Erzincan Binali Yıldırım ÜniversitesiErzincan Binali Yıldırım ÜniversitesiAçık Erişim Arşivi · RDL Open

Clinicopathologic Features and Prognostic Significance of Immunohistochemistry and In Situ Hybridization Based Molecular Classification in Gastric Carcinoma

ArticleAçık Erişim

Özet

Background/Aim: Gastric carcinoma (GC) is a highly heterogeneous disease with many subtypes that have different morphologic and molecular characteristics. In the current study, we analyzed immunohistochemical (IHC) and in situ hybridization (ISH) features of GCs and evaluated their association with prognosis and clinicopathological features. Materials and Methods: Three hundred cases analyzed by IHC and ISH for microsatellite stability, p53, e-cadherin, HER2, PD-L1 expression, and Epstein-Barr virus (EBV) status. Cases were classified into five subgroups based on expression profile. The relationships between subgroups, clinicopathological features, and survival were determined. Results: Ten (3.3%) cases were classified as EBV-associated, 45 (15%) as microsatellite instable (MSI), 73 (24.3%) as EBV–/microsatellite-stable (MSS)/epithelial−mesenchymal−transformation (EMT)-like, 75 (25%) as EBV–/MSS/non-EMT-like/p53+, and 97 (32.3%) as EBV–/MSS/non-EMT-like/p53–. The MSI subtype had the best overall survival (OS). In contrast, the EBV–/MSS/EMT-like subtype had the poorest OS. The MSI subtype was also related with old age of the patient and antrum-corpus localized tumors, whereas the EBV–/MSS/EMT-like was associated with young age, larger tumor size, and advanced stage presentation. PD-L1 positivity is highly correlated with MSI and EBV-associated subtypes. Conclusion: Our data demonstrated a link between IHC/ISH characteristics of GC and clinical outcomes. IHC/ISH based molecular classification may be helpful in predicting the survival. © 2023 by Begell House, Inc.

