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In a CODE-MI sub-study, six troponin assays were evaluated over 12 months using 3-samples (normal, female and male 99th-percentile levels; n=2,142 results from 67 instruments). Mean differences varied per assay with maximum values being ±4, ±8 and ±9 ng/L at the normal and sex-specific 99th-percentiles, respectively. A pragmatic approach, combining all assays, established maximum differences of ±3 ng/L or ±30%.

It is timely with interest in prostate cancer screening rekindled by the recently revised and updated recommendations issued by the United States Preventative Services Task Force (USPSTF)3 (1) that this cancer-themed issue of the Journal of Applied Laboratory Medicine includes the study by Higgins and coauthors (2), who evaluated the analytical performance of one such screening test designed to avoid the overdiagnosis of indolent prostate cancer, the 4Kscore. Such information is also timely, if not overdue, given that this test has been in use since 2014 with only a single published Abstract (3), presented at the 2015 AACC Annual Meeting, describing the test's analytical performance and …

To the Editor: International societies and expert groups recommend using sex-specific upper reference limits (URLs)1 for interpretation of high-sensitivity cardiac troponin (hs-cTnI/T) assays (1, 2). Despite advances in our understanding of cTn in adults, the effect of age and sex on cTn in pediatric populations is less understood. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) previously determined 97.5th and 99th percentiles for the Abbott hs-cTnI assay in a healthy pediatric cohort (3). These data represented the first attempt to characterize hs-cTnI in healthy children but did not include neonates nor were sex-specific differences evident. It is unclear, however, what cTnT URLs would be in this population because cTnT is a different protein and there are differences in analytical sensitivity and specificity between hs-cTnT and hs-cTnI assays (1–4). Establishing pediatric reference values for cTn is important because its measurement has several clinical indications in pediatrics, including monitoring children with postoperative myocarditis and congenital pediatric heart disease. Serum samples from 598 children and adolescents were selected from the CALIPER biobank. Samples from participants

Background: Updated National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed.Methods: Published reports relevant to use of tumor markers for 5 cancer sites—testicular, prostate, colorectal, breast, and ovarian—were critically reviewed.Results: For testicular cancer, α-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are recommended for diagnosis/case finding, staging, prognosis determination, recurrence detection, and therapy monitoring. α-Fetoprotein is also recommended for differential diagnosis of nonseminomatous and seminomatous germ cell tumors. Prostate-specific antigen (PSA) is not recommended for prostate cancer screening, but may be used for detecting disease recurrence and monitoring therapy. Free PSA measurement data are useful for distinguishing malignant from benign prostatic disease when total PSA is Conclusions: Implementation of these recommendations should encourage optimal use of tumor markers.

Background: This report presents updated National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines summarizing quality requirements for the use of tumor markers. Methods: One subcommittee developed guidelines for analytical quality relevant to serum and tissue-based tumor markers in current clinical practice. Two other subcommittees formulated recommendations particularly relevant to the developing technologies of microarrays and mass spectrometry. Results: Prerequisites for optimal use of tumor markers in routine practice include formulation of the correct clinical questions to ensure selection of the appropriate test, adherence to good clinical and laboratory practices (e.g., minimization of the risk of incorrect patient and/or specimen identification, tube type, or timing), use of internationally standardized and well-characterized methods, careful adherence to manufacturer instructions, and proactive and timely reactions to information derived from both internal QC and proficiency-testing specimens. Highly desirable procedures include those designed to minimize the risk of the reporting of erroneous results attributable to interferences such as heterophilic antibodies or hook effects, to facilitate the provision of informative clinical reports (e.g., cumulative and/or graphical reports, appropriately derived reference intervals, and interpretative comments), and when possible to integrate these reports with other patient information through electronic health records. Also mandatory is extensive validation encompassing all stages of analysis before introduction of new technologies such as microarrays and mass spectrometry. Provision of high-quality tumor marker services is facilitated by dialogue involving researchers, diagnostic companies, clinical and laboratory users, and regulatory agencies. Conclusions: Implementation of these recommendations, adapted to local practice, should encourage optimization of the clinical use of tumor markers.

Human kallikrein 6 protein is a newly discovered human kallikrein. We determined the amount of human kallikrein 6 in extracts of 182 ovarian tumours and correlated specific activity (ng hK6 mg−1 total protein) with clinicopathological variables documented at the time of surgical excision and with outcome (progression free survival, overall survival) monitored over a median interval of 62 months. Thirty per cent of the tumours were positive for human kallikrein 6 (>35 ng hK6 mg−1 total protein). Human kallikrein 6-specific immunohistochemical staining of four ovarian tissues that included benign, borderline and malignant lesions indicated a cytoplasmic location of human kallikrein 6 in tumour cells of epithelial origin, although the intensity of staining was variable. Tumour human kallikrein 6 (ng hK6 mg−1 total protein) was higher in late stage disease, serous histotype, residual tumour >1 cm and suboptimal debulking (>1 cm) (P

