Prognostic Impact of CXCR7 and CXCL12 Expression in Patients with Esophageal Adenocarcinoma

2021 ◽  
Author(s):  
Masakazu Goto ◽  
Yukiko Shibahara ◽  
Cristina Baciu ◽  
Frances Allison ◽  
Jonathan C. Yeung ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Prognostic Impact ◽  
Cxcl12 Expression

243 PROGNOSTIC IMPACT OF CXCR7 AND CXCL12 EXPRESSION IN PATIENTS WITH ESOPHAGEAL ADENOCARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Masakazu Goto ◽  
Yukiko Shibahara ◽  
Cristina Baciu ◽  
Frances Allison ◽  
Mathieu Derouet ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
High Expression ◽  
Average Score ◽  
Prognostic Impact ◽  
Cell Trafficking ◽  
Multiple Cancer ◽  
Cxcl12 Expression ◽  
Potential Biomarker

Abstract   Chemokines are major regulators of cell trafficking and adhesion. The chemokine CXCL12 and its receptors, CXCR4 and CXCR7, have recently been reported as biomarkers in various cancers, including esophageal squamous cell carcinoma; however, there are few studies of these chemokines in esophageal adenocarcinoma (EAC). In this study, we investigated the relationship between expression of CXCL12, CXCR4 and CXCR7, and prognosis in patients with EAC. Methods This study examined 55 patients with EAC who were treated in Toronto General Hospital from 2001 to 2010. Tissue microarray immunohistochemistry was used to evaluate the expression of CXCL12, CXCR4 and CXCR7. Evaluation of immunohistochemistry was performed by a pathologist without knowledge of patients’ information and scored based on a semiquantitative scoring system. The average score from multiple cancer tissues on the microarray was utilized and patients were divided into high or low expression groups using the median score as a cutoff point. These results were compared with the patients’ clinicopathological features and survival. Results The score of CXCR7 was positively correlated with that of CXCL12 (r = 0.3154). High CXCR7 expression was significantly associated with lymphatic invasion (present vs absent, P = 0.005), higher number of lymph node metastases (pN0–1 vs pN2–3, P = 0.0014) and TNM stage (Stage I-II vs III-IV, P = 0.0168). Patients with high CXCR7 (n = 23) expression was associated with worse overall (OS) and disease-free survival (DFS) (P = 0.0221, 0.0090, respectively), and patients with high CXCL12 (n = 24) tended to have worse OS and DFS (P = 0.1091, 0.1477, respectively). High expression of both CXCR7 and CXCL12 was an independent prognostic factor for DFS on multivariable analysis (HR0.3, 95%CI: 0.1–0.8, P = 0.0115). Conclusion High CXCR7 expression was associated with poor prognosis in patients with EAC, and high expression of CXCR7 and its ligand CXCL12, had a stronger association on prognosis. Further study of this potential biomarker using whole tissue samples and larger sample size is warranted.

Prognostic Impact of the Presence of Barrett’s Esophagus and Intestinal Metaplasia on Esophageal Adenocarcinoma Survival

2021 ◽  
pp. 263451612110332
Author(s):  
Jennifer M. Kolb ◽  
Charlie Fox ◽  
Chloe Friedman ◽  
Frank I. Scott ◽  
Samuel Han ◽  
...  
Keyword(s):  
Overall Survival ◽  
Intestinal Metaplasia ◽  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Barrett's Esophagus ◽  
Clinical Stage ◽  
Tertiary Care ◽  
Prognostic Impact ◽  
Group I ◽  
Stage 4

