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Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 883-893页

作者： Brendha Cação Coimbra Marina Alessandra Pereira Leonardo Cardili Venancio Avancini Ferreira Alves evandro sobroza de mello Ulysses Ribeiro Jr Marcus Fernando Kodama Pertille Ramos department of Gastroenterology Instituto do CancerHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloFaculdade de MedicinaUniversidade de São PauloSão Paulo 01246000Brazil department of Pathology Instituto do CancerHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSão Paulo 01246000Brazil

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological *** We retrospectively reviewed 284 GC patients who underwent ***-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive *** PD-L1+PT staged as pN+were also tested for PD-L1 expression in their ***-L1(-)GC with pN+served as the comparison *** Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the *** PD-L1(-)PT,9.1%(4/44)had PD-L1+in the *** agreement between PT and LNM had a kappa value of *** tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both *** was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched *** disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

关键词： Gastric cancer Lymph node Programmed death ligand 1 Stomach neoplasms Immunohistochemistry Metastasis

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Expression profiles of gastric cancer molecular subtypes in remnant tumors

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World Journal of Gastrointestinal Oncology 2021年第4期13卷 265-278页

作者： Marcus Fernando Kodama Pertille Ramos Marina Alessandra Pereira Leonardo Cardili evandro sobroza de mello Ulysses Ribeiro Jr Bruno Zilberstein Ivan Cecconello department of Gastroenterology Instituto do CancerHospital das ClinicasHCFMUSPFaculdade de MedicinaUniversidade de São PauloSão Paulo 01249000São PauloBrazil department of Pathology Instituto do CancerHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de São PauloSão Paulo 01249000São PauloBrazil

BACKGROUND Remnant gastric cancer(RGC)is a carcinoma arising in the stomach remnant after previous gastric *** is frequently reported as a tumor with a poor prognosis and distinct biological features from primary gastric cancer(PGC).However,as it is less frequent,its profile regarding the current molecular classifications of gastric cancer has not been *** To evaluate a cohort of RGC according to molecular subtypes of GC using a panel of immunohistochemistry and in situ hybridization to determine whether the expression profile is different between PGC and *** Consecutive RGC patients who underwent gastrectomy between 2009 and 2019 were assessed using seven GC panels:Epstein-Barr virus in situ hybridization,immunohistochemistry for mismatch repair proteins(MutL homolog 1,MutS homolog 2,MutS homolog 6,and PMS1 homolog 2),p53 protein,and E-cadherin *** characteristics and survival of these patients were compared to 284 PGC *** A total of 40 RGC patients were enrolled in this *** to PGC,older age(Pdex(P=0.010),and lower hemoglobin level(Pde Metastasis stage between the *** the profiles evaluated,EBV-positive tumors were higher in RGC compared to PGC(P=0.039).The frequency of microsatellite instability,aberrant p53 immunostaining,and loss of E-cadherin expression were similar between RGC and *** rates of simultaneous alterations in two or more profiles were observed in RGC compared to PGC(Pdefined as EBV in nine(22.5%)cases,microsatellite instability in nine(22.5%)cases,genomically stable in one(2.5%)case,and chromosomal instability in 21(52.5%)*** was no significant difference in survival between molecular subtypes in RGC *** RGC w

关键词： Stomach neoplasms Gastric remnant Gastric remnant cancer Adenocarcinoma Immunohistochemistry

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Immunohistochemical expression of thymidylate synthase and prognosis in gastric cancer patients submitted to fluoropyrimidine-based chemotherapy

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Chinese Journal of Cancer Research 2018年第5期30卷 526-536页

作者： Marina Alessandra Pereira Marcus Fernando Kodama Pertille Ramos ANDre Roncon Dias Sheila Friedrich Faraj Cinthya dos Santos Cirqueira evandro sobroza de mello Bruno Zilberstein Venancio Avancini Ferreira Alves Ulysses Ribeiro Jr department of Gastroenterology Cancer InstituteUniversity of Sao Paulo Medical School department of Pathology Cancer InstituteUniversity of Sao Paulo Medical School department of Pathology Instituto Adolfo Lutz

