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Article ; Online: The Application of Guanidinium to Improve Biomolecule Quality in Fixed, Paraffin-embedded Tissue.

Chung, Joon-Yong / Kim, Kyungeun / Ylaya, Kris / Walker-Bawa, Katharine E / Perry, Candice / Star, Robert A / Hewitt, Stephen M

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society

2023 Volume 71, Issue 2, Page(s) 87–101

Abstract: Neutral buffered formalin (NBF) is the most common fixative in clinical applications. However, NBF damages proteins and nucleic acids, limiting the quality of proteomic and nucleic acid-based assays. Prior studies have demonstrated that BE70, a fixative ... ...

Abstract	Neutral buffered formalin (NBF) is the most common fixative in clinical applications. However, NBF damages proteins and nucleic acids, limiting the quality of proteomic and nucleic acid-based assays. Prior studies have demonstrated that BE70, a fixative of buffered 70% ethanol, has many benefits over NBF but the degradation of proteins and nucleic acids in archival paraffin blocks remain a challenge. Thus, we evaluated the addition of guanidinium salts to BE70 with the hypothesis that this may protect RNA and protein. Guanidinium salt supplemented BE70 (BE70G)-fixed tissue is comparable with that of BE70 via histology and immunohistochemistry. Western blot analysis also revealed that HSP70, AKT, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression signals in BE70G-fixed tissue were higher than those in BE70-fixed tissue. The quality of nucleic acids extracted from BE70G-fixed, paraffin-embedded tissue was also superior, and BE70G provides improved protein and RNA quality at shorter fixation times than its predecessors. The degradation of proteins, AKT and GAPDH, in archival tissue blocks is also decreased with the addition of guanidinium salt to BE70. In conclusion, BE70G fixative improves the quality of molecular analysis with more rapid fixation of tissue and enhanced long-term storage of paraffin blocks at room temperature for evaluation of protein epitopes.
MeSH term(s)	Fixatives ; Guanidine ; Proteomics ; Paraffin Embedding ; Paraffin ; Proto-Oncogene Proteins c-akt ; Formaldehyde ; RNA/analysis ; Nucleic Acids ; Tissue Fixation
Chemical Substances	Fixatives ; Guanidine (JU58VJ6Y3B) ; Paraffin (8002-74-2) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Formaldehyde (1HG84L3525) ; RNA (63231-63-0) ; Nucleic Acids
Language	English
Publishing date	2023-03-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	218208-7
ISSN	1551-5044 ; 0022-1554
ISSN (online)	1551-5044
ISSN	0022-1554
DOI	10.1369/00221554231159451
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Article ; Online: Quality Assessment of Proteins and RNA Following Storage in Archival Formalin-Fixed Paraffin-Embedded Human Breast Cancer Tissue Microarray Sections.

Kim, Kyungeun / Ylaya, Kris / Perry, Candice / Lee, Mi-Yeon / Kim, Jeong Won / Chung, Joon-Yong / Hewitt, Stephen M

Biopreservation and biobanking

2022 Volume 21, Issue 5, Page(s) 493–503

Abstract: Although the immunogenicity of formalin-fixed paraffin-embedded tissue sections can decrease during storage and transport, the exact mechanism of antigenic loss and how to prevent it are not clear. Herein, we investigated changes in the expression of ... ...

