Global Biosafety

Inspections of biocontainment labs in the Asia-Pacific region have revealed problems that would shut down similar labs in the West, says Nature News. A report on the inspection, co-sponsored by the Asia-Pacific Biosafety Association, was presented at international affairs institute Chatham House last week. Chatham House associate fellow Nigel Lightfoot tells Nature News that solutions used in the West may not work in developing countries and there might have to be two sets of standards.

The World Health Organization's Nicoletta Previsani says, however, that having different rules won't make either side happy. Some meeting attendees called for the WHO, the Food and Agriculture Organization of the United Nations, and the World Organisation for Animal Health to develop global lab standards. However, other attendees say those organizations may lack the authority and money to act as regulators, Nature adds.

This Week in Modern Pathology

Brazilian researchers report in Modern Pathology on their examination of B-cell lymphoma, unclassifiable, a disease that shares characteristics of both diffuse large B-cell lymphoma and classical Hodgkin lymphoma or has features intermediate to those two diseases. The researchers describe the clinicopathological features of 10 cases of B-cell lymphoma, unclassifiable. "Our findings show a male preponderance, median age of 37 years and a mediastinal presentation in 80 percent of cases. All cases expressed at least two markers associated with B-cell lineage and good response to combination chemotherapy currently employed for non-Hodgkin lymphomas," the authors say.

Ohio State University researchers describe their laser capture microdissection-mass spectrometry approach to characterizing glomerular diseases in Modern Pathology. With this approach, the researchers examined the proteomes of glomeruli from normal kidneys as well as samples from patients with diabetic nephropathy, lupus nephritis, and fibronectin glomerulopathy. They report that disease-associated glomeruli had increased levels of complement proteins, though decreased number of proteins associated with podocytes and cellular metabolism. "The most interesting findings from this study are the newly discovered changes in protein expression. This demonstrates that our approach is a robust platform that may inform disease pathogenesis," the Ohio State researchers write.

Broader Power

Lawmakers in the US may vote this week on legislation that would give the Food and Drug Administration broader authorities and would renew the law governing the user fees that FDA collects to review drugs and medical devices, reports The Wall Street Journal. The Journal notes that both versions of the bill give FDA regulatory authority over foreign raw materials for drugs, as FDA now "has limited ability to require safety inspections of foreign drug facilities." Additionally, under the law, drug companies would pay about 6 percent more in user fees, or $4 billon over five years, and medical device companies would see a doubling in fees to $600 million over five years, the report adds.

This Week in Clinical Chemistry

Researchers led by Catherine Alix-Panabières from Saint-Eloi Hospital in Montpellier, France, report in Clinical Chemistry that current approaches for detecting circulating tumor cells can pick up circulating epithelial cells in patients with benign colon disease. They analyzed peripheral blood from 53 patients with benign colon diseases — such as diverticulosis or Crohn's disease, among others — and analyzed it using CellSearch and CK19-EPISPOT. CellSearch identified circulating tumor cells in 11.3 percent of the patients and EPISPOT found circulating tumor cells in 18.9 percent of the patients; the researchers note that after three years of follow up, no patients were diagnosed with colorectal cancer. "This finding points to the need for further molecular characterization of circulating epithelial cells and has important implications for the use of CTC testing," Alix-Panabières and colleagues write.

FFA Sciences' Andrew Huber and colleagues describe a fluorescence sensor that they have developed to measure free-form bilirubin in plasma. As they report in Clinical Chemistry, their method relies on a fluorescently labeled mutated fatty acid binding protein whose fluorescence is quenched upon binding bilirubin. "The BL22P1B11-Rh probe provides accurate plasma sample Bf concentrations with a single measurement, in one minute with either a handheld Bf meter or a laboratory fluorometer," Huber et al. write.

This Week in the Journal of Molecular Diagnostics

Researchers led by Weill Cornell Medical College's Hanna Rennert report in the Journal of Molecular Diagnostics that long-range PCR is better than direct sequencing and screening for evaluating PKD1 and PKD2 mutations in polycystic kidney disease. They found that their approach of sequencing LR-PCR fragments covering the PKD1 gene had a sensitivity of 100 percent, a specificity of 98.5 percent, and an accuracy of 98.8 percent when compared to direct sequencing done by a reference laboratory, and a sensitivity of 97.1 percent, a specificity of 100 percent, and an accuracy of 99.4 percent when compared to the Surveyor-Wave Nucleic Acid High Sensitivity Fragment Analysis System from Transgenomic. "The LR PCR sequencing method has several advantages for the detection of PKD gene variants, including high sensitivity, improved intronic coverage, faster turnaround time, and lower cost, providing a reliable tool of genetic analysis of complex genes and repetitive sequences," Rennert and her colleagues write.