Background/Aims: Barrett’s esophagus (BE), defined by the presence of intestinal metaplasia (IM) on histology, is thought to be the only identifiable precursor lesion for esophageal adenocarcinoma (EAC). Recent studies have suggested the possibility of an alternate, non-IM associated EAC that is a more aggressive form of EAC with worse survival. Among EAC patients, we aimed to compare survival of patients with and without IM at the time of diagnosis. Methods: This was a retrospective cohort study of all patients with histologic confirmed EAC evaluated at a tertiary care center from 2013 to 2019. Cases were categorized according to the presence or absence of IM on histologic specimens (Group I—IM-EAC and Group II—non-IM-EAC). We compared demographic characteristics, clinical stage, therapy, and survival between the 2 groups using the Chi-square and ANOVA tests (for categorical and continuous variables, respectively). We used Cox proportional hazards regression to determine the association of IM with overall survival, adjusting for sex, age at diagnosis, tumor location, histologic grade, and clinical stage. Results: A total of 475 patients were included in this analysis (mean age 64.8 years [SD 10.8], 89% white) and 109 (23.0%) had no evidence of IM. Compared with IM-EAC (Group I), individuals in the non-IM-EAC group were younger ( P = .01) and had a greater proportion of patients diagnosed with advanced disease (49.5 vs 20.2% for stage 4, P < .001). These patients were less likely to undergo endoscopic therapy alone (0.92% vs 29.78%, P < .001) or surgery alone (0 vs 9.84%, P = .001). On multivariable analysis, the presence of IM-EAC was associated with improved overall survival compared to non-IM-EAC (HR 0.69, 95% CI 0.49-0.96). Additional factors associated with poor survival was increasing stage of diagnosis (HR 6.49: 95% CI 3.77-11.15 for stage 4, HR 2.19: 95% CI 1.25-3.84 for stage 3, HR 2.04: 95% CI 0.98-4.25 for stage 2 compared to stage 1) and more advanced histologic stage (HR 2.00, 95% CI 1.26-3.19) for poorly/undifferentiated compared to well differentiated). Conclusions: EAC without the presence of IM on histology was associated with worse survival compared to those with IM. Future prospective studies with detailed molecular sequencing are required to clarify if 2 separate phenotypes of EAC exist (IM-EAC and non-IM-EAC). If confirmed, this may have significant implications for screening and management strategies.

Lymph node invasion might have more prognostic impact than R status in advanced esophageal adenocarcinoma

2013 ◽  
Vol 205 (6) ◽  
pp. 711-717 ◽  
Author(s):  
Magali Cabau ◽  
Guillaume Luc ◽  
Eric Terrebonne ◽  
Geneviève Belleanne ◽  
Véronique Vendrely ◽  
...  
Keyword(s):  
Lymph Node ◽  
Esophageal Adenocarcinoma ◽  
Prognostic Impact

scholarly journals Prognostic Impact of Body Mass Index Stratified by Smoking Status in Patients With Esophageal Adenocarcinoma

2011 ◽  
Vol 29 (34) ◽  
pp. 4561-4567 ◽  
Author(s):  
Harry H. Yoon ◽  
Mark A. Lewis ◽  
Qian Shi ◽  
Maliha Khan ◽  
Stephen D. Cassivi ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Esophageal Adenocarcinoma ◽  
Body Mass ◽  
Cox Regression ◽  
Smoking Status ◽  
Disease Free Survival ◽  
Normal Weight ◽  
Prognostic Impact ◽  
Free Survival ◽  
Never Smokers

Purpose Given that smoking affects body mass index (BMI) and survival, stratification by smoking status may be required to determine the true prognostic impact of BMI. Although obesity increases risk for developing esophageal adenocarcinoma (EAC), the prognostic influence of obesity and its potential modification by smoking status is unknown in this disease. Patients and Methods All patients (N = 778) underwent potentially curative esophagectomy. BMI was calculated using measured height and weight at surgery and categorized as obese (≥ 30 kg/m2), overweight (25 to 29.9 kg/m2), or normal (18.5 to 24.9 kg/m2). Cigarette smoking was categorized as never or ever. The association of BMI with disease-specific survival (DSS), disease-free survival (DFS), and overall survival (OS) was determined by Cox regression. Results Excess BMI was significantly associated with DSS in a manner that differed substantially by smoking status (P for interaction = .023). Among never smokers, obesity was significantly associated with adverse DSS (hazard ratio [HR] = 2.11; 95% CI, 1.31 to 3.43; P = .002), DFS (HR = 2.03; 95% CI, 1.30 to 3.18; P = .002), and OS (HR = 1.97; 95% CI, 1.24 to 3.14; P = .004), as compared with normal weight, after adjusting for covariates. By contrast, among ever smokers, obesity was not prognostic, and overweight status was significantly associated with favorable survival in univariate, but not multivariate, analysis. Conclusion Obesity among never smokers was independently associated with two-fold worsening of DSS, DFS, and OS after surgery for EAC, after adjusting for known prognostic factors. These data, in one of the largest reported resected EAC cohorts, are the first to show an adverse prognostic impact of obesity in EAC.

