scholarly journals Deep Learning Predicts EBV Status in Gastric Cancer Based on Spatial Patterns of Lymphocyte Infiltration

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6002
Author(s):  
Baoyi Zhang ◽  
Kevin Yao ◽  
Min Xu ◽  
Jia Wu ◽  
Chao Cheng
Keyword(s):  
Gastric Cancer ◽  
Deep Learning ◽  
In Situ Hybridization ◽  
Spatial Information ◽  
Immune Cell ◽  
Immune Infiltration ◽  
Ebv Infection ◽  
Significant Difference ◽  
Interpretable Models

EBV infection occurs in around 10% of gastric cancer cases and represents a distinct subtype, characterized by a unique mutation profile, hypermethylation, and overexpression of PD-L1. Moreover, EBV positive gastric cancer tends to have higher immune infiltration and a better prognosis. EBV infection status in gastric cancer is most commonly determined using PCR and in situ hybridization, but such a method requires good nucleic acid preservation. Detection of EBV status with histopathology images may complement PCR and in situ hybridization as a first step of EBV infection assessment. Here, we developed a deep learning-based algorithm to directly predict EBV infection in gastric cancer from H&E stained histopathology slides. Our model can not only predict EBV infection in gastric cancers from tumor regions but also from normal regions with potential changes induced by adjacent EBV+ regions within each H&E slide. Furthermore, in cohorts with zero EBV abundances, a significant difference of immune infiltration between high and low EBV score samples was observed, consistent with the immune infiltration difference observed between EBV positive and negative samples. Therefore, we hypothesized that our model’s prediction of EBV infection is partially driven by the spatial information of immune cell composition, which was supported by mostly positive local correlations between the EBV score and immune infiltration in both tumor and normal regions across all H&E slides. Finally, EBV scores calculated from our model were found to be significantly associated with prognosis. This framework can be readily applied to develop interpretable models for prediction of virus infection across cancers.

AMPLIFICATION AND OVEREXPRESSION OF HER2/NEU IN GASTRIC CANCER ASSESSED BY FLUORESCENCE IN SITU HYBRIDIZATION AND IMMUNOHISTOCHEMISTRY

2015 ◽  
pp. 22-31
Author(s):  
Van Huy Tran ◽  
Thi Minh Thi Ha ◽  
Viet Nho Le ◽  
Cong Thuan Dang ◽  
Trung Nghia Van ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Cancer Patients ◽  
Gene Amplification ◽  
Clinicopathologic Characteristics ◽  
Significant Difference ◽  
Her 2 ◽  
Gastric Cancer Patients

Background: HER2/neu is a predictive biomarker for treatment of gastric cancer using trastuzumab in combination with chemotherapy. This study aimed to: (1) assess the amplification and the overexpression of HER2/neu using fluorescence in situ hybridization (FISH) and immunohistochemistry in gastric cancer; (2) survey the association between HER2/neu and clinicopathologic characteristics of gastric cancer. Patients and methods: one hundred and sixty gastric cancer patients were assessed HER2/neu overexpression by IHC using Ventana anti-HER-2/neu (4B5) kit and were assessed HER2/neu gene amplification by FISH using PathVysionTM HER-2 DNA Probe kit with biopsy specimens. Results: HER2/neu protein expression rates of IHC 0, 1+, 2+ and 3+ were 70%, 10.6%, 10.6% and 8.8%, respectively. HER2/neu gene amplification was identified in gastric cancer from 21 out of 160 (13.1%) patients. The concordance between IHC and FISH was 90.0%. The HER2/neu-positive rate assessed by both techniques was 13.1%. There was a significant difference in HER2/neu-positivity between cardia gastric cancer and non-cardia gastric cancer (36.4% vs 11.4%, p = 0.040); between intestinal type and diffuse type (20.7% vs 5.9%, p = 0.010); between well, moderately differentiated and poorly differentiated gastric cancer (18.6% and 23.8% vs 5.8%, p = 0.047). Conclusion: We applied successfully FISH and IHC technique with biopsy samples in gastric cancer detecting HER2/neu positivity in order to select patients that benefit from trastuzumab in combination with chemotherapy. HER2/neu status associated with tumor location, Lauren classification and differentiated grading. Keywords: gastric cancer, fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), HER-2/neu

