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A clinical lab at Ohio State University's medical center mishandled proficiency examples and has been told by the Centers for Medicare and Medicaid Services that it is in "immediate jeopardy," reports The Columbus Dispatch. The paper adds that the lab sent out proficiency test samples to another lab for confirmation, which it notes is not allowed. Ohio State notes that the error was caught by lab administrators and was reported by them to CMS; the school is also filing an appeal. "Once CMS reviews this additional information, Ohio State is confident that the government's concerns will be addressed," the school added in a statement.

This Week in Modern Pathology

Magee-Womens Hospital of UPMC's Rohit Bhargava and colleagues report in Modern Pathology that "immunohistochemistry is preferable to qRT-PCR for determination of estrogen and [progesterone receptor] expression." The researchers analyzed 464 breast cancer cases for ER and PR status using both immunohistochemistry and Genomic Health's Oncotype DX assay. They found good correlation between both approaches, though they write that immunohistochemistry was slightly more sensitive. "Immunohistochemistry offers additional advantages such as lower expense, ease of use, and faster turnaround time, the researchers say, later adding that "as qRT-PCR requires tissue microdissection and grinding for analysis, samples are inherently at risk for contamination with normal ductal breast tissue, fibroadipose tissue, inflammatory cells, biopsy cavities, and in situ carcinoma.

Also in Modern Pathology, researchers led by Oncolytics Biotech's Matthew Coffey examine the correlation between reovirus infection and cancer cell death. Using RT in situ PCR, the researchers found that, in patients treated with reovirus, most cancer cells harbored the viral genome. Further, they report that related cancer cell death is due to viral inhibition of microRNA-let-7d. "A key reason reovirus may be effective in destroying cancer cells is that the productive viral infection basically functions as an acute 'anti-microRNA' therapy," Coffey and colleagues write. "That is, the proliferating viral genome can acutely and markedly reduce microRNA-let-7d that, in turn, bypasses the normal 'caspase-apoptosis cascade' by markedly increasing the expression of caspase-3, that is the principle caspase responsible for the apoptotic death of these cancer cells."

Safety First

Drawing on its annual lab safety survey, Lab Manager Magazine says that safety practices in the lab are improving. Most of the 464 respondents worked in college or university settings, followed by clinical labs, and about half of respondent worked in labs with fewer than 10 people. A few highlights:

96 percent of respondents said their chemical and lab safety manuals were current and accessible to workers, compared to 92 percent in 2011
32 percent said that their labs conducted safety inspections annually, while 30 percents reported monthly inspections
Eleven of 18 general safety management practice categories showed improvement compared to 2011

"As this year's lab safety survey reveals, lab safety practices continue to improve for the most part, though not to the same degree as was reported from 2010 to 2011. We can only hope that the upward trend continues, no matter how small the percentage increases," Lab Manager Magazine adds.

This Week in Clinical Chemistry

Researchers at Catharina Hospital in The Netherlands report in Clinical Chemistry that variations in cardiac troponin levels determined by new, highly sensitive assays can identify emergency room patients with acute myocardial necrosis. They examined short-term differences in cardiac troponin in emergency department patients using Roche Diagnostics' high-sensitivity cardiac troponin T assay and Siemens Diagnostics' sensitive cTnI assay. "The short-term variations and IIs of cardiac troponin were low in ED patients free of ischemic myocardial necrosis," they report, adding that they advise using cut-off values of 8 ng/L for the hs-TnT assay and 17 ng/L for the cTnI assay. "With the use of this approach," the team adds, "the time between arrival and appropriate management may be shortened and the strain on ED capacity decreased."

Also in Clinical Chemistry, Kai Wollert from Hannover Medical School in Germany and colleagues discuss their use of expression cloning to find a prognostic biomarker for acute coronary syndrome. The researchers developed an expression screen to look for genes that encode activators of the GDF15 promoter. GDF15 is a stress-response cytokine whose expression is linked to prognosis in acute coronary syndrome. From their screen, the researchers found that secreted protein follistatin-like 1, or FSTL1, induces GDF15 expression and is independent biomarker for ACS prognosis. "Our study is the first to use expression cloning for biomarker discovery upstream of a gene of interest, a strategy that will be applicable outside the specific example provided here," they add.

