The Journal of Molecular Diagnostics

Our medical research library holds 7 studies published in The Journal of Molecular Diagnostics (2000–2021). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 7 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Elsevier
• Published: 1999 to the present, United States
• Language: English
• ISSN: 1525-1578 (print), 1943-7811 (electronic)
• Its record in the NLM Catalog

2020s

• DNA Methylation Profiling Discriminates between Malignant Pleural Mesothelioma and Neoplastic or Reactive Histologic Mimics. L. Bertero, L. Righi, G. Collemi, et al. 2021;23(7):834-846. PubMed · Publisher

  Abstract

  The diagnosis of malignant pleural mesothelioma (MPM) is challenging because of its potential overlap with other neoplasms or even with reactive conditions. DNA methylation analysis is effective in diagnosing tumors. In the present study, this approach was tested for use in MPM diagnosis. The DNA methylation patterns of a discovery cohort and an independent-validation cohort of MPMs were compared to those of 202 cases representing malignant and benign diagnostic mimics (angiosarcoma, desmoid-type fibromatosis, epithelioid sarcoma, leiomyosarcoma, lung adenocarcinoma, lung squamous cell carcinoma, melanoma, nodular fasciitis, reactive mesothelial hyperplasia, sclerosing fibrous pleuritis, solitary fibrous tumor, and synovial sarcoma). By both unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding analysis, MPM samples in the discovery cohort exhibited a DNA methylation profile different from those of other neoplastic and reactive mimics. These results were confirmed in the independent validation cohort and by in silico analysis of the MPM-The Cancer Genome Atlas data set. Copy number variation profiles were also inferred to identify molecular hallmarks of MPM, including CDKN2A and NF2 deletions. Methylation profiling was effective in the diagnosis of MPM, although caution is advised in samples with low tumor cell content.

  Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

• Differential Diagnosis of Malignant Pleural Mesothelioma on Cytology: A Gene Expression Panel versus BRCA1-Associated Protein 1 and p16 Tests. R. Bruno, G. Alì, A.M. Poma, et al. 2020;22(4):457-466. PubMed · Publisher

  Abstract

  Pleural effusions are among the first clinical manifestations of malignant pleural mesothelioma (MPM) and often constitute the only available material for diagnosis. Although an MPM diagnosis can be reliable on cytology, the reported sensitivity is low (30% to 75%). Particularly, it can be hard to discriminate epithelioid MPM, the most common histotype, from reactive mesothelial hyperplasia (MH). Currently, BRCA1-associated protein 1 (BAP1) and CDKN2A (p16), evaluated by immunohistochemistry and fluorescent in situ hybridization, respectively, are the most valuable markers to discriminate MPM and MH. Both markers have a high specificity, but their sensitivity is not always satisfying, even when used together. We have recently developed a 117-gene expression panel, based on Nanostring technology, able to differentiate epithelioid MPM from MH pleural tissues better than BAP1 and p16. Herein, we evaluated the efficacy of the same panel on an independent retrospective cohort of 23 MPM and 11 MH pleural effusions (cell blocks and smears). The overall sensitivity and specificity of the panel were equal to 0.9565 and 1, respectively. Moreover, the panel performance was compared with BAP1 and p16 on 25 cell blocks. Sensitivity levels of gene panel, BAP1 alone, p16 alone, and BAP1 plus p16 were 1, 0.5882, 0.4706, and 0.7647, respectively. Specificity was always 1. Although further validation is needed, this gene panel could really facilitate patients' management, allowing a definitive MPM diagnosis directly on pleural effusions.