PS02.197: UPREGULATION OF IMP3 HAS A NEGATIVE PROGNOSTIC IMPACT IN EARLY INVASIVE ESOPHAGEAL ADENOCARCINOMA

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 178-178
Author(s):  
Patrick Plum ◽  
Dita Ulase ◽  
Seung-Hun Chon ◽  
Felix Berlth ◽  
Thomas Zander ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Esophageal Adenocarcinoma ◽  
Conflicts Of Interest ◽  
Locally Advanced ◽  
Tumor Grade ◽  
Staining Intensity ◽  
Prognostic Impact ◽  
Small Series ◽  
Therapeutic Decisions ◽  
Advanced Tumors

Abstract Background Despite improvements in perioperative treatments, the overall survival of patients with esophageal adenocarcinoma (EAC) remains low. In early invasive tumors (pT1) there is striking risk discrepancy for tumors with vascular invasion (L1/V1). As this tumor stage is potentially locally resectable, there is an urgent need for reliable pretherapeutical evaluation. High expression of IMP3 correlates with worse prognosis in colon and gastric cancer. In a small series of 30 patients with EAC, IMP3 is significantly associated with lymphovascular invasion. In our large cohort of EAC, we analyzed the immunohistochemical expression of IMP3 in correlation to clinical data. Methods 371 patients who underwent esophagectomy due to EAC at the Department of General, Visceral and Cancer Surgery, University of Cologne between 1999 and 2012 were included. Tissue Microarrays (TMA) were retrospectively established from the formalin-fixed, paraffin embedded material of the resected specimens and immunohistochemically stained using the primary antibody specific for IMP3. The IMP3 staining intensity was scored manually according to a 3-tier-scoring system (negative, weak and strong). Results TMAs from 371 patients were interpretable for further analysis. 109 patients (29.3%) had superficial EAC (pT1a/pT1b) while 262 (70.7%) showed locally advanced tumors (pT2 or pT3). 67 (26.7%) patients with advanced tumors and all pT1 EAC patients did not receive neoadjuvant therapy (chemotherapy or chemo-radiotherapy) prior to surgery. 259 of the 371 EAC revealed positive immunostaining for IMP3 including 167 strongly and 92 weakly positive. For patients without neoadjuvant therapy, there was a significant trend for higher IMP3 expression in early invasive tumors (pT1a/pT1b) showing significantly higher rates of IMP3 positive tumors compared to locally advanced pT3-tumors without neoadjuvant therapy (P = 0.0015). There was no difference of IMP3 expression according to neoadjuvant therapy in patients with pretreated EAC. There is a statistically significant association between IMP3 protein expression and shortened survival in early invasive pT1-esophageal carcinomas (P = 0.045). Conclusion IMP3 is a feasible marker in early invasive EAC (pT1a and pT1b) and is significantly associated with worse outcome. IMP3 indicates lymph node metastases, advanced infiltration depth and higher tumor grade. Thus IMP3 might be useful for therapeutic decisions in early invasive EAC. Disclosure All authors have declared no conflicts of interest.

scholarly journals Adverse Prognostic Impact of Intratumor HeterogeneousHER2Gene Amplification in Patients With Esophageal Adenocarcinoma