A PILOT STUDY OF HER-2/NEU GENE AMPLIFICATION ASSESSED BY FLUORESCENCE IN SITU HYBRIDIZATION (FISH) IN GASTRIC CANCER

2014 ◽  
pp. 15-20
Author(s):  
Van Huy Tran ◽  
Thi Minh Thi Ha ◽  
Trung Nghia Van ◽  
Viet Nhan Nguyen ◽  
Phan Tuong Quynh Le ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Cancer Patients ◽  
Gene Amplification ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Her 2 ◽  
Gastric Cancer Patients

Background: HER-2/neu is a predictive biomarker for treatment of gastric cancer using trastuzumab in combination with chemotherapy. This study aimed to evaluate the status of HER-2/neu gene amplification using fluorescence in situ hybridization (FISH) in gastric cancer. Patients and methods: thirty six gastric cancer patients were assessed HER-2/neu gene amplification by FISH using PathVysionTM HER-2 DNA Probe kit (including HER-2/neu probe and CEP-17 probe) with biopsy and surgical specimens. Results: The HER-2/neu gene amplification was observed in three cases (8.3%), the HER-2/neu gene amplification rate in Lauren’s intestinal-type and diffuse-type were 11.8% and 5.2%, respectively. Conclusion: We applied successfully FISH technique with gastric cancer tissue samples. This technique could be performed as routine test in gastric cancer in order to select patients that benefit from trastuzumab in combination with chemotherapy.

scholarly journals Extranodal NK/T-cell lymphoma in Tunisia: clinicopathological features, immunophenotype and EBV infection

2019 ◽  
Vol 31 (1) ◽  
Author(s):  
Nabiha Missaoui ◽  
Sarra Mestiri ◽  
Aida Bouriga ◽  
Nihed Abdessayed ◽  
Mouna Belakhdher ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
T Cell ◽  
Granzyme B ◽  
Clinicopathological Features ◽  
Histopathological Diagnosis ◽  
Ebv Infection ◽  
Nk T Cell ◽  
Epstein Barr ◽  
Hodgkin's Lymphomas

Abstract Background Extranodal NK/T-cell lymphomas (ENKTL) are rare non-Hodgkin’s lymphomas with aggressive clinical behavior. ENKTL are frequently associated with the Epstein-Barr virus (EBV). Data on ENKTL in Africa and Arab world are extremely limited. The study investigated the clinicopathological characteristics, EBV infection, and immunophenotype of ENKTL in Tunisia. We conducted a retrospective study of ENKTL. Main clinicopathological features were reported. The expression of CD3, CD4, CD5, CD8, CD20, CD56, CD57, and Granzyme B were analyzed by immunohistochemistry. EBV infection was detected by IHC (LMP-1) and Epstein-Barr encoding region (EBER1/2) in situ hybridization. Results A total of nine ENKTL were identified (mean age of 48 years and male-to-female ratio of 8:1). There were five nasal ENKTL, and the remaining four cases had extranasal involvement (palate, sub-mandibular gland, skin, and soft tissues of the ankle). The histopathology showed a lymphoid and pleomorphic proliferation characterized by images of angiocentrism. Strong and diffuse CD3 expression was observed in all cases. Tumor cells exhibited an expression of CD5 (two cases), CD8 (three cases), CD56 (six cases), CD57 (three cases), and Granzyme B (eight cases). All ENKTL cases were EBV-associated. Overall 5-year survival rate was 57%. Although six ENKTL were diagnosed at early clinical stages, the prognosis was unfavorable and associated with patient death in three cases. Conclusions ENKTL are exceptional in Tunisia with unfavorable outcome. Histopathological diagnosis remains challenging in clinical practice. However, a careful histopathological examination combined with a correct interpretation of immunohistochemistry and in situ hybridization results refines the ENKTL diagnosis.

scholarly journals VWCE as a potential biomarker associated with immune infiltrates in breast cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qin Huo ◽  
Zhenwei Li ◽  
Siqi Chen ◽  
Juan Wang ◽  
Jiaying Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Her2 Status ◽  
Cancer Tissue ◽  
M2 Macrophage ◽  
Breast Cancer Patients ◽  
Immune Infiltration ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Factor C