Abstract	Although the immunogenicity of formalin-fixed paraffin-embedded tissue sections can decrease during storage and transport, the exact mechanism of antigenic loss and how to prevent it are not clear. Herein, we investigated changes in the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), E-cadherin, and Ki-67 in human breast tissue microarray (TMA) tissue sections stored for up to 3 months in dry and wet conditions. The positive rates of ER and PR expression were minimally changed after 3 months of storage, but the Allred scores of ER and PR stored in humid conditions decreased remarkably in comparison to fresh-cut tissue. The HER-2 antigenicity and RNA integrity of breast TMA sections stored in dry conditions diminished gradually with storage time, whereas the immunoreactivity and RNA quality of HER-2 in humid conditions decreased sharply as storage length increased. The area and intensity of E-cadherin staining in tissue sections stored in dry conditions did not change significantly and were minimally changed after 3 months, respectively. In contrast, the area and intensity of E-cadherin staining in tissue sections stored in humid conditions decreased significantly as storage length increased. Finally, the Ki-67 labeling index of tissue sections stored for 3 months in dry (9% decrease) and wet (31.9% decrease) conditions was decreased in comparison to fresh sections. In conclusion, these results indicate that water is a crucial factor for protein and RNA degradation in stored tissue sections, and detailed guidelines are required in the clinic.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/genetics ; Immunohistochemistry ; Ki-67 Antigen/genetics ; Paraffin Embedding ; Formaldehyde ; Cadherins/genetics
Chemical Substances	Ki-67 Antigen ; Formaldehyde (1HG84L3525) ; Cadherins
Language	English
Publishing date	2022-10-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2593993-2
ISSN	1947-5543 ; 1947-5535
ISSN (online)	1947-5543
ISSN	1947-5535
DOI	10.1089/bio.2022.0090
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Article ; Online: Classification of Infant Vocalizations by Untrained Listeners.

Ramsdell-Hudock, Heather L / Warlaumont, Anne S / Foss, Lindsey E / Perry, Candice

Journal of speech, language, and hearing research : JSLHR

2019 Volume 62, Issue 9, Page(s) 3265–3275

Abstract: Purpose To better enable communication among researchers, clinicians, and caregivers, we aimed to assess how untrained listeners classify early infant vocalization types in comparison to terms currently used by researchers and clinicians. Method ... ...

Abstract	Purpose To better enable communication among researchers, clinicians, and caregivers, we aimed to assess how untrained listeners classify early infant vocalization types in comparison to terms currently used by researchers and clinicians. Method Listeners were caregivers with no prior formal education in speech and language development. A 1st group of listeners reported on clinician/researcher-classified vowel, squeal, growl, raspberry, whisper, laugh, and cry vocalizations obtained from archived video/audio recordings of 10 infants from 4 through 12 months of age. A list of commonly used terms was generated based on listener responses and the standard research terminology. A 2nd group of listeners was presented with the same vocalizations and asked to select terms from the list that they thought best described the sounds. Results Classifications of the vocalizations by listeners largely overlapped with published categorical descriptors and yielded additional insight into alternate terms commonly used. The biggest discrepancies were found for the vowel category. Conclusion Prior research has shown that caregivers are accurate in identifying canonical babbling, a major prelinguistic vocalization milestone occurring at about 6-7 months of age. This indicates that caregivers are also well attuned to even earlier emerging vocalization types. This supports the value of continuing basic and clinical research on the vocal types infants produce in the 1st months of life and on their potential diagnostic utility, and may also help improve communication between speech-language pathologists and families.
MeSH term(s)	Adult ; Child Language ; Female ; Hearing ; Humans ; Infant ; Male ; Phonation/physiology ; Speech/classification ; Speech/physiology ; Young Adult
Language	English
Publishing date	2019-08-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1364086-0
ISSN	1558-9102 ; 1092-4388
ISSN (online)	1558-9102
ISSN	1092-4388
DOI	10.1044/2019_JSLHR-S-18-0494
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Article ; Online: Comparison of warm vertical compaction protocols to obturate artificially created defects in the apical one-third.

Perry, Candice / Kulild, James C / Walker, Mary P

Journal of endodontics

2013 Volume 39, Issue 9, Page(s) 1176–1178

Abstract: Introduction: The purpose of this study was to evaluate the ability of 4 different warm vertical compaction protocols to obturate artificially created defects in the apical one-third of a root canal system by using a split-tooth model.: Methods: Four ...

