more copies of a specific chromosomal abnormality, an isochromosome of the short arm of chromosome 12, i(12p). Fourteen had increased S-LDH-1 levels. S-LDH-1 activity correlated significantly with the product of total tumor volume and the total number of copies of the short arm of chromosome 12 present per cell (total tumor 12p). We conclude that the total number of copies of the short arm of chromosome 12 in the tumors is most probably a factor contributing to the LDH-1 activity released from the tumors.

Lactate dehydrogenase isoenzyme-1 in serum for detection of peri-operative myocardial infarction after cardiac surgery.

We prospectively studied changes in serum lactate dehydrogenase isoenzyme-1 (LD-1, EC 1.1.1.27) in 99 consecutive patients after either coronary artery bypass grafting (CABG, n = 61), isolated cardiac-valve replacement (n = 24), or the two procedures combined (n = 14); 86 of these had no clinical evidence of peri-operative myocardial infarction (MI). Blood was sampled immediately after surgery and at 6-h intervals for up to 42 h thereafter. LD-1 was isolated by using the LD M-subunit antiserum. Samples from the non-MI patients were used to establish the reference intervals for LD-1. By 24 h after surgery, mean serum LD-1 values were higher (P less than 0.001) in non-MI patients who underwent isolated valve replacement (222 +/- 74 U/L) or combined CABG and valve replacement (266 +/- 58 U/L) than in 50 non-MI patients who underwent CABG alone (134 +/- 42 U/L). Separate reference intervals were determined for CABG and other patients at each sampling time. By 24 h after operation, LD-1 exceeded these reference intervals in the 10 CABG and two combined-procedure patients in whom other evidence of MI was present. Measurement of LD-1 24 to 42 h after cardiac surgery appears to be a useful test for the diagnosis of perioperative MI.

Serum lactate dehydrogenase isoenzyme-1 in children with yolk sac tumor.

Although in recent years the evidence of an increase in serum lactate dehydrogenase isoenzyme-1 (LDH-1) in patients with germ cell tumor (GCT) has attracted attention, there have only been a few reports concerning yolk sac tumor (YST), which is a frequent type of GCT in childhood. Serum LDH isoenzymes were determined in eight children with YST, and an increase in LDH-1 was found in seven of them, excluding one in an early stage. On the basis of the findings of serial serum LDH-1 levels during treatment and of LDH isoenzyme pattern in tumor tissues, it is presumed that the increased serum LDH-1 is derived from tumor tissues. LDH-1 seems to be useful as a tumor marker, not specific for YST but associated with the whole spectrum of GCT, for monitoring of YST.