  Copyright © 2020 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

• Treatment Response Monitoring in Patients with Advanced Malignancies Using Cell-Free SHOX2 and SEPT9 DNA Methylation in Blood: An Observational Prospective Study. L. de Vos, M. Jung, R.M. Koerber, et al. 2020;22(7):920-933. PubMed · Publisher

  Abstract

  Patients with incurable cancer usually receive palliative treatment with significant toxicity and limited efficacy. Methylation analysis of circulating cell-free DNA (ccfDNA) in blood from cancer patients represents a promising approach for minimally invasive, real-time monitoring of treatment response. Short stature homeobox 2 (SHOX2) and septin 9 (SEPT9) methylation was analyzed in N = 8865 malignant and N = 746 normal adjacent tissues across 33 different malignancies from The Cancer Genome Atlas. Furthermore, we performed quantitative SHOX2 and SEPT9 ccfDNA methylation analysis in plasma obtained before and consecutively during treatment from prospectively enrolled N = 115 patients with various advanced cancers. SHOX2 and/or SEPT9 hypermethylation in malignant tissues is present in various carcinomas, sarcoma, melanoma, brain tumors, mesothelioma, and hematopoietic malignancies. Among the prospectively enrolled cancer patients, 61% (70/115) of patients had a baseline-positive blood cumulative ccfDNA methylation score (CMS) and were eligible for response monitoring. Dynamic changes of CMS during treatment were strongly associated with treatment response. A CMS increase indicated response up to 80 days before conventional monitoring. SHOX2 and SEPT9 ccfDNA methylation represents a pan-cancer biomarker and has the potential to be a powerful tool for monitoring treatment response in patients with solid tumors and lymphomas. The early identification of nonresponders might allow for a timely change of treatment regimen.

  Copyright © 2020 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

2010s

• Validation of a Gene Expression Test for Mesothelioma Prognosis in Formalin-Fixed Paraffin-Embedded Tissues. A. De Rienzo, R.W. Cook, J. Wilkinson, et al. 2017;19(1):65-71. PubMed · Publisher · Free full text

  Abstract

  A molecular test performed using fresh-frozen tissue was proposed for use in the prognosis of patients with pleural mesothelioma. The accuracy of the test and its properties was assessed under Clinical Laboratory Improvement Amendments-approved guidelines using FFPE tissue from an independent multicenter patient cohort. Concordance studies were performed using matched frozen and FFPE mesothelioma samples. The prognostic value of the test was evaluated in an independent validation cohort of 73 mesothelioma patients who underwent surgical resection. FFPE-based classification demonstrated overall high concordance (83%) with the matched frozen specimens, on removal of cases with low confidence scores, showing sensitivity and specificity in predicting type B classification (poor outcome) of 43% and 98%, respectively. Concordance between research and clinical methods increased to 87% on removal of low confidence cases. Median survival times in the validation cohort were 18 and 7 months in type A and type B cases, respectively (P = 0.002). Multivariate classification adding pathologic staging information to the gene expression score resulted in significant stratification of risk groups. The median survival times were 52 and 14 months in the low-risk (class 1) and intermediate-risk (class 2) groups, respectively. The prognostic molecular test for mesothelioma can be performed on FFPE tissues to predict survival, and can provide an orthogonal tool, in combination with established pathologic parameters, for risk evaluation.

  Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

• Diagnostic potential of miR-126, miR-143, miR-145, and miR-652 in malignant pleural mesothelioma. M. Andersen, M. Grauslund, J. Ravn, et al. 2014;16(4):418-30. PubMed · Publisher

