Single Nucleotide Polymorphism-Based Noninvasive Prenatal Testing: Experience in India.

INTRODUCTION: Noninvasive prenatal testing (NIPT) has revolutionized prenatal screening for chromosomal aneuploidies in some countries. Its implementation has been sporadic in developing countries. Given the genetic variation of the people in different countries, we evaluated the performance of the SNP-based NIPT in India . MATERIALS AND METHODS: The Panorama™ NIPT was performed in 516 pregnancies, which had tested intermediate-to-high risk on conventional first and second trimester screening. Results were confirmed either by invasive diagnostic testing or by clinical evaluation after birth. RESULTS: Of 511 samples analyzed, results were obtained in 499 (97.7%). Of these, 480 (98.2%) were low risk and 19 were high risk. A sensitivity of 100% was obtained for detection of trisomies 21, 18, 13 and sex chromosomal abnormalities. The specificity ranged from 99.3 to 100% for abnormalities tested. Taken together, the positive predictive value for trisomies 21, 18, 13 and monosomy X was 85.7%. The average fetal fraction was 8.2%, which is lower than the average observed elsewhere. CONCLUSION: This is the first report of detailed experience with NIPT in India and demonstrates comparable performance in all aspects of testing to the results elsewhere.

CD34 positive-microgranular variant of acute promyelocytic leukemia in a child.

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) in which abnormal promyelocytes predominate. APL is rare in children (approximately 10% of childhood AML) and is characterized by a higher incidence of hyperleukocytosis, an increased incidence of microgranular morphology, the presence of balanced t(15;17)(q22;q11.2-12) translocation, and more frequent occurrence of the PML-RARα isoforms bcr 2 and bcr 3 compared to adults. The cytomorphology of microgranular variant blasts is obviously different from AML M3 blasts; these cells have a nongranular or hypogranular cytoplasm or contain fine dust-like cytoplasmic azurophil granules that may not be apparent by light microscopy. This case report emphasizes the importance of a high index of suspicion for the diagnosis of APL, the hypogranular variant in particular. They are responsive to differentiation therapy with all trans-retinoic acid and complete remission in seen in >80% cases.

Her-2/neu overexpression due to polysomy 17 in breast cancer: molecular testing to guide therapeutic options.

BACKGROUND: Fluorescent in situ hybridization (FISH) equivocal results for Her-2/neu still pose a diagnostic dilemma in oncology practice. In this study, we evaluate if Her-2/neu mRNA expression is an alternative to FISH for detecting Her-2/neu positivity. PATIENTS AND METHODS: Archival paraffin blocks of 54 breast cancer patients were analyzed for Her-2/neu status using immunohistochemistry (IHC), FISH, and Her-2/neu gene expression using mRNA. RESULTS: There was a 100% positive agreement and 64.7% negative agreement of Her-2/neu mRNA expression with respect to the reference standard (FISH), with the kappa value for agreement being 0.36. mRNA levels correlated positively and strongly with FISH ratio and IHC positivity. For Her-2/neu mRNA expression, Her-2/neu copy number was a significant predictor indicating that mRNA expression is independent of polysomy status. CONCLUSIONS: Her-2/neu mRNA expression may help tide over ambiguity posed by polysomy and FISH equivocal samples.