Browsing by Author "Curless, Kendra"

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    Detection of BRAF Mutations on Direct Smears of Thyroid Fine Needle Aspirates through Cell Transfer Technique
    (Oxford, 2015-04) Shi, Qiuying; Ibrahim, Ashley; Herbert, Kristi; Carvin, Marcia; Randolph, Melissa; Post, Kristin M.; Curless, Kendra; Chen, Shaoxiong; Cramer, Harvey M.; Cheng, Liang; Wu, Howard H.; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Objectives: To determine the utility of the cell transfer technique (CTT) for BRAF molecular testing on thyroid fine-needle aspiration (FNA) specimens. Methods: Polymerase chain reaction (PCR)–based BRAF molecular testing was performed on tissues obtained through CTT from both air-dried and ethanol-fixed direct smears of thyroid FNA specimens and then compared with the corresponding thyroidectomy formalin-fixed, paraffin-embedded (FFPE) tissues on 30 cases. Results: BRAF testing was successfully performed on 29 of 30 air-dried CTT, 27 of 30 ethanol-fixed CTT, and 27 of 30 FFPE tissues. The results exhibited 11, 13, and 13 BRAF mutations and 18, 14, and 14 wild types for the air-dried CTT, the ethanol-fixed CTT, and the FFPE tissues, respectively. The concordance rate was 96% between air-dried and ethanol-fixed CTT tissues, 88% between air-dried CTT and FFPE tissues, and 92% between ethanol-fixed CTT and FFPE tissues. Conclusions: PCR-based BRAF mutational testing can be reliably performed on the direct smears of the thyroid FNA specimens through the application of CTT.
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    Diagnostic Utility of IDH1/2 Mutations to Distinguish Dedifferentiated Chondrosarcoma from Undifferentiated Pleomorphic Sarcoma of Bone
    (Elsevier, 2017) Chen, Shaoxiong; Fritchie, Karen; Wei, Shi; Ali, Naser; Curless, Kendra; Shen, Tiansheng; Brini, Anna T.; Latif, Farida; Sumathi, Vaiyapuri; Siegal, Gene P.; Cheng, Liang; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Histologically it is nearly impossible to distinguish the dedifferentiated component of dedifferentiated chondrosarcoma from undifferentiated pleomorphic sarcoma of bone when the low-grade cartilaginous component is absent. Previous studies have revealed that isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are present in a significant number of cartilaginous tumors including the majority of conventional chondrosarcoma and dedifferentiated chondrosarcomas. These mutations have not been studied in undifferentiated pleomorphic sarcomas of bone. We sought to investigate whether an IDH1 or IDH2 mutation signature could be used as a clinically diagnostic marker for the distinction of dedifferentiated component of chondrosarcoma from undifferentiated pleomorphic sarcoma of bone. Sixty-eight bone tumor cases, including 31 conventional chondrosarcomas, 23 dedifferentiated chondrosarcomas, and 14 undifferentiated pleomorphic sarcomas of bone, were collected for IDH1/2 mutation analysis either using the Qiagen IDH1/2 RGQ PCR Kit or using whole exome sequencing. IDH1/2 mutations were detected in 87% (20/23) of dedifferentiated chondrosarcomas and 30% (6/20) of conventional chondrosarcomas. No mutations were detected in the IDH1/2 codon 132 or codon 172 among 14 UPS of bone. Identification of IDH1 or IDH2 mutations supports the diagnosis of dedifferentiated chondrosarcoma rather than undifferentiated pleomorphic sarcoma of bone while also providing some insight into the pathogenesis of these two lesions.
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    Mucinous intrahepatic cholangiocarcinoma: a distinct variant
    (Elsevier, 2018) Chi, Zhikai; Bhalla, Amarpreet; Saeed, Omer; Cheng, Liang; Curless, Kendra; Wang, Hanlin L.; Patil, Deepa T.; Lin, Jingmei; Pathology and Laboratory Medicine, School of Medicine
    Mucinous variant of intrahepatic cholangiocarcinoma (iCC) is rare, and its clinicopathological features and prognosis are far less clear. Six patients who had iCCs with more than 50% of mucinous component and 79 conventional iCCs were included in the study. The mean size of mucinous and conventional iCCs was 6.2 cm and 6.0 cm, respectively. The majority of patients (83%) with mucinous iCC presented at T3 stage or above, compared to 28% of the conventional group (p < 0.01). Three patients with mucinous iCC (50%) died within 1 year. The average survival time of patients with mucinous iCCs was significantly reduced compared to that of conventional group (9 months vs 2 years; P < .001). Immunohistochemistry was performed on 6 mucinous and 12 conventional iCCs with matched age, sex and stage, which revealed positive immunoreactivity in MUC1 (83% vs 58%), MUC2 (33% vs 17%), MUC5AC (100% vs 42%), MUC6 (50% vs 0), CK7 (83% vs 83%), CK20 (0 vs 17%), and CDX2 (17% vs 0) in mucinous and conventional iCCs, respectively. Molecular studies showed one mucinous iCC with KRAS G12C mutation and no BRAF or IDH1/2 mutations. Mucinous iCC is a unique variant that constitutes 7.2% of iCCs. It is more immunoreactive for MUC1, MUC2, MUC5AC and MUC6. Unlike adenocarcinomas of colorectal primary, mucinous iCCs are often CK7+/CK20-/CDX2- and microsatellite stable. Patients with mucinous iCC likely present at advanced stage upon diagnosis with shorter survival time compared to the conventional counterparts.
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    Utilization of Cell-Transfer Technique for Molecular Testing on H&E-stained Sections- A Viable Option for Small Biopsies that Lack Tumor Tissues in Paraffin Block
    (2016-12) Wu, Howard H.; Jovonovich, Stephen M.; Randolph, Melissa; Post, Kristin M.; Sen, Joyashree D.; Curless, Kendra; Cheng, Liang; Department of Pathology and Laboratory Medicine, School of Medicine
    Context.— In some instances the standard method of doing molecular testing from formalin-fixed, paraffin-embedded block is not possible because of limited tissue. Tumor cell–enriched cell-transfer technique has been proven useful for performing immunocytochemistry and molecular testing on cytologic smears. Objective.— To establish the cell-transfer technique as a viable option for isolating tumor cells from hematoxylin-eosin (H&E)–stained slides. Design.— Molecular testing was performed by using the cell-transfer technique on 97 archived H&E-stained slides from a variety of different tumors. Results were compared to the conventional method of molecular testing. Results.— Polymerase chain reaction–based molecular testing via the cell-transfer technique was successfully performed on 82 of 97 samples (85%). This included 39 of 47 cases for EGFR, 10 of 11 cases for BRAF, and 33 of 39 cases for KRAS mutations. Eighty-one of 82 cell-transfer technique samples (99%) showed agreement with previous standard method results, including 4 mutations and 35 wild-type alleles for EGFR, 4 mutations and 6 wild-type alleles for BRAF, and 11 mutations and 21 wild-type alleles for KRAS. There was only 1 discrepancy: a cell-transfer technique with a false-negative >KRAS result (wild type versus G12C). Conclusions.— Molecular testing performed on H&E-stained sections via cell-transfer technique is useful when tissue from cell blocks and small surgical biopsy samples is exhausted and the only available material for testing is on H&E-stained slides.