Growth for Bio-Reference Laboratories

Bio-Reference Laboratories grew their second-quarter revenue by almost 19 percent, reports the Associated Press. The company announced $163.4 million in sales for that quarter, up from $137.7 million in 2011. "During the first six months of this fiscal year, we introduced several initiatives based on innovative technologies and innovative reporting techniques that we believe will enable us to continue our growth. OnkoMatch, Inherigen, and GenCerv are now being introduced to physicians around the country by our national sales force," said CEO Marc Grodman in a statement. He added, "For many years, our growth was driven by our expansion in the esoteric markets; which in turn creates greater opportunities for growth in all of our clinical offerings. We continue to be paced by esoteric growth, but we have also been able to expand routine clinical testing into those same physician offices and have been able to achieve a more stable position in the physicians' offices."

This Week in the Journal of Molecular Diagnostics

Researchers led by Brown University's Anubhav Tripathi present their simple method for amplifying, and detecting, RNA targets, or SMART, in the Journal of Molecular Diagnostics. SMART relies on mirofluidics and a modified nucleic acid sequence-based amplification approach. Using a synthetic influenza target, Tripathi and his team demonstrated that the SMART assay could capture its target. "This platform is clinically relevant, given that the probes presented were based on sequences shown to hybridize to full-length influenza A H5 vRNA," the researchers write. "Additionally, because of the flexibility of the amplifiable probe sequence, this method can easily be used for detection of any number of RNA targets."

Also in the Journal of Molecular Diagnostics, George Yousef from St. Michael's Hospital in Toronto and his colleagues report that miR-21 can be used to tell clear cell and papillary renal cell carcinoma apart from chromophobe renal cell carcinoma and oncocytoma. Using real-time quantitative RT-PCR with miR-21-specific probes, Yousef and his colleagues examined miR-21 expression in subtypes of renal cell carcinoma as well as in healthy kidneys. "Our results show that miR-21 is up-regulated in clear cell and papillary subtypes of RCC compared with healthy kidney and benign renal tumors," the authors say, later adding that miR-21 is also a prognostic marker in renal cell carcinoma.

Hard But Necessary

While getting a device through review by the US Food and Drug Administration is difficult, the director of FDA's Center for Devices and Radiological Health Jeffrey Shuren is making the process faster and smoother, reports The Commercial Appeal, a Memphis, Tenn.-based newspaper. Shuren put guidelines in place to make the review process more efficient, and clearer to applicants. The Commercial Appeal adds that executives from BioNanovations say that the "the FDA approval process is tough, but necessarily tough" and that explanatory websites have been helpful. BioNanovations's Andre Simmons says tells the paper that it is a difficult process "because they want to protect everybody."

Now Open

Since the end of 2010, the MIT Medical Lab has been undergoing renovations, and its newly re-done space has passed inspections and is open, according to MIT News. While the disruption was hardly noticed by patients, lab manager Jane Sylvester says that lab workers had to make trips from one side of the street to the other to bring samples from the phlebotomists — who remained in a space near to the lab undergoing renovations — to the temporary lab. "Delivering samples was part of going to lunch," Sylvester tells MIT News. For rush samples, she adds, "phlebotomists would bring the sample right over if they could get away, or a lab tech would run over to pick it up. Often they'd end up doing a handoff in the middle of the street."

The renovated lab has new equipment and an additional 10 square feet of bench space; the lab can also increase the number of tests it offers.

This Week in Experimental and Molecular Pathology

Researchers at the Catholic University of Korea report in Experimental and Molecular Pathology that denaturing high-performance liquid chromatography is a "sensitive, specific, and accurate method for detecting the BRAFV600E mutation" that occurs in many papillary thyroid carcinomas. The researchers compare the accuracy and efficiency of DHPLC in detecting the mutation in FFPE samples to that of direct sequencing, pyrosequencing and colorimetric assay. They report that DHPLC had 100 percent sensitivity, specificity, and accuracy. "In addition, it is rapid, simple, easy to perform and usable to screen a large number of samples for clinical diagnostic application," the researchers write.