Also in the Journal of Molecular Diagnostics, researchers from Johns Hopkins University School of Medicine report using a DNA sequencing approach to identify filamentous fungi — they used a SmartGene approach to target the D1/D2 region of the large subunit of the 28S rDNA gene and the ITS region of the fungi for identification. Additionally, they assessed the accuracy of that approach and of using the SmartGene proofreaders and database. "The SG software and database is an acceptable tool to be used in a clinical laboratory for fungal DNA sequencing analysis. It is anticipated that this will allow clinicians to choose more appropriate antifungal therapy based on organism identification, resulting in improved patient outcomes," they say.

An Accreditation Module

The College of American Pathologists is teaming up with SoftTech Health to "bring state-of-the-art accreditation management tools to clinical laboratories worldwide," a SoftTech press release says. The organizations are combining CAP's clinical lab guidelines with SoftTech's quality management software to create an accreditation checklist module that can be inserted into SoftTech Health's LabQMS Quality Management Software system, or other document management systems. "The objective of the SoftTech Health/CAP Partnership enables laboratories' regulatory compliance efforts to be strengthened and supported, ultimately improving the quality of patient care," the organizations say in a statement.

A Decline for Vermillion

Molecular diagnostics company Vermillion reported this week that its first-quarter 2012 revenues fell 28 percent as compared to 2011, according to a company press release. Vermillion reported $198,000 in sales of its OVA1 ovarian cancer diagnostic for Q1, down from $317,000 for Q1 of 2011. The company notes that the prior-year Q1 OVA1 revenue includes $158,000 in deferred 'true-up' payments from Quest Diagnostics. The volume of OVA1 sales increased 28 percent, as compared to 2011, to 3,952.

Our sister publication ProteoMonitor adds that during conference call on the Q1 results, Vermillion CEO Gail Page said that the company has "implemented several initiatives that will lead to regaining our growth trajectory." ProteoMonitor adds that Page plans to leave the company by September.

This Week in Experimental and Molecular Pathology

The University of California, Davis' Kiho Cho and his colleagues report in Experimental and Molecular Pathology that structural changes occur in the mouse genome that are age-dependent as well as tissue-specific. Cho and his team examined such changes in conjunction with retroelement transposon activity, and found that liver genomes were larger than ones isolated from other organs and that genome size peaked around five weeks of age. "The data from this study provided evidence that there are multiple variant alleles/isoforms of the genome from an individual in association with age and tissue type," they write. "Thus, a new protocol/system, which addresses the dynamic property and/or multiplicity of the genome, needs to be developed to decode and establish the personal genome."

Researchers from Creighton University School of Medicine in Omaha, Neb., report in Experimental and Molecular Pathology that vitamin D receptor expression may be related to esophageal adenocarcinoma tumor progression and response to therapy. They examined 15 samples from patients being treated for esophageal adenocarcinoma and found that elevated expression of vitamin D receptor correlated with tumor non-response to neoadjuvant therapy and decline with de-differentiation of tumors. However, the researchers note that while "it is plausible that the extent of VDR expression is related to tumor progression and response to therapy, ... it is equally as plausible that these data are merely random."

Disease Uncovered

Next-generation sequencing can be used to detect and diagnose minimal residual disease in patients with T-lineage acute lymphoblastic leukemia/lymphoma, report researchers led by Harlan Robins at the Fred Hutchinson Cancer Research Center. Using 43 matched pairs of T-ALL samples, the researchers compared the abilities of next-gen sequencing and multiparametric flow cytometry to detect minimal residual disease and found that sequencing was equivalent to or better than flow cytometry, as they report in Science Translational Medicine. "Our research indicates that HTS [high-throughput sequencing] offers many advantages over flow cytometry," Robins says in a statement. "Since HTS can detect any pre-identified clone and is performed in a centralized lab, it consistently generates reproducible and reliable results regardless of cancer type, using the same process for disease detection and tracking. Furthermore, HTS is highly automated, cost-effective and objective, whereas flow cytometry is more time consuming, relies on the skill of the operator and is therefore subject to human error."

