Huiying He

NYU Langone Medical Center, New York City, NY, United States

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Publications (9)26.78 Total impact

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    ABSTRACT: Epithelial-to-mesenchymal transition (EMT) describes a phenotypical change induced in epithelial cells that lose their cell-cell basement membrane contacts and their structural polarity to become spindle-shaped and morphologically similar to mesenchymal/myofibroblast cell. The abnormal induction of EMT has been demonstrated to contribute to cancer dissemination and progression. Renal cell carcinoma (RCC) with sarcomatoid differentiation (sarcomatoid RCC) represents a good example of EMT both morphologically and immunohistochemically. Early spindle cell changes can at times be identified in RCC and likely represent an early step toward EMT. Herein, we present a review of the current understanding of EMT in renal neoplasms including some known signaling regulation, the association of sarcomatoid differentiation in RCC with aggressive behavior and dismal prognosis, and EMT-related tumor biology in sarcomatoid RCC. A better perception of the EMT may contribute toward an improved understanding of the development of sarcomatoid RCC. In addition, a distinct signature for sarcomatoid RCC may have utility in the differential diagnosis for prognostic stratification as well as in identifying novel genes and pathway targets for therapeutic intervention.
    Advances in anatomic pathology 05/2014; 21(3):174-80. · 3.22 Impact Factor
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    ABSTRACT: Avian v-ets erythroblastosis virus E26 oncogene homolog (ERG) is highly sensitive and specific for endothelial neoplasms and specific for prostate carcinoma. We characterized a rabbit anti-ERG antibody as an immunohistochemical agent to detect ERG expression in various tumors using tissue microarrays with a wide array of epithelial and mesenchymal tumors. ERG was positive in 63 (38%) of 168 prostate carcinomas and negative in all other epithelial tumors. ERG was positive in all 125 vascular lesions. It was also positive in the sarcomatoid component of a high-grade urothelial carcinoma and 6 (40%) of 15 meningiomas. Twelve (80%) of 15 meningiomas were positive for Fli1, including all 6 ERG-positive cases. Positive immunostaining with this antibody is therefore highly specific for prostate carcinoma and vascular lesions, with a few caveats. ERG is rarely detected in nonvascular mesenchymal tumors with this antibody. Furthermore, about 40% of meningiomas are also positive for ERG immunohistochemically, probably because of cross-reactivity with Fli1.
    American Journal of Clinical Pathology 12/2012; 138(6):803-10. · 2.88 Impact Factor
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    ABSTRACT: Study Type - Diagnosis (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? High grade prostatic intraepithelial neoplasia is a pre-malignant lesion to prostate cancer and is associated with 20%-25% risk of prostate cancer in subsequent repeat biopsies. ERG is a highly prostate-cancer-specific marker. Expression of ERG is rare in isolated high grade prostatic intraepithelial neoplasia diagnosed in prostate biopsy and is not associated with cancer risk in subsequent repeat biopsies. OBJECTIVES: •  To evaluate how often ERG, a highly prostate-cancer-specific marker, is expressed in isolated high grade prostatic intraepithelial neoplasia (HGPIN) by immunohistochemistry. •  To study whether a positive ERG immunostain in HGPIN correlates with prostate cancer (PCa) detection in subsequent repeat biopsies. PATIENTS AND METHODS: •  Patients with initial HGPIN in biopsies and at least one follow-up prostate biopsy were included. •  Biopsies with HGPIN were immunostained for ERG. •  The ERG staining results were then correlated with the PCa risk in subsequent biopsies. RESULTS: •  The mean age of 94 patients was 63 years (range 48-78). A mean of 1.8 (range 1-5) repeat biopsy sessions were carried out at a mean interval of 27.4 months (range 1.5-140). The repeat biopsies showed PCa and non-cancer lesions (benign, HGPIN, atypical glands suspicious for cancer) in 36 patients (38%) and 58 patients (62%) respectively. •  ERG immunostain was positive in five (5.3%) biopsies with HGPIN, in which PCa was found in two (40%) subsequent biopsies. Of 89 biopsies with negative ERG staining, PCa was found in 34 (38%) repeat biopsies. The cancer detection rate was not different between ERG positive and negative cases (P= 0.299). CONCLUSIONS: •  This is the first study to investigate the ERG protein expression in prostate biopsy containing HGPIN only and its use to stratify the cancer risk associated with HGPIN. We found that ERG expression is distinctly uncommon in isolated HGPIN (5.3%). •  Positive ERG expression is not associated with increased cancer detection in subsequent repeat biopsies. The use of ERG immunostain in the evaluation and cancer risk stratification of HGPIN is of limited value.