Also in Experimental and Molecular Pathology, a team at Johns Hopkins Hospital presents its investigation of the utility of LMP2, a subunit of an immunoproteasome, as a diagnostic marker of renal cancer. The immunoproteasome is overexpressed in thyroid cancer, and as renal oncocytic tumors are morphologically similar to thyroid gland oncocytic lesions, the team looked into LMP2 expression in renal cancer. It reports that nuclear expression of LMP2 can distinguish renal oncocytomas from chromophobe renal cell carcinomas. "These results suggest that the nuclear LMP2 expression can be used in clinical scenarios where histological distinction between RO and CHRCC-EO remains challenging," the researchers write.

A Shift Up

GenMark Diagnostics has revised its revenue estimates for the second quarter of 2012 and for the calendar year, the company says in a press release. For the second quarter, the company now projects it will have between $3.2 million and $3.6 million in revenue for Q2 and more that $15 million for the full year. In a statement, company President and CEO Hany Massarany attributes this increase to increased test utilization and "anticipated growth from near-term future menu.

The Sample's sister publication GenomeWeb Daily News has more here.

This Week in the Journal of Clinical Pathology

Researchers led by Akitaka Nonomura at the Nara Medical University School of Medicine in Japan examine the role of EGFR in malignant mesothelioma. As they report in the Journal of Clinical Pathology, the researchers evaluated EGFR mutations in 38 malignant mesothelioma patients using a combination of immunohistochemical staining, FISH analysis, and direct sequencing of certain exon regions. From this, Nonomura and colleagues found in six patients five missense mutations in EGFR, two of which were novel. "Our study confirmed that EGFR overexpression is a common feature in MM, especially the epithelial subtype," the researchers write. "The protein overexpression of EGFR was not related to a gene copy-number gain. To select candidates for anti-EGFR therapy among MM patients, further and larger studies will be needed."

Also in the Journal of Clinical Pathology, Alex Liao from the Chi-Mei Foundation Medical Center in Taiwan and colleagues report that overexpression of Rsf-1 is linked to higher tumor stage and poorer outcomes in urothelial carcinoma of the urinary bladder. Using immunohistochemical, real-time RT-PCR, FISH, and western blot analysis, combined with clinicopathological data, the researchers "demonstrated that Rsf-1 expression correlates with the adverse clinicopathological features of UCUB, and confers a significant survival determinant in both disease-specific and MeFSs," they write." More importantly, its overexpression seems to be less likely associated with RSF1 gene amplification."

Into the Field

The Ottawa Hospital is looking to move into personalized medicine with a new molecular diagnostics lab, reports The Ottawa Citizen. The lab is still in the planning stage and the hospital needs to raise seed money, but the hospital says such a lab would bring DNA sequencing closer to being part of standard patient care. "This is a very realistic vision, and I want Ottawa to be positioned as a provincial centre of excellence for molecular diagnostics," says Paula Doering, the hospital's vice president of clinical programs.

This Week in Modern Pathology

Researchers at University Hospital Zurich in Switzerland report in Modern Pathology that the loss of BAF250a expression in endometriosis may indicate that it will transform into cancer. The researchers examined BAF250a expression in endometriosis, endometrium, and ovarian cancer samples. "We corroborate that BAF250a expression deficiency in endometriosis is not restricted to tumor contiguous lesions and that loss of BAF250a expression can be observed already in benign endometriotic lesions, and could therefore indicate a risk of malignant transformation," they add.

Also in Modern Pathology, researchers led by Hôpital Saint-Louis' Anne Janin write that expression of BCL2 by CD105+ neoangiogenic endothelial cells is linked with tumor progression in angioimmunoblastic T-cell lymphoma. Using a combination of triple immunofluorescence and quantitative real-time PCR, Janin and her colleagues found that "BCL2 and VEGFA proteins were coexpressed in endothelial and lymphoma cells of the 30 angioimmunoblastic T-cell lymphoma cases" that they examined but that "a significant relation between BCL2 and VEGFA mRNA levels was only found in endothelial cells." They add that BCL2 mRNA levels "correlated with microvessel density, International Prognostic Index, Ann Arbor stage, bone marrow involvement and elevated LDH."