Publications by authors named "Chaohui Lisa Zhao"

7 Publications

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Pathological findings in the postmortem liver of patients with coronavirus disease 2019 (COVID-19).

Hum Pathol 2021 03 8;109:59-68. Epub 2020 Dec 8.

NYU Long Island School of Medicine, NYU Langone Hospital - Long Island, Department of Pathology, 11501, USA. Electronic address:

Although coronavirus disease 2019 (COVID-19) is transmitted via respiratory droplets, there are multiple gastrointestinal and hepatic manifestations of the disease, including abnormal liver-associated enzymes. However, there are not many published articles on the pathological findings in the liver of patients with COVID-19. We collected the clinical data from 17 autopsy cases of patients with COVID-19 including age, sex, Body mass index (BMI), liver function test (alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), direct bilirubin, and total bilirubin), D-dimer, and anticoagulation treatment. We examined histopathologic findings in postmortem hepatic tissue, immunohistochemical (IHC) staining with antibody against COVID-19 spike protein, CD68 and CD61, and electron microscopy. We counted the number of megakaryocytes in liver sections from these COVID-19-positive cases. Abnormal liver-associated enzymes were observed in 12 of 17 cases of COVID-19 infection. With the exception of three cases that had not been tested for D-dimer, all 14 patients' D-dimer levels were increased, including the cases that received varied doses of anticoagulation treatment. Microscopically, the major findings were widespread platelet-fibrin microthrombi, steatosis, histiocytic hyperplasia in the portal tract, mild lobular inflammation, ischemic-type hepatic necrosis, and zone 3 hemorrhage. Rare megakaryocytes were found in sinusoids. COVID-19 IHC demonstrates positive staining of the histiocytes in the portal tract. Under electron microscopy, histiocyte proliferation is present in the portal tract containing lipid droplets, lysosomes, dilated ribosomal endoplasmic reticulum, microvesicular bodies, and coronavirus. The characteristic findings in the liver of patients with COVID-19 include numerous amounts of platelet-fibrin microthrombi, as well as various degrees of steatosis and histiocytic hyperplasia in the portal tract. Possible mechanisms are also discussed.
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http://dx.doi.org/10.1016/j.humpath.2020.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722493PMC
March 2021

Lipocalin-type prostaglandin D synthase deletion induces dyslipidemia and non-alcoholic fatty liver disease.

Prostaglandins Other Lipid Mediat 2020 08 4;149:106429. Epub 2020 Mar 4.

Department of Biomedical Research, NYU Winthrop Hospital, Mineola, NY 11501, United States. Electronic address:

Non-alcoholic fatty liver disease (NAFLD) is an emerging risk factor for type 2 diabetes mellitus, cardiovascular disease, and all-cause mortality. Previously, we demonstrated that lipocalin-type prostaglandin D synthase (L-PGDS) knockout mice show increased glucose intolerance and accelerated atherosclerosis. In the present study, we investigated the role of L-PGDS in mediating NAFLD utilizing L-PGDS knockout (KO) and control C57BL/6 mice fed either low fat (LFD) or high fat diet (HFD) for 14 weeks. Our present study demonstrates that L-PGDS KO mice remain slightly lighter in weight compared to control mice, yet develop NAFLD faster and eventually progress to the more severe non-alcoholic steatohepatitis (NASH). We found increased lipid accumulation in the liver of KO mice over time on both diets, as compared to control mice. The L-PGDS KO mice showed elevated fasting glucose and insulin levels and developed insulin resistance on both LFD and HFD. Lipogenesis marker proteins such as SREBP-1c and LXRα were increased in L-PGDS KO mice after 14 weeks on both diets, when compared to control mice. We replicated our in vivo findings in vitro using HepG2 cells treated with a combination of free fatty acids (oleic and palmitic acid) and exposure to a L-PGDS inhibitor and prostaglandin D receptor (DP1) antagonists. We conclude that the absence or inhibition of L-PGDS results in dyslipidemia, altered expression of lipogenesis genes and the acceleration of NAFLD to NASH, independent of diet and obesity. We propose L-PGDS KO mice as a useful model to explore the pathogenesis of NAFLD and NASH, and L-PGDS as a potential therapeutic target for treatment.
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http://dx.doi.org/10.1016/j.prostaglandins.2020.106429DOI Listing
August 2020

Stromal ColXα1 expression correlates with tumor-infiltrating lymphocytes and predicts adjuvant therapy outcome in ER-positive/HER2-positive breast cancer.

BMC Cancer 2019 Nov 1;19(1):1036. Epub 2019 Nov 1.

Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, 593 Eddy St, APC 12, Providence, RI, 02903, USA.