Objective： Adjuvant chemotherapy with 5-fluorouracil （5-FU） has been widely used in gastric cancer （GC） patients to prevent relapse after curative resection. 5-FU acts by inhibiting thymidylate synthase （TS）, and high levels of TS correlate with resistance to treatment with fluoropyfimidines. The aim of this study was to evaluate the expression of TS in GC patients, and its relation with clinicopathological characteristics and prognosis in adjuvant chemotherapy with 5-FU. Methods： We retrospectively evaluated 285 patients who underwent D2-gastrectomy with curative intent. TS expression was determined by immunohistochemistry （IHC） in tumor cells by tissue microarray （TMA）. TS level was evaluated according to the intensity and percentage of cells marked by a score system. Patients were divided in three groups according to their TS-score： negative, low and high. Results： TS expression was positive in 92.3% of GC. TS-high, TS-low and TS-negative were observed in 46.3%, 46.0% and 7.7% of patients, respectively. High-TS GC were associated with older age （P=0.007）, high neutrophil/lymphocyte ratio （P=0.048）, well/moderately differentiated histology （P=0.001）, intestinal Lauren type （P〈0.001） and absence of perineural invasion （P=0.003）. Among 285 patients, 133 stage IUIII patients （46.7%） received chemotherapy with 5-FU. In survival analysis, TS-high was associated with worse disease-free survival （DFS） in stage III GC patients who received 5-FU-based chemotherapy （P=0.007）. Multivariate analysis revealed that total gastrectomy, poorly differentiated tumors and high TS-score were associated with worse DFS in stage III GC patients. Conclusions： High TS-score in stage III GC was associated with poor DFS in patients treated with fluoropyrimidine-based chemotherapy.

关键词： Gastric cancer adjuvant therapy thymidylate synthase 5-fluorouracil-based chemotherapy

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Prognostic implications of tumor-infiltrating lymphocytes in association with programmed cell death ligand 1 expression in remnant gastric cancer

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Chinese Journal of Cancer Research 2022年第6期34卷 612-622页

作者： Marina Alessandra Pereira Marcus Fernando Kodama Pertille Ramos André Roncon Dias Leonardo Cardili Rafael Dyer Rodrigues de Moraes Renan Ribeiro E Ribeiro Venancio Avancini Ferreira Alves Bruno Zilberstein evandro sobroza de mello Ulysses Ribeiro Jr department of Gastroenterology Instituto do Cancer do Estado de Sao PauloHospital das ClinicasFaculdade de MedicinaUniversidade de Sao Paulo(ICESP-HCFMUSP)Sao PauloSP 01246-000Brazil department of Pathology Instituto do Cancer do Estado de Sao PauloHospital das ClinicasFaculdade de MedicinaUniversidade de Sao Paulo(ICESP-HCFMUSP)Sao PauloSP 01246-000Brazil

Objective:Remnant gastric cancer(RGC)is usually associated with a worse *** they are less common and very heterogeneous tumors,new prognostic and reliable determinants are required to predict patients’clinical course for *** study aimed to investigate the tumor-infiltrating lymphocytes(TILs)and programmed cell death ligand 1(PD-L1)status as prognostic biomarkers in a cohort of patients with RGC to develop an immunerelated ***:Patients with gastric cancer(GC)who underwent curative intent gastrectomy were retrospectively *** resections with histological diagnosis of gastric adenocarcinoma were enrolled in the *** risk score based on immune parameters was developed using binary logistic regression *** were divided into high-risk(HR),intermediate-risk(IR),and low-risk(LR)groups based on their immune *** markers(CD3+,CD4+/CD8+T cells and PD-L1)were selected for their potential prognostic,therapeutic value,and evaluated by immunohistochemistry(IHC).Results:A total of 42 patients with RGC were enrolled in the *** score based on immune parameters exhibited an accuracy of 79%[the area under the receiver operating characteristic curve(AUC)=0.79,95%confidence interval(95%CI),0.63-0.94,P=0.002],and the population was divided into 3 prognostic groups:10(23.8%)patients were classified as LR,15(35.7%)as IR,and 17(40.5%)as HR *** were no differences in clinicopathological and surgical characteristics between the three *** survival analysis,HR and IR groups had worse disease-free survival and overall survival rates compared to the LR *** the multivariate analysis,lymph node metastasis and the immune score risk groups were independent factors related to worse ***:A scoring system with immune-related markers was able to distinguish prognostic groups of RGC associated with ***,tumor-infiltrating immune lymphocytes and PD-L1 status may serve as a potential prognostic bi

关键词： Stomach neoplasms gastric remnant tumor-infiltrating lymphocytes immune microenvironment

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Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization:Analysis in western patients after curative-intent surgery