Abstract Purpose Von Willebrand Factor C and EGF Domains (VWCE) is an important gene that regulates cell adhesion, migration, and interaction. However, the correlation between VWCE expression and immune infiltrating in breast cancer remain unclear. In this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer. Methods The expression of VWCE was analyzed by the tumor immune estimation resource (TIMER) and DriverDB databases. Furthermore, genes co-expressed with VWCE and gene ontology (GO) enrichment analysis were investigated by the STRING and Enrichr web servers. Also, we performed the single nucleotide variation (SNV), copy number variation (CNV), and pathway activity analysis through GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB databases, and further verified the results using Quantitative Real-Time PCR (RT-PCR), Western blotting, and immunohistochemistry. Results The results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissues. We found that the expression level of VWCE was associated with subtypes, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status of breast cancer patients, but there was no significant difference in the expression of VWCE was found in age and nodal status. Further analyses indicated that VWCE was correlated with the activation or inhibition of multiple oncogenic pathways. Additionally, VWCE expression was negatively correlated with the expression of STAT1 (Th1 marker, r = − 0.12, p = 6e−05), but positively correlated with the expression of MS4A4A (r = 0.28, p = 0). These results suggested that the expression of VWCE was correlated with immune infiltration levels of Th1 and M2 macrophage in breast cancer. Conclusions In our study, VWCE expression was associated with a better prognosis and was immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker and correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer.

scholarly journals In situ analysis of FGFR2 mRNA and comparison with FGFR2 gene copy number by dual-color in situ hybridization in a large cohort of gastric cancer patients

2017 ◽  
Vol 21 (3) ◽  
pp. 401-412 ◽  
Author(s):  
Yasutoshi Kuboki ◽  
Christoph A. Schatz ◽  
Karl Koechert ◽  
Sabine Schubert ◽  
Janine Feng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
In Situ Hybridization ◽  
Cancer Patients ◽  
Copy Number ◽  
Gene Copy Number ◽  
In Situ Analysis ◽  
Gene Copy ◽  
Fgfr2 Gene ◽  
Gastric Cancer Patients

Improved Filter Method for Urine Sediment Detection of Urothelial Carcinoma by Fluorescence In Situ Hybridization

2007 ◽  
Vol 131 (10) ◽  
pp. 1574-1577 ◽  
Author(s):  
Isabelle Meiers ◽  
Harpreet Singh ◽  
Deloar Hossain ◽  
Kevin Lang ◽  
Lina Liu ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Urothelial Carcinoma ◽  
Urine Cytology ◽  
Filter Method ◽  
Urine Sediment ◽  
Specific Test ◽  
Significant Difference ◽  
Time Required

AbstractContext.—Fluorescence in situ hybridization (FISH) of voided urine sediment is a sensitive and specific test for the detection of urothelial carcinoma. The time required for slide preparation using the conventional cytospin method is lengthy.Objective.—To present an alternative to the conventional cytospin method.Design.—We compared the results of an improved filter monolayer method with published results of the conventional cytospin method. A total of 624 patients with cytology and FISH analyses were followed with cystoscopy and/ or bladder biopsy. Fluorescence in situ hybridization analysis was performed on 624 cases using fluorescence-labeled probes to the pericentromeric regions of chromosomes 3, 7, and 17 and band 9p21; cytology was also performed in all cases.Results.—A total of 217 (34.7%) of 624 patients had follow-up bladder biopsies, and 170 of these (78.3%) had urothelial carcinoma. The sensitivity for cancer detection was higher for FISH than for urine cytology (92.9% [158/ 170] for FISH vs 72.9% [124/170] for urine cytology, P = <5%). The specificity was equivalent for FISH and urine cytology (97.5% [443/454] for FISH vs 92.2% [419/454] for cytology). The sensitivity for FISH was better (92.9% vs 81%), and there was no significant difference in specificity (97.5% vs 96%) between the filter method and the conventional cytospin method. Unlike the conventional cytospin method, the filter method did not require multiple centrifugation and decantation steps or investment in dedicated equipment.Conclusions.—The improved filter method was faster, easier, and less expensive than published results with the conventional cytospin method with better sensitivity and equivalent specificity.

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