Background: The breast cancer microenvironment contributes to tumor progression and response to chemotherapy. Previously, we reported that increased stromal Type X collagen α1 (ColXα1) and low TILs correlated with poor pathologic response to neoadjuvant therapy in estrogen receptor and HER2-positive (ER+/HER2+) breast cancer. Here, we investigate the relationship of ColXα1 and long-term outcome of ER+/HER2+ breast cancer patients in an adjuvant setting.

Methods: A total of 164 cases with at least 5-year follow-up were included. Immunohistochemistry for ColXα1 was performed on whole tumor sections. Associations between ColXα1expression, clinical pathological features, and outcomes were analyzed.

Results: ColXα1 expression was directly proportional to the amount of tumor associated stroma (p = 0.024) and inversely proportional to TILs. Increased ColXα1 was significantly associated with shorter disease free survival and overall survival by univariate analysis. In multivariate analysis, OS was lower in ColXα1 expressing (HR = 2.1; 95% CI = 1.2-3.9) tumors of older patients (> = 58 years) (HR = 5.3; 95% CI = 1.7-17) with higher stage (HR = 2.6; 95% CI = 1.3-5.2). Similarly, DFS was lower in ColXα1 expressing (HR = 1.8; 95% CI = 1.6-5.7) tumors of older patients (HR = 3.2; 95% CI = 1.3-7.8) with higher stage (HR = 2.7; 95% CI = 1.6-5.7) and low TILs. In low PR+ tumors, higher ColXα1 expression was associated with poorer prognosis.

Conclusion: ColXα1 expression is associated with poor disease free survival and overall survival in ER+/HER2+ breast cancer. This study provides further support for the prognostic utility of ColXα1 as a breast cancer associated stromal factor that predicts response to chemotherapy.
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http://dx.doi.org/10.1186/s12885-019-6134-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825361PMC
November 2019

Temporal small arterial inflammation is common in patients with giant cell arteritis.

Hum Pathol 2018 11 25;81:65-70. Epub 2018 Jun 25.

Department of Pathology and Laboratory Medicine, Rhode Island Hospital/The Miriam Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.

Giant cell arteritis (GCA) primarily involves medium-to-large arteries. Small-vessel inflammation is a recognized phenomenon occurring in association with GCA. However, its significance is poorly elucidated. Histologic sections and medical records of105 temporal artery specimens were retrospectively reviewed between 2008 and 2017 to examine associated clinical manifestations and laboratory data including antinuclear antibody and p-antineutrophilic cytoplasmic antibody titers. Immunohistochemical staining for CD4 and CD8 was performed in select cases to assess the nature of the inflammatory response. Seventy-eight patients meeting the diagnostic criteria of temporal arteritis were included in the analysis. Twenty-eight specimens demonstrated temporal arteritis with small arterial inflammation (SAI), and 50 specimens showed temporal arteritis without SAI. Eight (28.6%) of 28 patients with SAI presented with jaw claudication, whereas 5 (17.9%) were febrile at presentation. In contrast, in 50 patients without SAI, jaw claudication and fever were seen in 11 and 2 cases, respectively (P = .01 and P = .0047, respectively). No statistically significant difference was noted between other symptoms and laboratory indices between the 2 groups. Elevated p-antineutrophilic cytoplasmic antibody titers in GCA may be associated with concomitant polymyalgia rheumatica or treatment-resistant disease. We also identified a higher count of CD4 and CD8 T cells in SAI cases, although the ratio of CD4/CD8 T lymphocytes was within normal limits. In conclusion, simultaneous involvement of arterioles and medium- to large-sized arteries is common in GCA and may be associated with treatment-refractory disease. Documentation of small arterial involvement in GCA will help the clinicians to manage the disease more effectively.
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http://dx.doi.org/10.1016/j.humpath.2018.06.020DOI Listing
November 2018

Alanine-glyoxylate aminotransferase 1 (AGXT1) is a novel marker for hepatocellular carcinomas.

Hum Pathol 2018 10 5;80:76-81. Epub 2018 Jun 5.

Department of Pathology and Laboratory Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02903. Electronic address:

Arginase-1 has been demonstrated as a marker for hepatocellular carcinoma (HCC) with higher sensitivity and specificity than HepPar-1 and glypican-3. However, its sensitivity is diminished in moderately and poorly differentiated HCCs. In the current study, we evaluated the utility of AGXT1 as a diagnostic marker. Immunostains for AGXT1 and arginase-1 were performed in tissue microarrays of 139 HCCs and 374 gastrointestinal and nongastrointestinal carcinomas. AGXT1 exhibited granular cytoplasmic immunoreactivity in contrast to the diffuse cytoplasmic staining characteristic of arginase-1 in nonneoplastic and neoplastic hepatocytes. Sensitivities of AGXT1 for all HCCs were 90.0% compared to 87.8% for arginase-1. A small number of tumors expressed only 1 of the 2 markers. Sensitivity increased to 92.1% when the presence of either marker was considered positive. Excepting 5 cases of cholangiocarcinoma, both AGXT1 and arginase-1 were negative in all non-HCC tumors with specificities of 98.7%. Our data support the consideration of AGXT1 as a novel hepatocellular marker with equally high specificity and slightly higher sensitivity as compared to arginase-1. AGXT1 may aid in diagnostic workup especially in conjunction with arginase-1 for HCCs that may otherwise defy conventional immunostaining patterns.
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http://dx.doi.org/10.1016/j.humpath.2018.05.025DOI Listing
October 2018

TGR5 expression in normal kidney and renal neoplasms.