Abstract	Introduction: The purpose of this study was to evaluate the ability of 4 different warm vertical compaction protocols to obturate artificially created defects in the apical one-third of a root canal system by using a split-tooth model. Methods: Four warm vertical protocols used (A) continuous down-pack and continuous backfill, (B) continuous down-pack and incremental backfill, (C) incremental down-pack and continuous backfill, and (D) incremental down-pack and incremental backfill. Three artificially created defects were placed 2, 3, and 4 mm from the apex of the split-tooth model. Before obturations, a fine-medium System B plugger was prefitted 4 mm from the working length. The root canal system was obturated according to each of the experimental protocols. Resultant obturations (N = 10/protocol) were separated from the model, and replicated defects were assessed by a blinded evaluator who used an ordinal scale (0-4) that was based on how much each defect was replicated by GP. Results: By using nonparametric analyses with Bonferroni adjustment (α = 0.01), with the apical 2-mm defect, protocol D demonstrated significantly (P ≤ .01) better defect replication as compared with protocols A, B, and C. For the apical 3-mm defect, protocols B and D were significantly better (P ≤ .01) than protocols A and C. However, there was no difference (P > .01) between protocols with apical 4-mm defect (100% replication). Conclusions: The incremental down-pack with incremental backfill appears better able to replicate the most apical defect, which suggests benefits of repeated heat application and packing force to manipulate the GP in the apical plug area.
MeSH term(s)	Dental Pulp Cavity/pathology ; Gutta-Percha/chemistry ; Hot Temperature ; Humans ; Materials Testing ; Microscopy/instrumentation ; Root Canal Filling Materials/chemistry ; Root Canal Obturation/instrumentation ; Root Canal Obturation/methods ; Root Canal Preparation/instrumentation ; Root Canal Preparation/methods ; Surface Properties ; Tooth Apex/pathology
Chemical Substances	Root Canal Filling Materials ; Gutta-Percha (9000-32-2)
Language	English
Publishing date	2013-09
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	752412-2
ISSN	1878-3554 ; 0099-2399
ISSN (online)	1878-3554
ISSN	0099-2399
DOI	10.1016/j.joen.2013.06.002
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Article ; Online: Tumor-associated macrophage, angiogenesis and lymphangiogenesis markers predict prognosis of non-small cell lung cancer patients.

Hwang, Ilseon / Kim, Jeong Won / Ylaya, Kris / Chung, Eun Joo / Kitano, Haruhisa / Perry, Candice / Hanaoka, Jun / Fukuoka, Junya / Chung, Joon-Yong / Hewitt, Stephen M

Journal of translational medicine

2020 Volume 18, Issue 1, Page(s) 443

Abstract: Background: The tumor microenvironment (TME) is a critical player in tumor progression, metastasis and therapy outcomes. Tumor-associated macrophages (TAMs) are a well-recognized core element of the TME and generally characterized as M2-like macrophages. ...

Abstract	Background: The tumor microenvironment (TME) is a critical player in tumor progression, metastasis and therapy outcomes. Tumor-associated macrophages (TAMs) are a well-recognized core element of the TME and generally characterized as M2-like macrophages. TAMs are believed to contribute to tumor progression, but the mechanism behind this remains unclear. We aimed to investigate the clinical, angiogenic, and lymphangiogenic significance of TAMs in non-small cell lung cancer (NSCLC). Methods: Utilizing combined immunohistochemistry and digital image analysis, we assessed CD68, CD163, VEGF-A, and VEGF-C expression in 349 patients with NSCLC. Subsequently, the potential association between M2 TAMs and angiogenic VEGF-A and/or lymphangiogenic VEGF-C was evaluated for its prognostic value. Furthermore, the effects of M2 TAMs on angiogenesis and lymphangiogenesis were explored via an in vitro co-culture system. Results: CD68 and CD163 expression were found to directly correlate with VEGF-A and/or VEGF-C expression (all p < 0.001). Furthermore, elevated M2 ratio (CD163+/CD68+) was significantly associated with poor overall survival (p = 0.023). Dual expression of M2 ratio Conclusions: This study suggests that TAMs are significantly associated with angiogenesis and lymphangiogenesis, contributing to the progression of NSCLC. Furthermore, elevated M2 ratio, similar to combined high M2 ratio and high VEGF-C expression, is a strong indicator of poor prognosis in patients with NSCLC, providing insight for future TAM-based immunotherapy strategies.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung ; Humans ; Lung Neoplasms ; Lymphangiogenesis ; Prognosis ; Tumor Microenvironment ; Tumor-Associated Macrophages
Language	English
Publishing date	2020-11-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ISSN	1479-5876
ISSN (online)	1479-5876
DOI	10.1186/s12967-020-02618-z
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Article ; Online: JAK inhibition in early-onset somatic, nonclonal STAT5B gain-of-function disease.