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World Journal of Clinical Oncology 2021年第8期12卷 688-701页

作者： Marcus Fernando Kodama Pertille Ramos Marina Alessandra Pereira evandro sobroza de mello Cinthya dos Santos Cirqueira Bruno Zilberstein Venancio Avancini Ferreira Alves Ulysses Ribeiro-Junior Ivan Cecconello department of Gastroenterology Instituto do CancerHospital das ClinicasHCFMUSPFaculdade de MedicinaUniversidade de São PauloSão Paulo 01249000Brazil department of Pathology Instituto do CancerHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de Sao PauloSão Paulo 01249000Brazil department of Pathology Instituto Adolfo LutzSão Paulo 01246000Brazil

BACKGROUND Gastric cancer(GC)is a highly heterogeneous disease,and the identification of molecular subtyping of gastric adenocarcinoma emerged as a promising option to define therapeutic strategies and prognostic ***,the costs and technical complexity of molecular methodologies remains an obstacle to its adoption,and their clinical significance by other approaches needs further *** To evaluate the clinicopathological characteristics and long-term survival of GC based on the subgroups of molecular classification by immunohistochemistry(IHC)and in situ hybridization(ISH).METHODS We retrospectively evaluated all patients who underwent D2-gastrectomy between 2009 and 2016 in a Western cohort of GC patients treated with curative *** instability(MSI)status,E-cadherin,and p53 expression were analyzed by IHC,and Epstein-Barr virus(EBV)by *** microarrays were constructed for *** characteristics and survival of GC were evaluated according to subtypes defined by The Cancer Genome Atlas(TCGA)Research Network Group and Asian Cancer Research Group(ACRG)classification *** A total of 287 GC patients were *** on IHC and ISH analysis,five profiles were defined as follows:E-cadherin aberrant(9.1%),MSI(20.9%),p53 aberrant(36.6%),EBV positivity(10.5%),and p53 normal(31%),which corresponded to tumors that showed no alteration in another profile.A flowchart according to the TCGA and ACRG classifications were used to define the subtypes,where clinical and pathological characteristics associated with GC subtypes were *** location(P<0.001),total gastrectomy(P=0.001),and intense inflammatory infiltrate(P<0.001)were characteristics related to EBV *** subtype was predominantly associated with advanced age(P=0.017)and the presence of comorbidities(P=0.011).While Laurén diffuse type(P<0.001)and advanced stage(P=0.029)were related to genomically stable(GS)*** tumors and mic

关键词： Stomach neoplasms Gastric cancer Translational medical research Molecular classification Immunohistochemistry Biomarkers

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Prognostic factors for progression of liver structural lesions in chronic hepatitis C patients

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World Journal of Gastroenterology 2008年第16期14卷 2522-2528页

作者： Liliana SC Mendes Marcelo E Nita Suzane K Ono-Nita evandro S mello Luiz Caetano da Silva Venancio AF Alves Flair J Carrilho department of Gastroenterology-Hepatology Branch University of So Paulo School of Medicine So Paulo 04537-040 So Paulo-SP Brazil department of Pathology University of So Paulo School of Medicine So Paulo 04537-040 So Paulo-SP Brazil

AIM: To evaluate the epidemiological, clinical, laboratory and histological variables capable of predicting the progression of hepatic structural disturbances in chronic hepatitis C patients during the time interval between two liver biopsies. METHODS: Clinical charts of 112 chronic hepatitis C patients were retrospectively analyzed, whereas liver biopsies were revised. Immunohistochemical detection of interferon receptor was based on the Envision-Peroxidase System. RESULTS: In the multivariate analysis, the variables in the age at first biopsy, ALT levels, presence of lymphoid aggregates and siderosis were the determinants of the best model for predicting the severity of the disease. The direct progression rate of hepatic structural lesions was significantly higher in untreated patients, intermediate in treated non-responders and lower in treated responders to antiviral therapy (non-treated vs responders, 0.22 ± 0.50 vs -0.15 ± 0.46, P = 0.0053). Immuno-expression of interferon receptor is not a relevant factor. CONCLUSION: The best predictors of the progression of fibrosis are age at the first liver biopsy, extent of ALT elevation, inflammation at liver histology and hepatic siderosis. Antiviral treatment is effective in preventing the progression of liver structural lesions in chronic hepatitis C patients.

关键词： Hepatitis C Histology Fibrosis Interfemns Disease progression

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