2012 ◽  
Vol 30 (32) ◽  
pp. 3932-3938 ◽  
Author(s):  
Harry H. Yoon ◽  
Qian Shi ◽  
William R. Sukov ◽  
Mark A. Lewis ◽  
Christopher A. Sattler ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Esophageal Adenocarcinoma ◽  
Gene Amplification ◽  
Prognostic Impact ◽  
Her2 Amplification ◽  
Her2 Gene ◽  
Cox Models ◽  
Node Number ◽  
Polysomy 17 ◽  
Her2 Heterogeneity

PurposeThere is increasing recognition of the existence of intratumoral heterogeneity of the human epidermal growth factor receptor (HER2), which affects interpretation of HER2 positivity in clinical practice and may have implications for patient prognosis and treatment. We determined the frequency and prognostic impact of heterogeneous HER2 gene amplification and polysomy 17 in patients with esophageal adenocarcinoma (EAC).Patients and MethodsHER2 amplification (by fluorescence in situ hybridization) was examined in surgical EAC specimens (n = 675). HER2 heterogeneity was defined according to consensus guidelines as gene amplification (HER2/CEP17 ratio ≥ 2.0) in more than 5% but less than 50% of cancer cells. No patient received neoadjuvant or HER2-targeted therapy. Cox models were used to assess disease-specific survival (DSS) and overall survival (OS).ResultsOverall, 117 EACs (17%) demonstrated HER2 amplification, of which 20 (17%) showed HER2 heterogeneity. All HER2-heterogeneous tumors were amplified. Among HER2-amplified tumors, heterogeneous tumors had significantly higher frequency of poor histologic grade and polysomy 17. In multivariable models that included number of metastatic lymph nodes, grade, tumor stage, and polysomy 17, only HER2 heterogeneity and node number were prognostic among HER2-amplified tumors, with heterogeneity showing worse DSS (hazard ratio, 2.04; 95% CI, 1.09 to 3.79; P = .025) and OS (P = .026). Among HER2-nonamplified EACs, polysomy 17 was independently associated with worse DSS (P = .012) and OS (P = .023).ConclusionAmong HER2-amplified EACs, 17% show HER2 heterogeneity, which independently predicts for worse cancer-specific death. Among HER2-nonamplified EACs, polysomy 17 is independently associated with worse survival. These novel findings demonstrate aggressive subgroups in HER2-amplified and -nonamplified EACs that have important implications for HER2 analysis and determination of benefit from HER2-targeted therapy.

scholarly journals The prognostic impact ofO6-Methylguanine-DNA Methyltransferase (MGMT) promotor hypermethylation in esophageal adenocarcinoma

2006 ◽  
Vol 119 (2) ◽  
pp. 264-268 ◽  
Author(s):  
S. Baumann ◽  
G. Keller ◽  
F. Pühringer ◽  
R. Napieralski ◽  
M. Feith ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Dna Methyltransferase ◽  
Prognostic Impact ◽  
Methylguanine Dna Methyltransferase

PS02.058: EXTENSIVE ANALYSIS OF IMMUNECHECKPOINT RECEPTORS AND TUMOR INFILTRATING T-CELLS WITH RESPECT TO THEIR PROGNOSTIC RELEVANCE IN ESOPHAGEAL ADENOCARCINOMA

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 137-137
Author(s):  
Florian Gebauer ◽  
Heike Loeser ◽  
Hans Fuchs ◽  
Jessica Leers ◽  
Wolfgang Schroeder ◽  
...  
Keyword(s):  
T Cells ◽  
Esophageal Adenocarcinoma ◽  
Survival Data ◽  
Conflicts Of Interest ◽  
Molecular Data ◽  
Immune Checkpoints ◽  
Prognostic Impact ◽  
Checkpoint Inhibition ◽  
Extensive Analysis