Eisenberg, Rachel / Gans, Melissa D / Leahy, Timothy Ronan / Gothe, Florian / Perry, Candice / Raffeld, Mark / Xi, Liqiang / Blackstone, Sarah / Ma, Chi / Hambleton, Sophie / Milner, Joshua D

The journal of allergy and clinical immunology. In practice

2020 Volume 9, Issue 2, Page(s) 1008–1010.e2

MeSH term(s)	Child, Preschool ; Gain of Function Mutation ; Humans ; Janus Kinases/antagonists & inhibitors ; Male ; STAT5 Transcription Factor/genetics ; STAT5 Transcription Factor/metabolism
Chemical Substances	STAT5 Transcription Factor ; STAT5B protein, human ; Janus Kinases (EC 2.7.10.2)
Language	English
Publishing date	2020-12-05
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2020.11.050
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Article: A multiplexed assay for quantifying immunomodulatory proteins supports correlative studies in immunotherapy clinical trials.

Whiteaker, Jeffrey R / Zhao, Lei / Schoenherr, Regine M / Huang, Dongqing / Lundeen, Rachel A / Voytovich, Ulianna / Kennedy, Jacob J / Ivey, Richard G / Lin, Chenwei / Murillo, Oscar D / Lorentzen, Travis D / Colantonio, Simona / Caceres, Tessa W / Roberts, Rhonda R / Knotts, Joseph G / Reading, Joshua J / Perry, Candice D / Richardson, Christopher W / Garcia-Buntley, Sandra S /

Bocik, William / Hewitt, Stephen M / Chowdhury, Shrabanti / Vandermeer, Jackie / Smith, Stephen D / Gopal, Ajay K / Ramchurren, Nirasha / Fling, Steven P / Wang, Pei / Paulovich, Amanda G

Frontiers in oncology

2023 Volume 13, Page(s) 1168710

Abstract: Introduction: Immunotherapy is an effective treatment for a subset of cancer patients, and expanding the benefits of immunotherapy to all cancer patients will require predictive biomarkers of response and immune-related adverse events (irAEs). To ... ...

Abstract	Introduction: Immunotherapy is an effective treatment for a subset of cancer patients, and expanding the benefits of immunotherapy to all cancer patients will require predictive biomarkers of response and immune-related adverse events (irAEs). To support correlative studies in immunotherapy clinical trials, we are developing highly validated assays for quantifying immunomodulatory proteins in human biospecimens. Methods: Here, we developed a panel of novel monoclonal antibodies and incorporated them into a novel, multiplexed, immuno-multiple reaction monitoring mass spectrometry (MRM-MS)-based proteomic assay targeting 49 proteotypic peptides representing 43 immunomodulatory proteins. Results and discussion: The multiplex assay was validated in human tissue and plasma matrices, where the linearity of quantification was >3 orders of magnitude with median interday CVs of 8.7% (tissue) and 10.1% (plasma). Proof-of-principle demonstration of the assay was conducted in plasma samples collected in clinical trials from lymphoma patients receiving an immune checkpoint inhibitor. We provide the assays and novel monoclonal antibodies as a publicly available resource for the biomedical community.
Language	English
Publishing date	2023-05-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1168710
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Article ; Online: A Buffered Alcohol-Based Fixative for Histomorphologic and Molecular Applications.

Perry, Candice / Chung, Joon-Yong / Ylaya, Kris / Choi, Chel Hun / Simpson, Amari / Matsumoto, Kaipo T / Smith, William A / Hewitt, Stephen M

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society

2016 Volume 64, Issue 7, Page(s) 425–440

Abstract: Formalin-fixed paraffin-embedded (FFPE) tissue is the predominant preparation for diagnostic histopathological evaluation and increasingly the biospecimen on which molecular diagnostics are performed. However, formalin is carcinogenic and results in ... ...