The press release adds that the Hutchinson Center has patents pending on some of the technologies used in this study.

This Week in the Journal of Clinical Pathology

Researchers led by Mauricio Salcedo from the Hospital de Oncologia in Mexico City report in the Journal of Clinical Pathology on NF1 gene expression in sporadic breast cancers. Using a combination of immunohistochemistry, tissue microarrays, and end-point RT-PCR, the researchers examined neurofibromin and RAS expression as well as NF1 and CELF 3-6 RNA expression in sporadic breast cancer, benign lesions, and normal breast tissue. From this, the researchers report that NF1 was expressed in both early- and late-stage tumors, though they note that the isoforms differ between benign and cancerous tissue. "The NF1 expression shift transition of the type II to type I isoforms in breast cancer could be a significant event in the development and progression of sporadic breast cancer, as well as in other human cancers, and that this trend could possibly represent a potential molecular marker in several different cancer types," Salcedo and his colleagues write.

Also in the Journal of Clinical Pathology, a team of researchers in Vancouver presents a method for determining serum aldosterone levels using liquid chromatography and tandem mass spectrometry. The team used AbSciex's API5000 system and a liquid-liquid extraction approach, which it found to have a coefficient of variation that is "comparable with or better than previous reports." The researchers add that "the strength of this method lies in its simplicity and affordability," though they note that the approach has its weaknesses — namely that it needs larger sample volumes and time between injections.

The Same Team

Lab professionals find that teaming up with pharmacists "can enhance the value and efficiency of both lab tests and drugs," writes Bill Malone at Clinical Laboratory News. Malone adds that while the role of the lab in pharmacogenomics is much addressed, there is another sort of personalized medicine in which lab professional can help — monitoring patients on new drugs, particularly anticoagulants, and patients with chronic disease. Jim Carlson, the director of pharmacy health plan services at Group Health Cooperative in Seattle, Wash., says labs need to emphasize how patient outcomes will be improved. "This is what will really speak to the pharmacy folks," he tells Malone. "They went into pharmacy in order to help patients, and my feeling is that most would be open to hearing from other healthcare professionals about collaborative opportunities to actually improve patient care."

This Week in Modern Pathology

Researchers from the University of Texas MD Anderson Cancer Center report in Modern Pathology that immunohistochemistry is better for detecting PTEN loss than gene sequencing in endometrial carcinoma. They compared PTEN immunohistochemistry and PTEN sequencing of 154 endometrioid and non-endometrioid endometrial carcinomas to see which approach was best for determining PTEN loss. "We demonstrate a detailed correlation between PTEN sequencing abnormalities and PTEN immunohistochemistry," the researchers write. "PTEN immunohistochemistry is able to identify the majority of cases with genetic PTEN loss and also detects additional cases with functional PTEN loss otherwise undetected by mutational analysis."

Also in Modern Pathology, a team of researchers from Northwestern University and the Ontario Cancer Institute describes its examination of the role of the aldo-keto reductase family 1B10, or AKR1B10, in pancreatic adenocarcinoma. The team evaluated AKR1B10 expression in 50 paraffin-embedded clinical pancreatic cancer samples and found that it is "significantly increased in precursor lesions and infiltrating adenocarcinomas of the pancreas." Further, the team reports that AKR1B10 knockdown "was associated with increased apoptosis, decreased protein prenylation, and decreased activation of KRAS and several of its downstream effectors." The team adds that AKR1B10 inhibition "and subsequent inhibition of protein prenylation including KRAS and its downstream pathway, as well as the induction of cell apoptosis, may serve as a highly promising target for future studies focusing on the development of treatment modalities and prevention strategies."

A View on the Medical Device Tax

The tax on medical devices that is part of the US Affordable Care Act will harm companies and American workers, writes Henry Miller from Stanford University and the Competitive Enterprise Institute in an op-ed at The Wall Street Journal. The 2.3 percent tax is slated to go into effect at the end of the year. "This tax is especially pernicious because it is assessed on sales, not profits," Miller says, describing a hypothetical situation in which a medical device company with $1 million in sales would be taxed $23,000, even if its profit was $100,000. Miller says companies are already taking defensive precautions in anticipation of the tax, like announcing layoffs. "We need to create a more nurturing entrepreneurial climate, one in which ingenuity and innovation are rewarded, not penalized," he adds.