Elizabeth Hyjek

University of Chicago, Chicago, Illinois, United States

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Publications (17)84.13 Total impact

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    ABSTRACT: Although patients with medullary thyroid cancer are known to present with paraneoplastic hormone production, this is much less common with papillary thyroid cancer.
    Clinica Chimica Acta 08/2014; 438. · 2.85 Impact Factor
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    ABSTRACT: Objective Kaposi sarcoma (KS) is a rare disease that presents as one of four distinct clinicopathologic subtypes, however it may present in populations outside those normally encountered. In such cases, it will be important to consider KS in the differential diagnosis, as it may mimic other neoplastic and non-neoplastic entities. Methods We describe two cases of KS, one in a patient not clinically fitting any of the four subtypes and the other in a patient with atypical presentation in HIV-associated disease. The first is an 81 year old African-American (AA) female with a history of KS of the leg, who presented with groin lymphadenopathy (LAD) and the second a 42 year old AA male with a known history of HIV infection, no skin lesions, and new axillary LAD. Results Fine needle aspiration of the groin and axillary lymph node, respectively, showed atypical spindle cells in a lymphoplasmacytic background. The spindle cells were positive for HHV-8 on the cell block and subsequent lymph node excision. In patients with HIV infection, in addition to reactive and lymphoproliferative processes, KS should be considered. In the former case, the demographic of an elderly AA woman without immunosuppression would not cause concern for systemic KS, but rather a metastatic tumor or lymphoma. Conclusion Cytology is a helpful tool in narrowing the differential diagnosis for spindle cell lesions. With a diagnosis of KS, clinicians would be able to query the clinical history for a possible etiology, such as HIV, and exclude the possibility of metastatic disease.
    Journal of the American Society of Cytopathology. 04/2014;
  • Leukemia & lymphoma 02/2014; · 2.61 Impact Factor
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    ABSTRACT: BACKGROUND: Recent studies have demonstrated that partial or complete loss of E-cadherin (EC) and nuclear accumulation of zeste homolog 2 (EZH2) are hallmarks of poorly differentiated pancreatic adenocarcinoma (PAC). Depletion of EZH2 sensitizes cancer cells to chemotherapy in vitro. The objective of this study was to determine EC and EZH2 expression by immunohistochemistry (IHC) in samples obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as potential biomarkers for treatment and disease prognosis. METHODS: Thirty-eight EUS-FNA samples from patients with a PAC diagnosis were analyzed by IHC for EC and EZH2 expression. Seven corresponding surgical resection specimens were included in the study. The intensity of EZH2 and EC expression in PAC and in normal gastrointestinal pick-ups (internal positive control) was scored by using a 4-tier grading system. RESULTS: EC demonstrated a focal, weak-to-moderate decrease in 24 PAC samples. Complete loss of EC expression was observed in the poorly differentiated areas represented by single tumor cells. The average staining intensity of EC in samples of poorly differentiated PAC was significantly lower than that of moderately differentiated PAC samples (P = .0005). EZH2 was variably positive in 31 of 38 PAC samples. The average staining intensity of EZH2 in moderately and poorly differentiated PACs did not differ significantly (P = .81). CONCLUSIONS: EC and EZH2 expression was determined reliably by IHC on paraffin sections of EUS-FNA cell block specimens. The current results were consistent with prior reports indicating a decrease or loss of EC expression in poorly differentiated PAC. However, EZH2 expression did not always correlate inversely with EC expression and was more heterogeneous. Cancer (Cancer Cytopathol) 2013. © 2013 American Cancer Society.
    Cancer Cytopathology 05/2013; · 4.43 Impact Factor
  • Journal of Histochemistry and Cytochemistry 04/2013; · 2.26 Impact Factor
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    ABSTRACT: Malignant cells may evade death from cytotoxic agents if they are in a dormant state. The host microenvironment plays important roles in cancer progression, but how niches might control cancer cell dormancy is little understood. Here we show that osteopontin (OPN), an extracellular matrix molecule secreted by osteoblasts, can function to anchor leukemic blasts in anatomic locations supporting tumor dormancy. We demonstrate that acute lymphoblastic leukemia (ALL) cells specifically adhere to OPN in vitro and secrete OPN when localized to the endosteal niche in vivo. Using intravital microscopy to image the calvarial bone marrow (BM) of xenografted mice, we show that OPN is highly expressed adjacent to dormant tumor cells within the marrow. Inhibition of the OPN signaling axis significantly increases the leukemic cell Ki-67 proliferative index and leads to a two-fold increase in tumor burden in treated mice. Moreover, utilizing cell cycle-dependent Ara-C chemotherapy to produce minimal residual disease (MRD) in leukemic mice, we show that OPN neutralization synergizes with Ara-C to reduce detectable BM MRD. Taken together, these data suggest that ALL interacts with extracellular OPN within the malignant BM, and that this interaction induces cell cycle exit in leukemic blasts, protecting them from cytotoxic chemotherapy.