Abstract	Formalin-fixed paraffin-embedded (FFPE) tissue is the predominant preparation for diagnostic histopathological evaluation and increasingly the biospecimen on which molecular diagnostics are performed. However, formalin is carcinogenic and results in cross-linking of proteins and nicking and alterations of nucleic acids. Alternative fixatives, including 70% ethanol, improved biomolecular integrity; however, they have yet to replace neutral-buffered formalin (NBF). Herein, we describe the phosphate-buffered ethanol 70% (BE70) fixative. The histomorphology of BE70-fixed tissue is very similar to that of NBF; however, it is a non-cross-linking fixative and lacks the carcinogenic profile of formaldehyde-based fixatives. RNA isolated from tissue fixed in BE70 was of substantially higher quality and quantity than that was recovered from formalin-fixed tissue. Furthermore, the BE70 fixative showed excellent RNA and DNA integrity compared with that of NBF fixative based on real-time polymerase chain reaction analysis results. Immunohistochemical staining was similar for the antigen tested. In conclusion, BE70 is a non-cross-linking fixative that is superior to NBF and 70% ethanol with reference to biomolecule recovery and quality from paraffin-embedded tissue. Additional studies to compare the histomorphologic and immunohistochemical performance and utility in a clinical setting are required.
MeSH term(s)	Animals ; Buffers ; DNA/analysis ; Ethanol ; Fixatives ; Histological Techniques ; Kidney/chemistry ; Kidney/cytology ; Mice ; Phosphates ; Proteins/analysis ; RNA/analysis ; Tissue Fixation/methods
Chemical Substances	Buffers ; Fixatives ; Phosphates ; Proteins ; Ethanol (3K9958V90M) ; RNA (63231-63-0) ; DNA (9007-49-2)
Language	English
Publishing date	2016-05-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	218208-7
ISSN	1551-5044 ; 0022-1554
ISSN (online)	1551-5044
ISSN	0022-1554
DOI	10.1369/0022155416649579
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Article ; Online: Loss of ARID1A/BAF250a expression is linked to tumor progression and adverse prognosis in cervical cancer.

Cho, Hanbyoul / Kim, Jane Seon-Young / Chung, Hyunsoo / Perry, Candice / Lee, Heejeong / Kim, Jae-Hoon

Human pathology

2013 Volume 44, Issue 7, Page(s) 1365–1374

Abstract: The tumor suppressor gene ARID1A encodes BAF250a, a component of human SWI/SNF chromatin-remodeling complexes. Loss of BAF250a expression has recently been reported in several tumor types. To investigate the potential correlation between BAF250a and ... ...