Abstract Background Immunotherapy has grown to a rapidly advancing sphere of research on modern strategies for treatment of cancer. A well-known way of immunomodulation is the principle of immune checkpoints leading to a down-regulated immune response in tumor microenvironment. Recently, beside the PD1/PD-L1 pathway, several immunecheckpoint pathways have been found. However, almost nothing is known about the expression and the correlation as prognostic factor in esophageal adenocarcinoma. Methods Two tissue micro arrays (TMA) were construced, a multi-spot TMA with up to 8 spots from different tumor areas of 165 patients and a valdiation single-spot TMA of 620 patients with EAC. Immunehistochemistry analysis were performed for LAG3, Tim3, IDO, VISTA, MHC1, MHC2, CD3, CD8, CD20 and CD38 and correlated with clinico-pathological and survival data. Data were additionally correlated with molecular data like TP53 mutational and HER2-neu status. Results LAG3 was detectable in 13.5% of all tumors, VISTA in 40.2%, IDO in 57.9%, Tim3 in 36.3%. There was only minor intratumoral heterogeneity between the luminal and infiltration area of the tumor for all analyzed immunecheckpoints. LAG3 and VISTA expression on tumor infiltrating T-cells (TIL) was associated with superior overall-survival compared to LAG3 and VISTA negative tumors. In pT1/2 tumors, VISTA was found as excellent independent prognosticator identifiying long-term surivors in case of VISTA expression. High amount of CD3 positive TILs was also associated with a better OS than CD3 poor tumors. Conclusion We conducted an extensive analysis of the immunecheckpoint status and presecnce of TILs in EAC. To the best of our knowledge, this is the first report in a large patients cohort correlating the expression of LAG3, Tim3, IDO and VISTA in EAC. The prognostic impact of LAG3 and VISTA expression suggests potential promising targets for novel immune checkpoint inhibition therapies beyond the PD1/PD-L1 inhibition as it is already established in head and neck cancer and NSCLC. Disclosure All authors have declared no conflicts of interest.

PS02.092: HER2 EXPRESSION AND GENE AMPLIFICATION CORRELATES WITH BETTER SURVIVAL IN ESOPHAGEAL ADENOCARCINOMA

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 146-147
Author(s):  
Heike Loeser ◽  
Patrick Plum ◽  
Thomas Zander ◽  
Max Kraemer ◽  
Hakan Alakus ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Esophageal Adenocarcinoma ◽  
Gene Amplification ◽  
Growth Pattern ◽  
Prognostic Impact ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Papillary Tumor ◽  
The Impact

Abstract Background Targeting Her2 is highly established in cancers of the upper gastrointestinal tract, since clinical studies showed a survival benefit in Her2-positive gastric cancer. To date there is conflicting data concerning the impact of Her2 expression and gene amplification in esophageal adenocarcinoma (EAC), as most studies do not differ between cancers of the esophagus, gastroesophageal junction and stomach. The aim of this study was to analyze the expression and gene amplification of Her2 in EAC in correlation to clinical and pathological data to verify the prognostic impact. Methods We analyzed 506 patients with esophageal adenocarcinomas that underwent thoraco-abdominal esophagectomy between 1997 and 2013 using a tissue micro array (TMA) for the expression of Her2 by immunohistochemistry (IHC) according to the guidelines. Fluorescence-in-situ-hybridization (FISH) was performed for IHC score 2. The Her2-status was correlated with clinical and pathological data. Results Her2-positivity was found in 11.7% (n = 59) of all EAC (IHC score 3 + or IHC score 2 + with amplification) and demonstrated a significant better overall-survival (OS) in correlation to Her2-negative tumors (median OS 55.0 vs. 22.7 months, P < 0.0001) (Figure below). Overexpression of Her2 was associated with lower tumor stages (pT1/pT2, P = 0.038), absence of lymph node metastases (pN0/pN + , P = 0.030) and was significantly associated with tubular and/or papillary tumor growth pattern (P = 0.029). Conclusion We demonstrated a positive prognostic impact of Her2 expression and gene amplification in a large cohort of EAC, contrary to other solid malignancies including gastric cancer, but according to a large study of EAC from 2012. Her2-positive tumors significantly have a tubular and/or papillary tumor growth pattern, indicating a marker of differentiation in EAC. Disclosure All authors have declared no conflicts of interest.

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