    Blood 04/2013; · 9.78 Impact Factor
  • American Journal of Respiratory and Critical Care Medicine 03/2013; 187(6):663-5. · 11.04 Impact Factor
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    ABSTRACT: Esophageal cancer incidence is rising and has few treatment options. In studying receptor tyrosine kinases associated with esophageal cancers, we have identified EPHB4 to be robustly over expressed in cell lines and primary tumor tissues. In total, 94 squamous cell carcinoma (SCC), 82 adenocarcinoma, 25 dysplasia, 13 Barrett's esophagus and 25 adjacent or unrelated normal esophageal tissues were evaluated by IHC. EPHB4 expression was significantly higher in all the different histologic categories compared to adjacent normal tissues. In 13 esophageal cancer cell lines, three of the nine SCC cell lines and one of the four adenocarcinomas expressed very high levels of EPHB4. An increased gene copy number ranging from 4-20 copies was identified in a subset of the overexpressing patient samples and cell lines. We have developed a novel 4-NQO induced mouse model of esophageal cancer that recapitulates the EPHB4 expression in humans. A specific small molecule inhibitorof EPHB4 decreased cell viability in a time and dose dependent manner in three of the four cell lines tested. The small molecule inhibitor and an EPHB4 siRNA also decreased cell migration (12-40% closure in treated vs. 60-80% in untreated), with decreased phosphorylation of various tyrosyl containing proteins, EphB4 and its downstream target p125FAK. Finally, in a xenograft tumor model, an EPHB4 inhibitor abrogated tumor growth by approximately 60% compared to untreated control. EphB4 is robustly expressed and potentially serves as a novel biomarker for targeted therapy in esophageal cancers.
    Cancer Research 10/2012; · 9.28 Impact Factor
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    ABSTRACT: BACKGROUND: BRCA1--associated protein 1 (BAP1) is a tumor suppressor gene located on chromosome 3p21. Germline BAP1 mutations have been recently associated with an increased risk of malignant mesothelioma, atypical melanocytic tumors and other neoplasms. To answer the question if different germline BAP1 mutations may predispose to a single syndrome with a wide phenotypic range or to distinct syndromes, we investigated the presence of melanocytic tumors in two unrelated families (L and W) with germline BAP1 mutations and increased risk of malignant mesothelioma. METHODS: Suspicious cutaneous lesions were clinically and pathologically characterized and compared to those present in other families carrying BAP1 mutations. We then conducted a meta-analysis of all the studies reporting BAP1-mutated families to survey cancer risk related to the germline BAP1 mutation (means were compared using t-test and proportions were compared with Pearson Chi2 test or two-tailed Fisher's exact test). RESULTS: Melanocytic tumors: of the five members of the L family studied, four (80%) carried a germline BAP1 mutation (p.Gln684*) and also presented one or more atypical melanocytic tumors; of the seven members of W family studied, all carried a germline BAP1 mutation (p.Pro147fs*48) and four of them (57%) presented one or more atypical melanocytic tumors, that we propose to call "melanocytic BAP1-mutated atypical intradermal tumors" (MBAITs). Meta-analysis: 118 individuals from seven unrelated families were selected and divided into a BAP1-mutated cohort and a BAP1-non-mutated cohort. Malignant mesothelioma, uveal melanoma, cutaneous melanoma, and MBAITs prevalence was significantly higher in the BAP1-mutated cohort (p [LESS-THAN OR EQUAL TO] 0.001). CONCLUSIONS: Germline BAP1 mutations are associated with a novel cancer syndrome characterized by malignant mesothelioma, uveal melanoma, cutaneous melanoma and MBAITs, and possibly by other cancers. MBAITs provide physicians with a marker to identify individuals who may carry germline BAP1 mutations and thus are at high risk of developing associated cancers.
