Researchers led by Xavier Correig from the Universitat Rovira i Virgili in Tarragona, Spain, report in Clinical Chemistry that there is metabolic heterogeneity in polycystic ovary syndrome. Using a GC-MS-based metabolomics approach, the researchers examined plasma samples from 36 women with PCOS and 39 women without it. The cases and controls were matched for age, body mass index, and obesity. The researchers found that PCOS patients were, as compared to controls, hyperinsulinemic and insulin resistant. Obese PCOS patients also had higher levels of long-chain fatty acids and glycerol in their plasma, while non-obese patients with PCOS "showed a metabolic profile consisting of suppression of lipolysis and increased glucose utilization," the researchers report. The further conclude: "Our results indicate substantial metabolic heterogeneity in PCOS, suggesting that insulin resistance and hyperinsulinemia contribute to the pathogenesis of this disorder, but that the latter is not necessarily secondary to the former."

Also in Clinical Chemistry, the University College London Institute of Child Health's Lyn Chitty and colleagues describe their use of digital PCR to detect sickle cell anemia in fetuses from cell-free fetal DNA in maternal plasma. They report that their relative mutation dosage-based approach could correctly identify sickle cell genotype in 82 percent of male fetuses and 75 percent of female fetuses. "We have extended the use of RMD for single-gene disorders to include the prenatal diagnosis of sickle cell anemia, and, for the first time, we have applied this approach to the detection of an autosomal recessive disease in female fetuses," Chitty and her colleagues write.

Researchers in Germany present a dual-color ERG break-apart assay that uses both chromogenic in situ hybridization and silver in situ hybridization in the Journal of Molecular Diagnostics. They compared their approach to detecting the TMPRSS2-ERG fusion gene with fluorescence in situ hybridization. "Our findings demonstrate that the ERG rearrangement status can reliably be assessed by CS-ISH," the researchers write. "Further, the CS-ISH technique combines the accuracy and precision of FISH with the ease of bright-field microscopy."

Also in the Journal of Molecular Diagnostics, researchers at the University of Texas MD Anderson Cancer Center introduce their high-resolution melting-based method to identify DNA methyltransferase 3A mutations in acute myeloid leukemia patients. With this approach, the researchers examined 104 AML patients for mutations in exons 8 through 10 and 15 through 23, which encode the proline-tryptophan-tryptophan-proline, ATR-DNMT3-DNMT3L zinc finger, and MTase domains of DNMT3A and compared it to Sanger sequencing. "On the whole, the 0% false-negative and relatively low false-positive rates make HRM a very reliable screening method for DNMT3A mutations and drastically decreases the number of samples requiring direct sequencing," they write.

Researchers at the University of Belgrade in Serbia examined genomic instability and p53 changes in anaplastic astrocytoma and primary glioblastoma patients. As they report in Experimental and Molecular Pathology, they used arbitrarily primed PCR to detect both chromosomal instability and the accumulation of mutations in tumors and found that about 40 percent of tumors had p53 alterations while 63 percent had high levels of genomic instability. "Our results, although limited by a relatively small set of samples, suggest that high overall level of genomic instability is one of the main features of anaplastic astrocytomas and primary glioblastomas. Alterations of p53, although frequently present, did not show any association with the level of genomic instability, but were associated with anaplastic astrocytomas," the researchers write.

Also in Experimental and Molecular Pathology, researchers led by Devendra Agrawal from the Creighton University School of Medicine write that high levels of vitamin D receptors in mucosa of people with Barrett's Esophagus "may indicate an increased sensitivity of this tissue to endogenous or therapeutic effects of Vitamin D."

Researchers in London report in the Journal of Clinical Pathology that expression of Ki-67, a protein that is present during active phases of the cell cycle, is a moderate marker for human papillomavirus infection in penile squamous cell carcinoma. The researchers examined 148 formalin-fixed, paraffin-embedded penile squamous cell carcinoma samples for Ki-67 expression and presence of HPV. They found that Ki-67 was strongly expressed in nearly 40 percent of the samples and that Ki-67 expression was "positively correlated with high-risk HPV," and with tumor grade. "High Ki-67 immunoexpression could be an indicator, but not a definitive predictor of high-risk HPV infection in PSCC," the researchers write, adding that expression does not correlate with lymph node metastasis, cancer-specific survival, or overall survival.

Also in the Journal of Clinical Pathology, researchers led by the University of Vienna's Sebastian Schoppmann write that the human homolog of CUL-4, which is important in DNA replication in Caenorhabditis elegans, is associated with the development and progression of ovarian carcinoma. CUL-4 is known to interact with cell cycle regulators like p53 and p21. The researchers studied CUL-4, p53, and p21 protein expression in 140 human epithelial ovarian tumor samples, and found that CUL-4 overexpression is associated with overall and disease-free survival in invasive carcinoma. "Our results show that CUL-4 is associated with the malignant potential of ovarian tumors. It might also play a relevant role in the progression of ovarian carcinoma, warranting further investigations," the researchers write, adding that "interestingly, no association of CUL-4 with p53 and p21 expression was found."

Researchers from University Hospital Zurich report their 10-year follow-up study on diagnostic errors in Modern Pathology. The researchers previously examined diagnostic errors between 1972 and 1992, and for this study, they looked at differences between clinical diagnoses and those made at autopsy for 100 patients who died at a teaching hospital in Switzerland in 2002. They found that during the last 30 years, major diagnostic errors declined from 30 percent to 7 percent while sensitivity for diagnosing cardiovascular, infectious, and neoplastic diseases increased, and specificity for diagnosing cardiovascular diseases increased. Additionally, the researchers note that the number of diagnostic procedures performed have increased over the years. "The frequency of major diagnostic errors has been further reduced at the beginning of the new millennium probably due in large part to new diagnostic tools," they write.

Thomas Wiesner from the Medical University of Graz in Austria and his colleagues report evidence in Modern Pathology for a morphological variant of superficial spreading melanoma, which they call 'melanomas composed exclusively or predominantly of large nests,' or MLNs. The researchers histologically and genetically characterized 11 MLNs, finding that they have a "predominant arrangement of melanocytes in very large nests" that conventional superficial spreading melanoma lacks, and that "all of the tumors in this study showed multiple gains and losses of several chromosomes," similar to conventional superficial spreading melanoma.

Laboratory Corporation of America is acquiring Medtox Scientific for about $241 million, says a press release from the companies. Medtox offers clinical laboratory services including toxicology testing and bio-analytical testing for clinical trials, among other things. "This transaction highlights the fundamental value of the Medtox brand, the talent and expertise of our team and the quality of our products and testing services," says Dick Braun, the company's chairman and CEO. "As part of LabCorp with its substantial resources and infrastructure, we expect to accelerate Medtox's profitable growth and provide a stable and sustainable environment for our employees and clients."