  Abstract

  Malignant pleural mesothelioma (MPM) is difficult to distinguish from reactive mesothelial proliferations (RMPs). It is uncertain whether miRNAs are useful biomarkers for differentiating MPM from RMPs. Thus, we screened with a quantitative RT-PCR (RT-qPCR)-based platform the expression of 742 miRNAs in formalin-fixed, paraffin-embedded, preoperative diagnostic biopsy samples, surgically resected MPM specimens previously treated with chemotherapy, and corresponding non-neoplastic pleura (NNP), from five patients. miR-126, miR-143, miR-145, and miR-652 were significantly down-regulated (≥twofold) in resected MPM and/or chemotherapy-naïve diagnostic tumor biopsy samples. The miRNA expression pattern was validated by RT-qPCR in a cohort of 40 independent MPMs. By performing binary logistic regression on the RT-qPCR data for the four miRNAs, the established four-miRNA classifier differentiated MPM from NNP with high sensitivity and specificity (area under the curve, 0.96; 95% CI, 0.92-1.00). The classifier's optimal logit(P) value of 0.62 separated NNP and MPM samples with a sensitivity of 0.95 (95% CI, 0.89-1.00), a specificity of 0.93 (95% CI, 0.87-0.99), and an overall accuracy of 0.94 (95% CI, 0.88-1.00). The level of miR-126 in MPM was inversely correlated with that of the known target, the large neutral amino acid transporter, small subunit 1 (r = -0.38; 95% CI, -0.63 to -0.06). Overall, these results indicate that these four miRNAs may be suitable biomarkers for distinguishing MPM from RMPs.

  Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

• A diagnostic assay based on microRNA expression accurately identifies malignant pleural mesothelioma. H. Benjamin, D. Lebanony, S. Rosenwald, et al. 2010;12(6):771-9. PubMed · Publisher · Free full text

  Abstract

  The definitive identification of malignant pleural mesothelioma (MPM) has significant clinical implications, yet other malignancies often involve the lung pleura, confounding the diagnosis of MPM. In the absence of accurate markers, MPM can be difficult to distinguish from peripheral lung adenocarcinoma and metastatic epithelial cancers. MicroRNA expression is tissue-specific and highly informative for identifying tumor origin. We identified microRNA biomarkers for the differential diagnosis of MPM and developed a standardized microRNA-based assay. Formalin-fixed, paraffin-embedded samples of 33 MPM and 210 carcinomas were used for assay development. Using microarrays, we identified microRNAs differentially expressed between MPM and various carcinomas. Hsa-miR-193-3p was overexpressed in MPM, while hsa-miR-200c and hsa-miR-192 were overexpressed in peripheral lung adenocarcinoma and carcinomas that frequently metastasize to lung pleura. We developed a standardized diagnostic assay based on the expression of these microRNAs. The assay reached a sensitivity of 100% and a specificity of 94% in a blinded validation set of 68 samples from the lung and pleura. This diagnostic assay can provide a useful tool in the differential diagnosis of MPM from other malignancies in the pleura.

2000s

• Severe chromosomal aberrations in pleural mesotheliomas with unusual mesodermal features. Comparative genomic hybridization evidence for a mesothelioma subgroup. M. Krismann, K.M. Müller, M. Jaworska, et al. 2000;2(4):209-16. PubMed · Publisher · Free full text

  Abstract

  Malignant mesotheliomas are tumors known for their extensive heterogeneity. Apart from the three classical patterns, predominantly epithelioid, sarcomatoid, and biphasic, some rare variants do exist. In some cases, one can find uncommon additional mesodermal tumor components. These tumors have previously been called "mesodermomas" and, like regular mesotheliomas, are usually associated with a previous asbestos exposure. We examined eight cases of mesodermomas by light microscopy, immunohistochemistry and comparative genomic hybridization (CGH). Besides biphasic and epithelioid areas, unusual epithelial, chondroid, osseous, or even angioblastic elements may be found to varying degrees. Immunohistochemical analysis shows similar staining results as with regular mesotheliomas. CGH reveals a high number of chromosomal imbalances (16.5 per case; range, 11-27). In 10 classical biphasic mesotheliomas that served as a control, defects of comparable number and severity could not be detected (8 per case; range, 2-16). The most frequent defects of mesodermomas (losses on 1p, 4pq, 9p, 13q, 14q, and gains on 1q and 15q), however, could also be found in mesotheliomas of the classical type. Thus, our results support the classification of the so-called mesodermomas as a separate tumor subgroup while maintaining the relationship to the classical mesotheliomas. Therefore, we propose to use the term mesodermoma for this subgroup.

Browse every journal in the library or the library by type of article, or return to medical research.