    BJU International 10/2012; · 3.05 Impact Factor
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    ABSTRACT: Fine needle aspiration (FNA) diagnosis of salivary gland neoplasms with epithelial/myoepithelial cells but rare or no stroma is usually difficult. Our aim was to study the cytomorphology of this cohort of FNA cases and evaluate the clinical follow-up. The diagnostic terminology for this group of aspirates was 'favor an epithelial/myoepithelial neoplasm of the salivary gland'. The cytologic smears of 32 such cases were retrieved and showed cellular smears with bland-appearing or mildly atypical epithelial and myoepithelial cells without typical chondromyxoid stroma seen in pleomorphic adenoma (PA). Twenty of the 32 cases had histologic follow-up. Ten of these 20 cases were PAs, including 8 cellular PAs. Two cases were basal cell adenomas, 1 case myoepithelioma and 1 case benign adenoma, not otherwise specified. Among the 6 malignant tumors on surgical resections, there were 3 epithelial-myoepithelial carcinomas, 1 myoepithelial carcinoma, 1 basal cell adenocarcinoma and 1 adenoid cystic carcinoma. Although 14 of the 20 (70%) cases were benign neoplasms, a substantial amount of cases (30%) were malignant salivary gland neoplasms. The generic diagnostic terminology of 'epithelial/myoepithelial neoplasm of the salivary gland' and appropriate clinical follow-up are recommended for these cases.
    Acta cytologica 01/2012; 56(1):25-33. · 0.69 Impact Factor
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    ABSTRACT: Clear cell carcinoma of the female genital tract (CCCa) shares many histologic features with clear cell renal cell carcinoma (CCRCC) and translocation-associated renal cell carcinoma (TA-RCC), the latter in particular. When CCRCC or TA-RCC metastasizes to the female genital tract, or when patients have a history of both CCCa- and RCC-developed metastatic lesions, it is critical to distinguish the 3 lesions. Such a distinction is not always possible based on the morphology alone and often requires immunostains. We therefore investigated the utility of a panel of routinely used immunohistochemical markers including cytokeratin (CK) 7 and 20, CD10, α-methylacyl-CoA racemase, carbonic anhydrase IX (CA IX), TFE3, and WT-1 in the distinction of the 3 lesions on a tissue microarray of 12 CCCa, 5 TA-RCC, and 23 CCRCC cases. CK7 was positive in all CCCa cases, but only in 20% of TA-RCCs and 4.3% of CCRCCs. In contrast, CD10 was positive in all TA-RCCs and 91.3% of CCRCCs, but in only 7.5% of CCCa cases. TFE3 was positive in all TA-RCCs, but negative in all CCCa and CCRCC cases. CA IX was positive in 87% of CCRCCs, but in only 20% of TA-RCCs, and was negative in all CCCa cases. CK20, α-methylacyl-CoA racemase, and WT-1 were not contributory to the distinction. Although morphologically similar, CCCa can be reliably distinguished from TA-RCC and CCRCC. CCCa is mostly CK7/CD10/CA IX/TFE3, TA-RCC is usually CK7/CD10/CA IX/TFE3, whereas CCRCC is mostly CK7/CD10/CA IX/TFE3. To the best of our knowledge, this was the first study to directly compare the immunophenotypes of these 3 lesions.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 09/2011; 30(5):425-30. · 2.07 Impact Factor
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    ABSTRACT: TMPRSS2-ERG, the most common gene fusion in prostate cancer, is associated with expression of a truncated protein product of the oncogene ERG. A novel anti-ERG monoclonal antibody has been recently characterized. We investigated the correlation between ERG rearrangement assessed by fluorescence in situ hybridization (FISH) and ERG expression detected by immunohistochemistry in a large cohort of patients treated with radical prostatectomy for clinically localized prostate cancer. Thirteen tissue microarrays comprising 305 tumors and a subset of 112 samples of nonneoplastic prostatic tissue were assessed for ERG rearrangement status by FISH and for ERG expression by immunohistochemistry. Accuracy of ERG detection by immunohistochemistry in predicting ERG