Abstract	The tumor suppressor gene ARID1A encodes BAF250a, a component of human SWI/SNF chromatin-remodeling complexes. Loss of BAF250a expression has recently been reported in several tumor types. To investigate the potential correlation between BAF250a and various clinicopathologic parameters, we assessed the expression of BAF250a in archival tumor tissue specimens from 147 patients with cervical cancer and 191 with cervical intraepithelial neoplasia as well as 376 matched nonadjacent normal tissues by immunohistochemical staining. Messenger RNA expression level for BAF250a was decreased in cervical cancer cell lines (P = .013) and tissues (P = .010), when compared with normal cervical epithelial tissue using SYBR Green real-time polymerase chain reaction. BAF250a was also detected in nuclear fractions of HeLa cells and in nuclei of cervical cancer tissue samples by Western blotting and immunohistochemistry, respectively. BAF250a expression gradually decreased in transitioning from normal to cervical carcinoma (P < .001), and this loss of expression was significantly associated with tumor stage (P = .005), tumor grade (P = .029), tumor size (P = .003), and lymph node metastasis (P = .020). In multivariate analysis, overall survival in cervical cancer was significantly reduced in cases with BAF250a loss (hazard ratio, 2.78 [1.01-7.63]; P = .047). Our findings suggest a potential role for BAF250a in providing valuable prognostic information to clinicians for risk assessment in cervical cancer.
MeSH term(s)	Adenocarcinoma/genetics ; Adenocarcinoma/metabolism ; Adenocarcinoma/mortality ; Adenocarcinoma/secondary ; Adult ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Cervical Intraepithelial Neoplasia/genetics ; Cervical Intraepithelial Neoplasia/metabolism ; Cervical Intraepithelial Neoplasia/mortality ; Cervical Intraepithelial Neoplasia/pathology ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; HeLa Cells ; Humans ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Survival Rate ; Tissue Array Analysis ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Uterine Cervical Neoplasms/genetics ; Uterine Cervical Neoplasms/metabolism ; Uterine Cervical Neoplasms/mortality ; Uterine Cervical Neoplasms/pathology
Chemical Substances	ARID1A protein, human ; Biomarkers, Tumor ; Nuclear Proteins ; Transcription Factors
Language	English
Publishing date	2013-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207657-3
ISSN	1532-8392 ; 0046-8177
ISSN (online)	1532-8392
ISSN	0046-8177
DOI	10.1016/j.humpath.2012.11.007
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Article ; Online: Assessment of a panel of tumor markers for the differential diagnosis of benign and malignant effusions by well-based reverse phase protein array.

Braunschweig, Till / Chung, Joon-Yong / Choi, Chel Hun / Cho, Hanbyoul / Chen, Qing-Rong / Xie, Ran / Perry, Candice / Khan, Javed / Hewitt, Stephen M

Diagnostic pathology

2015 Volume 10, Page(s) 53

Abstract: Background: The differential diagnosis of benign and malignant effusion is often hampered by low cell content or insufficiently preserved tumor cells. In this study, we evaluated the combined diagnostic value of six tumor markers measured by well-based ... ...

Abstract	Background: The differential diagnosis of benign and malignant effusion is often hampered by low cell content or insufficiently preserved tumor cells. In this study, we evaluated the combined diagnostic value of six tumor markers measured by well-based reverse-phase protein array (RPPA) for diagnosis of malignant effusion. Methods: A total of 114 patients (46 with malignant effusions, 32 with probable malignant effusions, and 36 with benign effusions) were enrolled. Expressional levels of MUC1, EMA, Pan-CK, HSP90, TGF-β and CA125 were determined by well-based RPPA. Results: Median relative expression of MUC1, Pan-CK and EMA were significantly higher in malignant effusion than those in probable malignant or benign (p < 0.001, p = 0.003, p < 0.001, respectively), whereas the level of TGF-β in malignant effusions were significantly lower than that in the other groups (p = 0.005). For predicting malignancy, EMA presented the best areas under the curve of 0.728 followed by MUC1 of 0.701. The sensitivity of 52.0% for MUC1 and 48.0% for EMA were not better than cytology. However, sensitivity, negative predictive value, and accuracy of the tumor marker panel were better than cytology by 14.7%, 7.5%, and 6.1%, respectively. Conclusions: Tumor marker panel measured by well-based RPPA showed values in the differential diagnosis between benign and malignant effusions. Further large scale studies need to be performed to evaluate the utility of this panel of markers. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1433424467160224.
MeSH term(s)	Area Under Curve ; Biomarkers, Tumor/analysis ; Cluster Analysis ; Diagnosis, Differential ; Female ; Humans ; Male ; Pleural Effusion/diagnosis ; Pleural Effusion/etiology ; Pleural Effusion/metabolism ; Pleural Effusion, Malignant/chemistry ; Pleural Effusion, Malignant/diagnosis ; Pleural Effusion, Malignant/etiology ; Predictive Value of Tests ; Protein Array Analysis ; ROC Curve
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2015-05-29
Publishing country	England
Document type	Comparative Study ; Evaluation Studies ; Journal Article ; Research Support, N.I.H., Intramural
ISSN	1746-1596
ISSN (online)	1746-1596
DOI	10.1186/s13000-015-0290-4
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