Prenatal screening for chromosomal aneuploidies is a fundamental part of routine obstetric care in most countries. Typically, maternal age, weight, ethnicity, serum biomarkers (including pregnancy-associated plasma protein A, human chorionic gonadotropin, α-fetoprotein, inhibin A, and estriol), and sonographic features (i.e., nuchal translucency) are included in a risk algorithm to determine the probability of the fetus being affected. Pregnant women identified as at high risk according to the prenatal screen can then undergo invasive procedures, such as amniocentesis and chorionic villus sampling, to confirm the diagnosis. Current prenatal-screening methods are able to identify approximately 90% of pregnancies affected by trisomy 21 (Down syndrome) at a false-positive rate of approximately 5%. Given that the prevalence of chromosomal aneuploidies is generally quite low, a false-positive rate of 5% means that a large number of women with unaffected pregnancies undergo invasive procedures, putting the fetus at an unnecessary risk for miscarriage. The discovery of fetal cell-free DNA in the plasma of pregnant women 14 years ago opened up the possibility of identifying chromosomal abnormalities noninvasively, through a single blood sample. Approximately 10% of cell-free DNA in the maternal circulation is of fetal origin, and this property was initially exploited to determine rhesus D status and the sex of the unborn fetus. The advent of next-generation DNA sequencing, however, has allowed prenatal detection of chromosomal aneuploidies, including trisomy 21, from maternal blood. In brief, the proportion of chromosome 21 DNA molecules in maternal plasma is measured directly; an increase above a predetermined threshold is indicative of trisomy 21. The clinical performance of this noninvasive prenatal test has been promising, with recent clinical studies having shown a diagnostic sensitivity of 100% and a diagnostic specificity of 98%–99%, compared with full karyotyping by invasive means. When used as a second-tier screening procedure, this technology also has the …

We report the measure of prostate-specific antigen (PSA) from extracts of blood dried on filter paper. Five 3-mm (diameter) paper discs containing approximately 25 microL of dried whole blood were punched from the filter paper and extracted with 500 microL of buffer. Recovery of PSA was > 92%. Imprecision of the filter paper procedure was 0.35 micrograms/L. PSA recovery was unaffected whether blood was applied to the filter as one 85-microL aliquots, two 43-microL aliquots, or three 28-microL aliquots. PSA is contained in the plasma fraction. Variation in hematocrit from 0.61 to 0.31 caused 1 month at -20 to 37 degrees C and showed no loss of recovery after being mailed to a hot climate. We conclude that the filter paper procedure can reliably distinguish normal from increased concentrations of PSA and that it could facilitate screening to detect occult prostate cancer in large-scale mail-in programs to centralized laboratories.

The National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for Use of Tumor Markers are intended to encourage more appropriate use of tumor marker tests by primary care physicians, hospital physicians and surgeons, specialist oncologists, and other health professionals. This introduction accompanies the e-publication of 2 reports summarizing NACB Quality Requirements for use of tumor markers in clinical practice (1) and NACB Guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers (2). Two further reports will follow, summarizing the NACB Guidelines for use of tumor markers in liver, pancreatic, gastric, bladder, and cervical cancers and the NACB Guidelines for use of tumor markers in parathyroid, thyroid, neuroendocrine and lung cancers, monoclonal gammopathies, and melanoma. Here we report the updating and extension of practice guidelines first proposed in 2002 (3). Undertaken under the direction of a steering committee appointed by the NACB (Table 1⇓ ), this process involved consideration of 16 specific cancer sites, together with quality requirements for well-established tumor markers and tumor markers being developed by use of new technologies (Table 2⇓ ). With its wide scope, this project is one of the most comprehensive and complex of its type to date. The draft guidelines were posted on the NACB website in July 2005 and were presented as an EduTrak at the 2005 Joint AACC/IFCC Annual meeting in Orlando, Florida. Informed comment was also actively sought from individuals, organizations, and other interested parties. View this table: Table 1. Steering committee for NACB Laboratory Medicine Practice Guidelines on Use of Tumor Markers in clinical practice. View this table: Table 2. Subjects and subcommittee members for NACB Laboratory Medicine Practice Guidelines on Use of Tumor Markers in clinical practice. Nineteen subcommittees developed draft guidelines (Table 2⇑ ). Subcommittee members included individuals with extensive expertise in the science, technology, and clinical practice …

Melatonin may protect against breast cancer. Light and other factors influence melatonin, but the evidence is limited. The authors conducted a study to determine factors related to melatonin. Women volunteers recruited in Toronto, Canada, from 2002 to 2004 collected urine for three nights (winter and summer), took periodic light measurements, and recorded exposures in a diary. The relation of each variable to log-transformed creatininecorrected 6-sulfatoxymelatonin in overnight urine was determined by use of generalized estimating equation linear regression. The final model was based on 1,054 measurement days from 213 participating women. None of the light variables was related to the log of 6-sulfatoxymelatonin. A significant interaction between season and day length was included in the final model. The most significant factor was duration of exercise (b ¼ 0.072; p ¼ 0.004, two-tailed), which increased the amount of melatonin produced. Exercise duration later in the day was more significant (b ¼ 0.108; p ¼ 0.0009, two-tailed). There was no difference between moderate or strenuous exercise. The failure to find a relation between light brightness and melatonin may be due to the difficulty of measuring this, as well as the importance of the light spectrum, which could not be measured. It is possible that the protective effect of exercise with respect to breast cancer may operate in part through an effect on melatonin. breast neoplasms; exercise; light; melatonin; women