status as assessed by FISH (criterion standard) was calculated in terms of sensitivity, specificity, positive and negative predictive values. Of 305 tumor foci, 103 (34%) showed ERG rearrangement by FISH. ERG was detected by immunohistochemistry in 100 (33%) cases, 99 of which were FISH positive. ERG detection by immunohistochemistry demonstrated a sensitivity and specificity of 96% and 99%, respectively, with positive and negative predictive values of 99% and 98%, respectively. None of the 112 samples of nonneoplastic prostatic tissue was rearranged by FISH or showed any ERG expression. In conclusion, ERG detection by immunohistochemistry in prostate cancer was highly predictive of ERG rearrangement as assessed by FISH in a large cohort of prostatectomy patients. Given the high yield and the easier task of performing immunohistochemistry vs. FISH, ERG assessment by immunohistochemistry may be useful for characterizing ERG status in prostate cancer.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 07/2011; 459(4):441-7. · 2.68 Impact Factor
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    ABSTRACT: Diagnosis of limited cancer can be challenging in prostate needle biopsies, and immunohistochemistry is commonly used in such settings. Recently, TMPRSS2:ERG gene rearrangement was found to be highly specific for and detected in approximately 50% of prostate cancer. Positive immunohistochemical staining with a novel anti-ERG antibody highly correlated with TMPRSS2:ERG gene rearrangement status. We developed a double immunohistochemical staining containing both erythroblastosis virus E26 oncogen (ERG) and basal cell marker P63 antibodies and evaluated its use in the diagnosis of limited cancer in prostate needle biopsies. A total of 77 prostate needle biopsies containing cancer occupying <1 mm of the length of only 1 core of the entire biopsy set were stained with the double stain containing ERG and P63 antibodies. ERG positivity and its staining intensity in cancerous and other noncancerous lesions were evaluated. ERG expression was detected in 42% (32 of 77) of cases, with strong, moderate, and weak staining intensity in 72%, 16%, and 12% of cases. The staining was uniform in 84% of cases and heterogeneous in 16% of cases with different staining intensities in >10% of cancerous cells. High-grade prostatic intraepithelial neoplasia was present in 17 cases, and in 5 (29%) cases ERG was positive in high-grade prostatic intraepithelial neoplasia glands, which were all immediately adjacent to or intermingled with ERG-positive cancerous glands. In 4 additional cases, positive ERG staining was found in morphologically benign glands, which were also immediately adjacent to or intermingled with ERG-positive cancerous glands. All other benign lesions distant from cancerous glands, including simple and partial atrophy, were negative for ERG. P63 was negative in all cancerous glands and positive in noncancerous lesions. The P63/ERG double immunostain combines the high sensitivity of P63 and the high specificity of ERG and may be potentially useful in the work-up of difficult prostate biopsies. The high specificity of ERG for the presence of cancer may have important implications for prostate biopsy interpretation and needs to be further validated in larger prospective studies.
    The American journal of surgical pathology 07/2011; 35(7):1062-8. · 4.06 Impact Factor
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    ABSTRACT: A diagnosis of "atypical glands suspicious for cancer" (ATYP) in prostate needle biopsy is associated with a 40% to 50% risk of finding prostate carcinoma (PCa) in subsequent biopsies. Many studies have attempted to identify clinical, histologic, or molecular characteristics of ATYP that correlated with the risk of PCa in follow-up biopsies. TMPRSS2:ERG gene rearrangement is the most common chromosomal alteration and is highly specific for PCa. Recently, 2 studies reported that positive immunohistochemical (IHC) stains with an ERG antibody highly correlated with the TMPRSS2:ERG gene rearrangement status. We evaluated the use of this antibody as an IHC marker on prostate biopsies with an initial ATYP diagnosis to determine whether positive ERG IHC was associated with increased PCa detection in subsequent biopsies, which therefore might be useful for stratifying ATYP prostate biopsies. ERG IHC was performed on 103 biopsies with initial ATYP diagnosis. Positive ERG IHC staining was detected in 16 of the 103 cases (15.5%) of the ATYP prostate biopsies. Of these 16 ERG-positive