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Tumor-infiltrating lymphocytes (TILs) have commonly been associated with markedly improved prognosis in a variety of human cancers, including carcinomas of the upper and lower gastrointestinal tract. Especially the presence of T-cells (cytotoxic as well as helper cells) seems to define a subgroup of patients with prolonged overall and event-free survival. The density of TILs was assessed via immunohistochemistry for CD8 and CD103 in a population of 228 adenocarcinomas of the esophagogastric junction. Density of CD8+ T-lymphocytes was inversely correlated with depth of tumor infiltration (p=0.013) while no correlation with any of the analyzed clinicopathologic factors could be established for CD103-density. High density of CD8-positive T-cells additionally showed significantly longer overall survival (OS) with a p-value of 0.024 while density of CD103+ cells was associated with prolonged tumor free survival (p-value 0.011). Independence could be demonstrated applying Cox proportional hazard analysis (Hazard Ratio 0.742; 95%-Confidence Interval 0.579-0.951; p=0.019). High density of CD8-positive T-lymphocytes identifies a patient subgroup with significantly prolonged overall survival, is correlated with tumor stage and might open up new therapeutic possibilities via immunomodulating drugs.

Introduction: In recent years antitumor immunity and inhibition of checkpoint molecules, such as PD-1 and PD-L1, have emerged as potential therapeutic strategies in advanced stages of various malignancies. We investigated PD-L1 expression in adenocarcinomas of the esophagogastric junction and correlated the results with densitiy of intratumoral T-lymphocytes., Methods: Immunohistochemical staining for PD-L1 was carried out on 135 samples using a tissue microarray. Scoring was done according to the combined positivity score., Results: 48.1% of tumors (65 cases) showed PD-L1 positivity with a score ≥ 1 while 51.9% were PD-L1 negative (70 cases). A positive correlation between PD-L1 negativity and mucinous and poorly cohesive carcinoma could be shown (p = 0.043), while no association existed for either gender, T-stage, N-stage, grading, surgical resection status, neoadjuvant therapy, distant metastases, lymphovascular or perineural invasion. No correlation of PD-L1 expression and overall survival could be detected (p = 0.497). Again, when stratified according to presence or absence of neoadjuvant therapy, no survival differences could be shown for either group (p = 0.540 and p = 0.736). When PD-L1 expression was correlated with density of tumor-infiltrating T-lymphocytes a positive correlation between PD-L1 positivity and denser T-cell infiltration could be shown (p = 0.001). Concerning overall survival, in PD-L1 negative cases, denser CD8-positive T-cell infiltrates were associated with prolonged survival times (p = 0.045). No differences could be shown for PD-L1 positive cases or CD103-positive T-cells., Conclusion: PD-L1 expression is frequent in esophagogastric adenocarcinoma and - when combined with dense CD8 infiltration - PD-L1 negativity correlates with prolonged overall survival., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: COX-2 expression induces carcinogenesis and is thought to be an adverse prognostic factor in gastric carcinomas while the prognostic value of DNA mismatch repair (MMR) is still controversial. Concerning adenocarcinomas of the esophagogastric junction, no comprehensive data regarding either factors are available as of yet., Objective: We assessed expression of COX-2, MLH1 and MSH2 in adenocarcinoma of the esophagogastric junction in relation to patients' survival and various clinicopathologic features., Design: Immunohistochemical studies (using antibodies against COX-2, MLH1 and MSH2) were performed in a study population of 228 tumours. Follow-up data was available for all patients with a mean follow-up time of 42.8 months., Results: 78 (34.2%) tumours were COX-2 negative, 148 (64.9%) showed COX-2 positivity. Assessment of COX-2 expression and clinicopathologic features revealed an inverse correlation with depth of tumour invasion and number of metastatic lymph nodes (p=0,021 and p=0,004, respectively). No correlation with other features could be demonstrated. 62 cases (27.2%) showed loss of DNA repair enzymes MLH1 and/or MSH2. MMR differed significantly between COX-2 positive and negative cases (p=0,028). Kaplan-Meier survival analyses revealed no impact on patients' survival for COX-2 expression or MMR status (p=0.837 and p=0.972, respectively)., Conclusions: Expression of COX-2 in adenocarcinomas of the esophagogastric junction seems to have no prognostic effect or impact on patients' survival but is associated with favourable clinicopathologic factors. MMR deficiency was more frequent in COX-2 negative tumours, but MMR status had no impact on survival and patients' outcome whatsoever.

Background: Tumor-infiltrating lymphocytes (TILs) have been shown to be of prognostic significance in a variety of tumors. Not only T-cell, but also B-cell infiltration is commonly associated with improved survival., Materials and Methods: We assessed the density of tumor-infiltrating B-cells, as well as that of plasma cells, in 210 adenocarcinomas of the esophagogastric junction through immunohistochemical analysis using antibodies against CD20 and CD138., Results: No correlation between density of B-cells or plasma cells and various clinicopathologic features could be established. High density of tumor-infiltrating B-cells, as well as plasma cells, showed significantly better overall survival (OS) compared to patients with no infiltrates (p=0.047 and p=0.022, respectively). Cox proportional hazard analysis could verify B-cell infiltration as an independent prognostic factor (hazard ratio (HR)=0.683; 95% confidence interval (CI)=0.517-0.901; p=0.007)., Conclusion: Plasma cell and B-cell infiltration correlates with prolonged OS and might identify a patient subset with favorable disease course., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Gauging the risk of developing progressive disease is a major challenge in prostate cancer patient management. We used genetic markers to understand genomic alteration dynamics during disease progression. By using a novel, advanced, multicolor fluorescence in situ hybridization approach, we enumerated copy numbers of six genes previously identified by array comparative genomic hybridization to be involved in aggressive prostate cancer [TBL1XR1, CTTNBP2, MYC (alias c-myc), PTEN, MEN1, and PDGFB] in six nonrecurrent and seven recurrent radical prostatectomy cases. An ERG break-apart probe to detect TMPRSS2-ERG fusions was included. Subsequent hybridization of probe panels and cell relocation resulted in signal counts for all probes in each individual cell analyzed. Differences in the degree of chromosomal and genomic instability (ie, tumor heterogeneity) or the percentage of cells with TMPRSS2-ERG fusion between samples with or without progression were not observed. Tumors from patients that progressed had more chromosomal gains and losses, and showed a higher degree of selection for a predominant clonal pattern. PTEN loss was the most frequent aberration in progressers (57%), followed by TBL1XR1 gain (29%). MYC gain was observed in one progresser, which was the only lesion with an ERG gain, but no TMPRSS2-ERG fusion. According to our results, a probe set consisting of PTEN, MYC, and TBL1XR1 would detect progressers with 86% sensitivity and 100% specificity. This will be evaluated further in larger studies., (Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)