Enzo Biochem announced earlier this week that it has filed an application with the New York State health department for approval of its first assay, which is based on its nucleic acid detection platform called AmpiProbe. The assay for which the company is seeking approval, HCV RNA Quantification Assay, determines viral load. "We view [AmpiProbe HCV] as potentially a promising example of other molecular-based products that we currently have under development," said Enzo President Barry Weiner in a statement.

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University of Pittsburgh Medical Center's Xinhui Wang and colleagues report in Modern Pathology on their evaluation of ALDH1A1 expression in breast cancer as a prognostic marker. The researchers studied 513 breast cancer cases, and found that ALDH1A1 was expressed in 10 percent of the cases. Of those, 45 percent were triple negative and 32 percent were HER2+. In addition, ALDH1A1 was found most often in stage 3 cases. "We conclude that ALDH1A1 correlates with triple-negative and HER2+ breast cancers. It is also correlated with advanced stage and lymph-node status," the authors write. "More importantly, ALDH1A1 could be used as a predictor biomarker for worse clinical outcome in patients treated with cytotoxic neoadjuvant therapy that includes cyclophosphamide and have substantial RCB [residual cancer burden]."

Also in Modern Pathology, the University of California, Los Angeles' Stephen Koh and his team examine differential gene expression in primary cutaneous melanoma and sentinel lymph node metastases. The researchers performed whole genome expression profiling on 10 primary melanomas and nine sentinel lymph node metastases. "Among the 576 genes that distinguished primaries and metastases, most genes that were associated with metastases (402) showed decreased expression relative to the primary lesions," Koh et al. write, later adding that "despite inter-observer variations, it is clear that there are substantial differences in gene expression between melanomas at different stages of progression, in this study, between primary melanomas and melanoma metastases in sentinel nodes."

Harvard Medical School's Mike Makrigiorgos and his colleagues report in Clinical Chemistry that coamplification at lower denaturation temperature — or COLD — PCR could enrich rare mutations better than conventional PCR for identification using next-generation sequencing. The researchers used both COLD-PCR and conventional PCR to amplify lung adenocarcinoma DNA, colorectal cancer DNA, and wild-type DNA that was then sequenced using the Ilumina HiSeq 2000. "In the described approach, we observed that the mutational status after COLD-PCR exceeded errors and artifacts appreciably and enriched genuine low-abundance mutations, thereby allowing accurate detection of clinically relevant mutations without the need for extensive data manipulation," Makrigiorgos and his team write.

In an online early article at Clinical Chemistry, researchers led by Ann Gronowski at Washington University School of Medicine report that the addition of microRNAs associated with pregnancy to a diagnostic panel containing human chorionic gonadotropin and progesterone improved the accuracy of ectopic pregnancy diagnoses. "This proof-of-concept study is the first to examine the relationship between pregnancy-associated miRNAs and early pregnancy outcomes, and it is the first to explore the diagnostic value of miRNAs for EP [ectopic pregnancy]," Gronowski and her colleagues write. "Given that miRNA molecules are highly stable in circulation, they are more robust and more suitable for serving as blood-based biomarkers than some protein or peptide-based markers."

In a paper published online in advance in the Journal of Clinical Pathology this week, researchers at University Hospital in Modena, Italy, report having evaluated the "association between tumor grade, hormone receptor status, proliferation index (Ki67) and FISH [fluorescence in situ hybridization] amplification, using both US Food and Drug Administration and American Society of Clinical Oncologists/College of American Pathologists cut-offs" in 480 HER2 2+ breast cancer samples. Overall, the researchers found that "high tumor grade and high Ki67 significantly predicted FISH amplification" in the samples.

In another online first article published this week, investigators in Finland and Japan evaluate the expression of claudins 7 and 18 in 111 samples and 47 additional biopsy samples of pancreatic ductal adenocarcinoma. Overall, these samples consisted of 26 cases of pancreatitis, three cases of pancreatic intraepithelial neoplasia and 18 ductal adenocarcinomas. The team stained the samples with antibodies to both proteins to analyze both membranous and cytoplasmic expression, finding that "well-differentiated pancreatic adenocarcinomas displayed more cases with membrane-bound claudin 7 or 18 immunopositivity," and that "all pancreatic intraepithelial neoplasias … expressed membrane bound claudin 18." In addition, the team shows that "membrane-bound claudin 7 or 18 positivity was not associated with survival."

Researchers led by the University of Texas MD Anderson Cancer Center's Jinsong Liu report in Modern Pathology that expression of CD133 predicts poor outcome in patients with ovarian cancer. The researchers examined CD133 expression and its correlation with clinical factors, disease-free survival, and overall survival in 400 patients with ovarian carcinoma. "CD133 expression was associated with high-grade serous carcinoma, late-stage disease, ascites level, and shorter overall survival and disease-free survival time," they write. Further, the researchers note that CD133 is thought to be expressed by tumor-initiating cells, a theory they say their results support.

Also in Modern Pathology this week, Johns Hopkins Medical Institutions' Aatur Singhi and his colleagues write that MYC amplification is important in breast cancer progression and metastasis. The researchers analyzed MYC copy number and protein expression in primary breast cancers and matched metastases, and found that "gains in MYC copy number are a frequent event in breast cancer and occur relatively late in tumorigenesis." They add, "These observations underscore the importance of MYC in breast cancer progression/metastasis, as well as its relevance as a potential therapeutic target in otherwise incurable metastatic disease."

Researchers led by Daniel Wagner at Centre Hospitalier Luxembourg report in the Journal of Clinical Chemistry that circulating microRNAs are strong markers of heart attack. In their case-control study of 510 myocardial infarction studies, the researchers found that the cardiac-enriched miRNAS miR-208b and miR-499 were "highly increased" in MI patients, as determined by qPCR. The researchers also note, however, that "their usefulness in the establishment of a rapid and accurate diagnosis of acute MI remains to be determined in unselected populations of patients with acute chest pain."

Also in the Journal of Clinical Chemistry, researchers in Hong Kong discuss their examination of molecular size difference in plasma DNA that is hematopoietically or non-hematopoietically derived. Using massively parallel paired-end sequencing, the researchers determined the fragment length of plasma DNA from six hematopoietic stem cell transplant recipients and one liver transplant recipient. "Plasma DNA molecules exhibit a distinct fragmentation pattern, with the nonhematopoietically derived molecules being shorter than the hematopoietically derived ones," the authors write.