Anahtar Kelimeler

abnormal e-cadherin expressionabnormal p53 expressionCDH1 mutationEBV associated gastric cancermicrosatellite instabilitymolecular classification of gastric carcinomaB7-H1 AntigenCarcinomaEpstein-Barr Virus InfectionsHerpesvirus 4, HumanHumansImmunohistochemistryIn Situ HybridizationPrognosisStomach NeoplasmsTumor Suppressor Protein p53epidermal growth factor receptor 2programmed death 1 ligand 1protein p53uvomorulinadultageArticlecancer prognosiscancer sizecancer stagingcancer survivalclinical featureepithelial mesenchymal transitionEpstein Barr virus
RDL Kalıcı Bağlantı (PID)
https://rdlopen.rawdatalibrary.net/r/ebyu/12377Resmi atıflarda kullanılan kalıcı adres
Tam Kayıt
AlanDeğerDil
dc.contributor.authorIssin, Gizem
dc.contributor.authorSayar, İlyas
dc.contributor.authorDemir, Fatih
dc.contributor.authorBakkaloğlu, İrem Güvendir
dc.contributor.authorGamsizkan, Mehmet
dc.contributor.authorYildiz, Zeliha
dc.contributor.authorYilmaz, İsmail
dc.contributor.authorÖzmen, Sevilay Akalp
dc.contributor.authorÇağatay, Diren Vuslat
dc.contributor.authorZemheri, Itır Ebru
dc.contributor.authorDemiriz, Murat
dc.contributor.authorGünald, Armağan
dc.date.accessioned2026-10-18T20:27:17.119407209Z
dc.date.available2026-10-18T20:27:17.119407209Z
dc.date.issued2023
dc.description.abstractBackground/Aim: Gastric carcinoma (GC) is a highly heterogeneous disease with many subtypes that have different morphologic and molecular characteristics. In the current study, we analyzed immunohistochemical (IHC) and in situ hybridization (ISH) features of GCs and evaluated their association with prognosis and clinicopathological features. Materials and Methods: Three hundred cases analyzed by IHC and ISH for microsatellite stability, p53, e-cadherin, HER2, PD-L1 expression, and Epstein-Barr virus (EBV) status. Cases were classified into five subgroups based on expression profile. The relationships between subgroups, clinicopathological features, and survival were determined. Results: Ten (3.3%) cases were classified as EBV-associated, 45 (15%) as microsatellite instable (MSI), 73 (24.3%) as EBV–/microsatellite-stable (MSS)/epithelial−mesenchymal−transformation (EMT)-like, 75 (25%) as EBV–/MSS/non-EMT-like/p53+, and 97 (32.3%) as EBV–/MSS/non-EMT-like/p53–. The MSI subtype had the best overall survival (OS). In contrast, the EBV–/MSS/EMT-like subtype had the poorest OS. The MSI subtype was also related with old age of the patient and antrum-corpus localized tumors, whereas the EBV–/MSS/EMT-like was associated with young age, larger tumor size, and advanced stage presentation. PD-L1 positivity is highly correlated with MSI and EBV-associated subtypes. Conclusion: Our data demonstrated a link between IHC/ISH characteristics of GC and clinical outcomes. IHC/ISH based molecular classification may be helpful in predicting the survival. © 2023 by Begell House, Inc.
dc.description.sponsorshipFunding text 1: This retrospective study was conducted in accordance with the Declaration of Helsinki and received approval of the Erzincan Binali Yildirim University, Medical School Ethics Committee, Erzincan, Turkey. This study was supported by Erzincan University Scientific Research and Project Office (Project ID: 768).; Funding text 2: classifying completely immune-negative cases is to outcome compared to the cases with aberrant p53. evaluate them in the aberrant p53 group like ovary The ACRG study found a similar relationship be-carcinoma.4,5,26 tween the clinical outcomes of the MSS/TP53+ The study by Ando et al.24 revealed that strong and MSS/TP53-groups.3 The Cox regression model p53 staining in 70% or more of tumor nuclei was analysis of our data, however, did not find that aber-highly associated with the TP53 mutation. On the rant p53 expression was an independent prognostic other hand, they observed that only 20% of cases in factor for OS (HR = 1.053, 95% CI = 0.752–1.474, which less than 10% of tumor cells showed staining p = 0.763). had nonsense or missense mutations. And, for the rest 80% of these cases no-change in the structure of chromosome 17 (functionally active non-mutated p53 gene) have been detected. Pinto et al.27 docu- mented that most of the immune-negative cases had wild type TP53, however; frameshift insertion, non- sense, or missense mutations were observed in only 26% of cases that were completely immune-nega- tive. In contrast to the previous studies and general opinion, we concluded that for GCs, it would be more accurate to evaluate completely immune-neg- ative cases in the p53 negative group according to the results of Ando et al.24 and Pinto et al.27 In this study, we observed 3 di*甀erent p53 e-x pression types: 1. Completely p53 immune negative, 2. Patchy and weak nuclear expression, and 3. Dif- fuse and strong nuclear expression. According to the recommendation of Pinto et al.,27 we classified cases ACKNOWLEDGMENTS with di*甀use and strong expression in 20% or more This retrospective study was conducted in accor- of the tumor as EBV–/MSS/non-EMT-like/p53+ and dance with the Declaration of Helsinki and received the remaining cases as EBV−/MSS/non-EMT-like/ approval of the Erzincan Binali Yildirim Univer- p53–. Previous research showed that EBV−/MSS/ sity, Medical School Ethics Committee, Erzincan, non-EMT-like/p53+ GCs had more aggressive clin-Turkey. ical characteristics than EBV−/MSS/non-EMT-like/ This study was supported by Erzincan Univer- p53– GCs, such as higher tumor grade, more lymph sity Scientific Research and Project O*瘀ce (Project node involvement, and distant metastases.2,16,28 How-ID: 768). ever, Schoop et al.29 stated that p53 expression did not seem to be associated with survival or prognosis. Our findings partially support this result; the clinico- pathological characteristics of the EBV−/MSS/non- EMT-like/p53– and EBV−/MSS/non-EMT-like/p53+ groups were quite similar, including patient age, tu- mor site, histological grade, stage, and HER2 status, in our cohort. Furthermore, these groups had similar survival curves. The median OS of EBV−/MSS/non- EMT-like/p53-was 29 months, which was longer than the median OS of EBV−/MSS/non-EMT-like/ p53+ which was 25 months. Wang et al.16 reported that the GCs with normal p53 had a superior clinical
dc.identifier.doi10.1615/jenvironpatholtoxicoloncol.2023047662
dc.identifier.eissn2162-6537
dc.identifier.endpage14
dc.identifier.issn0731-8898
dc.identifier.issue4
dc.identifier.pmid37522564
dc.identifier.scopus2-s2.0-85165892012
dc.identifier.startpage1
dc.identifier.urihttps://rdlopen.rawdatalibrary.net/r/ebyu/12377
dc.identifier.volume42
dc.identifier.wosWOS:001074432700001
dc.language.isoen
dc.publisherBegell House Inc.
dc.relation.ispartofJournal of Environmental Pathology, Toxicology and Oncology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectabnormal e-cadherin expression
dc.subjectabnormal p53 expression
dc.subjectCDH1 mutation
dc.subjectEBV associated gastric cancer
dc.subjectmicrosatellite instability
dc.subjectmolecular classification of gastric carcinoma
dc.subjectB7-H1 Antigen
dc.subjectCarcinoma
dc.subjectEpstein-Barr Virus Infections
dc.subjectHerpesvirus 4, Human
dc.subjectHumans
dc.subjectImmunohistochemistry
dc.subjectIn Situ Hybridization
dc.subjectPrognosis
dc.subjectStomach Neoplasms
dc.subjectTumor Suppressor Protein p53
dc.subjectepidermal growth factor receptor 2
dc.subjectprogrammed death 1 ligand 1
dc.subjectprotein p53
dc.subjectuvomorulin
dc.subjectadult
dc.subjectage
dc.subjectArticle
dc.subjectcancer prognosis
dc.subjectcancer size
dc.subjectcancer staging
dc.subjectcancer survival
dc.subjectclinical feature
dc.subjectepithelial mesenchymal transition
dc.subjectEpstein Barr virus
dc.titleClinicopathologic Features and Prognostic Significance of Immunohistochemistry and In Situ Hybridization Based Molecular Classification in Gastric Carcinoma
dc.typeArticle
dspace.entity.typePublication
rdl.citation.scopus4
rdl.citation.wos4
rdl.departmentDepartment of Pathology, Erzincan Binali Yildirim University, Mengucek Gazi Training and Research Hospital, Erzincan, Turkey.
rdl.source.indexSCOPUS
rdl.source.indexWOS
rdl.source.indexPUBMED
rdl.wos.indexScience Citation Index Expanded (SCI-EXPANDED)