    Journal of Translational Medicine 08/2012; 10(1):179. · 3.46 Impact Factor
  • Leukemia & lymphoma 07/2012; · 2.61 Impact Factor
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    ABSTRACT: Diffuse large B-cell lymphomas in humans are associated with chromosomal rearrangements (∼40%) and/or mutations disrupting autoregulation (∼16%) involving the BCL6 gene. Studies of lymphoma development in humans and mouse models have indicated that lymphomagenesis evolves through the accumulation of multiple genetic alterations. Based on our prior studies, which indicated that carcinogen-induced DNA mutations enhance the incidence of lymphomas in our mouse model expressing a human BCL6 transgene, we hypothesized that mutated genes are likely to play an important cooperative role in BCL6-associated lymphoma development. We used retroviral insertional mutagenesis in an effort to identify which genes cooperate with BCL6 in lymphomagenesis in our BCL6 transgenic mice. We identified PIM1 as the most frequently recurring cooperating gene in our murine BCL6-associated lymphomas (T- and B-cell types), and we observed elevated levels of PIM1 mRNA and protein expression in these neoplasms. Further, immunohistochemical staining, which was performed in 20 randomly selected BCL6-positive human B- and T-cell lymphomas, revealed concurrent expression of BCL6 and PIM1 in these neoplasms. As PIM1 encodes a serine/threonine kinase, PIM1 kinase inhibition may be a promising therapy for BCL6/PIM1-positive human lymphomas.
    Proceedings of the National Academy of Sciences 03/2012; 109(15):5735-9. · 9.81 Impact Factor
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    ABSTRACT: Natural killer (NK) cells inhibit early stages of tumor formation, recurrence, and metastasis. Here, we show that NK cells can also eradicate large solid tumors. Eradication depended on the massive infiltration of proliferating NK cells due to interleukin 15 (IL-15) released and presented by the cancer cells in the tumor microenvironment. Infiltrating NK cells had the striking morphologic feature of being densely loaded with periodic acid-Schiff-positive, diastase-resistant granules, resembling uterine NK cells. Perforin-mediated killing by these densely granulated NK cells was essential for tumor eradication. Expression of the IL-15 receptor α on cancer cells was needed to efficiently induce granulated NK cells, and expression on host stromal cells was essential to prevent tumor relapse after near complete destruction. These results indicate that IL-15 released at the cancer site induces highly activated NK cells that lead to eradication of large solid tumors.
    Cancer Research 02/2012; 72(8):1964-74. · 9.28 Impact Factor
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    ABSTRACT: HOXA9 and MEIS1 have essential oncogenic roles in mixed lineage leukaemia (MLL)-rearranged leukaemia. Here we show that they are direct targets of miRNA-196b, a microRNA (miRNA) located adjacent to and co-expressed with HOXA9, in MLL-rearranged leukaemic cells. Forced expression of miR-196b significantly delays MLL-fusion-mediated leukemogenesis in primary bone marrow transplantation through suppressing Hoxa9/Meis1 expression. However, ectopic expression of miR-196b results in more aggressive leukaemic phenotypes and causes much faster leukemogenesis in secondary transplantation than MLL fusion alone, likely through the further repression of Fas expression, a proapoptotic gene downregulated in MLL-rearranged leukaemia. Overexpression of FAS significantly inhibits leukemogenesis and reverses miR-196b-mediated phenotypes. Targeting Hoxa9/Meis1 and Fas by miR-196b is probably also important for normal haematopoiesis. Thus, our results uncover a previously unappreciated miRNA-regulation mechanism by which a single miRNA may target both oncogenes and tumour suppressors, simultaneously, or, sequentially, in tumourigenesis and normal development per cell differentiation, indicating that miRNA regulation is much more complex than previously thought.