cases, the atypical glands were positive for ERG in 9 cases. In the remaining 7 cases, positive ERG staining was found in glands other than ATYP glands, including high-grade prostatic intraepithelial neoplasia and morphologically benign glands. ERG IHC was negative in other benign prostate lesions, including simple atrophy, partial atrophy, proliferative inflammatory atrophy, basal cell hyperplasia, postatrophic hyperplasia, and squamous metaplasia. In subsequent follow-up biopsies, PCa was detected in 7 of the 16 (43.8%) ERG-positive cases and in 42 of the 87 (48.3%) ERG-negative cases (P=0.952 by χ test). In biopsies with ERG-positive ATYP glands, cancer was found in 5 of 9 (55.6%) cases in subsequent biopsies. This is the first study to investigate the use of ERG IHC in difficult prostate biopsies. ERG IHC was positive in a small percentage (15.5%) of the ATYP prostate biopsies, and positive ERG staining did not correlate with the increased cancer detection in subsequent prostate biopsies. Therefore, ERG IHC is not useful for stratifying ATYP prostate biopsies to identify patients who have increased risk for PCa in repeat biopsies. Furthermore, positive ERG staining is not entirely specific for PCa and can occasionally be found in high-grade prostatic intraepithelial neoplasia and benign glands that are not associated with PCa in prostate biopsies.
    The American journal of surgical pathology 03/2011; 35(4):608-14. · 4.06 Impact Factor
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    ABSTRACT: Recently several low-grade renal cell tumors, distinct from those recognized by the 2004 World Health Organization classification of renal tumors, have been described. These tumors had similar clinicopathologic features, being low-stage tumors with cystic, tubuloacinar, and/or papillary architecture. The tumor cells were low grade with variable amounts of clear cytoplasm that was positive for cytokeratin 7 (CK7), but negative for CD10. Genetic changes characteristic of clear cell or papillary renal cell carcinoma were not seen in these tumors. We investigated the morphologic, immunohistochemical, and genetic features of 36 additional tumors. Immunohistochemistry was carried out for CK7, carbonic anhydrase 9, α-methylacyl-CoA racemase, CD10, TFE-3, and desmin. Interphase fluorescence in situ hybridization was carried out with centromeric probes for chromosomes 3, 7, 17, and a subtelomeric probe for 3p25. Sequencing of von Hippel-Lindau gene and analysis of the methylation status of the promoter region was also carried out in 2 tumors. Thirty-six tumors from 33 patients (mean age: 60.4 , range: 26 to 88; 17 men and 16 women) were studied. Three patients had bilateral tumors and 1 patient had von Hippel-Lindau disease. Follow-up was available in 60% (20/33) of the patients for a mean of 27.4 (range 1 to 85) months. No patient had evidence of the disease after surgery except for the patient with von Hippel-Lindau disease, who was alive with stable disease in the contralateral kidney. All 36 tumors were small (mean size 2.4 cm; range 0.9 to 4.5 cm) and low stage (pT1). The majority was cystic and had prominent fibrous capsule and stroma. The tumors were composed of variable amount of cysts, papillae, tubules, acini, and solid nests. The most characteristic histologic features were branching tubules and acini and anastomosing clear cell ribbons with low-grade nuclei. All tumors were strongly positive for CK7 and variably positive for CA9, but largely negative for CD10, and negative for α-methylacyl-CoA racemase and TFE-3. All but 1 tumor had no gains of chromosomes 7 and 17 and deletion of 3p. Only 1 tumor had low copy number gains of chromosomes 7 and 17. VHL gene mutation and promoter methylation were negative in 2 tumors analyzed. We show that these tumors, which we term as "clear cell tubulopapillary renal cell carcinoma," constitute a unique subtype in the spectrum of renal epithelial neoplasia based on their characteristic morphologic and immunohistochemical features.
    The American journal of surgical pathology 09/2010; 34(11):1608-21. · 4.06 Impact Factor

Publication Stats

101 Citations
26.78 Total Impact Points

Institutions

  • 2012
    • NYU Langone Medical Center
      • Department of Pathology
      New York City, NY, United States
    • Peking University
      Peping, Beijing, China
  • 2011
    • Cleveland Clinic
      • Department of Anatomic Pathology
      Cleveland, OH, United States
  • 2010–2011
    • Cleveland Clinic Laboratories
      Cleveland, Ohio, United States