Diagn Pathol 2018 Apr 2;13(1):22. Epub 2018 Apr 2.

Department of Pathology, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, 593 Eddy Street, APC 12, Providence, RI, 02903, USA.

Background: The G protein-coupled bile acid receptor (TGR5) is a cell surface receptor which induces the production of intracellular cAMP and promotes epithelial-mesenchymal transition in gastric cancer cell lines. TGR5 is found in a wide variety of tissues including the kidney. However, the patterns of TGR5 expression have not been well characterized in physiologic kidney or renal neoplasms. We explore the expression of TGR5 in benign renal tissue and renal neoplasms and assess its utility as a diagnostic marker.

Methods: Sixty-one renal cortical neoplasms from 2000 to 2014 were retrieved. TGR5 protein expression was examined by immunohistochemistry. TGR5 mRNA was also measured by real-time PCR.

Results: In normal renal tissue, TGR5 was strongly positive in collecting ducts, distal convoluted tubules and thin loop of Henle. Proximal convoluted tubules showed absent or focal weak staining. In clear cell renal cell carcinomas (RCCs), 25 of 27 cases (92%) were negative for TGR5 (p < 0.001). TGR5 mRNA was also significantly decreased in clear cell RCCs, suggesting that decreased TGR5 protein expression may be attributable to the downregulation of TGR5 mRNA in these tumors. All 11 papillary RCCs expressed TGR5 with 45% (5/11) exhibiting moderate to strong staining. All chromophobe RCCs and oncocytomas were positive for TGR5 with weak to moderate staining. TGR5 mRNA expression in these tumors was similar to normal kidney. All urothelial carcinomas of the renal pelvis strongly expressed TGR5 including a poorly differentiated urothelial carcinoma with sarcomatoid features.

Conclusion: TGR5 is strongly expressed in collecting ducts, distal convoluted tubules and thin loop of Henle. TGR5 protein and mRNA expression were notably decreased in clear cell RCCs and may be helpful in differentiating these tumors from other RCCs.
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http://dx.doi.org/10.1186/s13000-018-0700-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880016PMC
April 2018

T-complex-associated-testis-expressed 3 (TCTE3) is a novel marker for pancreatobiliary carcinomas.

Hum Pathol 2017 12 24;70:62-69. Epub 2017 Oct 24.

Department of Pathology and Laboratory Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02903. Electronic address:

Several markers of pancreatobiliary lineage have been described in the literature. However, none have demonstrated sufficient specificity and sensitivity to warrant diagnostic use. We evaluated the utility of T-complex-associated-testis-expressed 3 (TCTE3) as a pancreatobiliary marker. A set of 247 adenocarcinomas from the gastrointestinal (GI) tract was identified including 18 from the gastroesophageal junction (GEJ), 29 stomach, 17 ampullary, 62 pancreatic, and 16 common bile duct and gallbladder (CBD/GB), 13 non-ampullary small intestine, 32 colon, and 24 rectum. The remainder consisted of 16 cholangiocarcinomas and 20 hepatocellular carcinomas (HCC). Additionally, 163 adenocarcinomas from the breast, gynecologic tract, prostate, urothelium, kidney, and lung were stained for comparison. Immunohistochemistry for TCTE3 and other gastrointestinal markers was performed. Positive expression of TCTE3 was characterized by a strong, well-defined membranous pattern with or without weak cytoplasmic staining. Expression was identified in the normal epithelial cells of pancreatobiliary tree, but staining was absent in normal epithelial cells of esophagus, stomach, and intestine. Hepatocytes, pancreatic acini and islets and other non-epithelial cells were also negative for staining. TCTE3 was expressed in 93.5% of pancreatic ductal adenocarcinomas, 37.5% of CBD/GB adenocarcinomas, 50% of cholangiocarcinomas, 76.4% of ampullary adenocarcinomas, and 33.3% of GEJ adenocarcinomas. Only 3.5% of the gastric, 7.7% of non-ampullary small intestinal and 6.25% of colonic tumors exhibited positive staining. Expression was absent in rectal carcinomas and HCCs. These results suggest that TCTE3 is a useful marker of pancreatobiliary differentiation and may aid in distinguishing these tumors from gastric and intestinal primary tumors.
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http://dx.doi.org/10.1016/j.humpath.2017.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757622PMC
December 2017