    Nature Communications 01/2012; 3:688. · 10.74 Impact Factor
  • Tatjana Antic, Elizabeth M Hyjek, Jerome B Taxy
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    ABSTRACT: Of patients with cryptorchidism, 5% have no palpable gonad. Physical examination or scrotal exploration demonstrates tissue nubbins or small nodules that constitute the vanishing testis syndrome. At the University of Chicago Hospitals (Chicago, IL; 2004-2008), 30 surgical pathology specimens from 29 patients with this clinical diagnosis underwent scrotal exploration. Histologic and immunohistochemical comparison was done with 7 fetal testes, 8 surgically removed nonneoplastic testes, and 2 cryptorchid testes. Routine histologic studies showed no seminiferous tubules in 18 cases (60%), fibrosis in all (100%), calcifications in 16 (53%), and hemosiderin deposits in 9 (30%). In 12 cases with seminiferous tubules (40%), there were Sertoli cells only. Scrotal exploration in such cases is clinically driven and results in the removal of any tissue present. Although published studies suggest the risk for future tumor development is low, possibly absent, the definitive removal of a testicle is established by an awareness of the histologic spectrum exhibited by testicular remnants.
    American Journal of Clinical Pathology 12/2011; 136(6):872-80. · 2.88 Impact Factor
  • Elizabeth Hyjek, James W Vardiman
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    ABSTRACT: The myelodysplastic/myeloproliferative neoplasms (MDS/MPN) include clonal myeloid neoplasms that overlap the MDS and MPN categories and at the time of initial diagnosis exhibit some clinical, laboratory, or morphologic features supporting the diagnosis of myelodysplastic syndrome (MDS) and at the same time show proliferative features in keeping with the diagnosis of a myeloproliferative neoplasm (MPN). Although the clinical, morphologic, and laboratory findings vary along a continuum from MDS to MPN, distinctive features are usually present that allow assignment of most of the cases to 1 of 3 distinct subtypes recognized by the 2008 World Health Organization (WHO) classification: chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia, BCR-ABL(-)(aCML, BCR-ABL1(-)), and juvenile myelomonocytic leukemia (JMML). The WHO classification also recognizes a provisional category of the MDS/MPN, unclassifiable (MDS/MPN, U), including the provisional entity of refractory anemia with ring sideroblasts and thrombocytosis (RARS-T). In the past 2 to 3 years since the publication of the WHO classification in 2008, dynamic progress in array technologies and next-generation amplicon deep sequencing has provided new insights into the molecular pathogenesis of MDS/MPN, especially CMML and JMML. In this review we will give an overview of these neoplasms and focus on adult MDS/MPN, especially CMML. We will give only brief updates for aCML and RARS-T; JMML will be discussed in a separate article.
    Seminars in Diagnostic Pathology 11/2011; 28(4):283-97. · 1.62 Impact Factor
  • James Vardiman, Elizabeth Hyjek
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    ABSTRACT: There is no single category in the fourth edition (2008) of the World Health Organization (WHO) classification of myeloid neoplasms that encompasses all of the diseases referred to by some authors as the myeloproliferative neoplasm (MPN) "variants." Instead, they are considered as distinct entities and are distributed among various subgroups of myeloid neoplasms in the classification scheme. These relatively uncommon neoplasms do not meet the criteria for any so-called "classical" MPN (chronic myelogenous leukemia, polycythemia vera, primary myelofibrosis, or essential thrombocythemia) and, although some exhibit myelodysplasia, none meets the criteria for any myelodysplastic syndrome (MDS). They are a diverse group of neoplasms ranging from fairly well-characterized disorders such as chronic myelomonocytic leukemia to rare and thus poorly characterized disorders such as chronic neutrophilic leukemia. Recently, however, there has been a surge of information regarding the genetic infrastructure of neoplastic cells in the MPN variants, allowing some to be molecularly defined. Nevertheless, in most cases, correlation of clinical, genetic, and morphologic findings is required for diagnosis and classification. The fourth edition of the WHO classification provides a framework to incorporate those neoplasms in which a genetic abnormality is a major defining criterion of the disease, such as those associated with eosinophilia and abnormalities of PDGFRA, PDGFRB, and FGFR1, as well as for those in which no specific genetic defect has yet been discovered and which remain clinically and pathologically defined. An understanding of the clinical, morphologic, and genetic features of the MPN variants will facilitate their diagnosis.
    Hematology 01/2011; 2011:250-6. · 1.49 Impact Factor

Publication Stats

104 Citations
84.13 Total Impact Points


  • 2014
    • University of Chicago
      • Department of Pathology
      Chicago, Illinois, United States
    • University of Toronto
      Toronto, Ontario, Canada
  • 2013
    • University of Illinois at Chicago
      • Department of Pathology (Chicago)
      Chicago, Illinois, United States