Abstract 5485
Background
Signet ring cell carcinoma (SRCC), a subtype of gastric cancer (GC), has specific epidemiology and oncogenesis, and has poor prognosis; it still has the highest number of unmet medical needs. Cytoskeletal rearrangement and disruption of cell integrity play crucial roles in SRCC pathogenesis. Recently, many studies have been conducted on molecular alterations in SRCC; with the clarification of the clinical significance of the CLDN-ARHGAP fusion gene, a large clinical trial is underway. Herein, we examined the influence of CLDN, RhoGAP, and E-cadherin on SRCC prognosis.
Methods
We reviewed advanced 663 GC patients who received palliative chemotherapy. Of these, 135 patients (20.4%) were SRCC. Multiplexed immunofluorescence was performed on the tissue samples using antibodies against CLDN18, RhoGAP, and E-cadherin. Positivty was defined as the median value of H-score.
Results
Overall, 85 (63%) of 135 SRCC patients, were analysed based on tissue availability. Median age at GC diagnosis was 52.5 (range 20-77) years; the female-to-male ratio was 1.2. CLDN 18 showed a strong positive correlation with E-cadherin (r = 0.705, P < 0.001). E-cadherin expression was higher in the CLDN18 positive group than in the CLDN18 negative group (mean H-score, 74.9 ± 32.3 vs. 34.0 ± 30.4, P < 0.001). RhoGAP was positively correlated with E-cadherin (r = 0.354, P = 0.002). E-cadherin expression was higher in the RhoGAP positive group than the RhoGAP negative group (mean H-score, 64.5 ± 38.7 vs. 39.1 ± 29.2, P = 0.002). Overall survival (OS) was longer in the RhoGAP-negative group than in the RhoGAP positive group (median OS, 10.8 vs 6.2 months; P = 0.014). CLDN18 and E-cadherin positivity was not associated with prognosis. However, patients with RhoGAP (-)/E-cadherin (+) showed better OS than other patients (median OS, 12.1 vs 5.6 months, P = 0.003). Multivariate analysis with Cox survival regression showed that RhoGAP was found to be an independent poor prognostic factor (p = 0.041).
Conclusions
The correlations among CLDN18, RhoGAP, and E-cadherin may be associated with the discohesive oncogenesis seen in SRCC. We propose that these discohesive factors may be associated with prognosis of metastatic SRCC. Further functional studies are needed to clarify the role of these molecules.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3006 - Nal-iri/lv5-fu versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (OESIRI-PRODIGE 62): A FFCD multicenter, randomized, phase II study.
Presenter: Violaine Randrian
Session: Poster Display session 2
Resources:
Abstract
3697 - The expression of Versican and its role in pancreatic neuroendocrine tumor
Presenter: Zhao Sun
Session: Poster Display session 2
Resources:
Abstract
6073 - Characteristics of patients with thyroid carcinoma in the united states
Presenter: Dina El-Habashy
Session: Poster Display session 2
Resources:
Abstract
2124 - The discrimination of pituitary adenomas and craniopharyngioma on MRI: from image features to texture features
Presenter: Hanyue Xu
Session: Poster Display session 2
Resources:
Abstract
3786 - Proportion of Peripheral Lymphocyte Subsets Correlates with the Progression-free Survival and Metastatic Status of Pancreatic Neuroendocrine Tumor Patients
Presenter: Yitao Gong
Session: Poster Display session 2
Resources:
Abstract
2263 - Immunohistochemical expression of ER-α and PR in papillary thyroid carcinoma
Presenter: Enas Elkhouly
Session: Poster Display session 2
Resources:
Abstract
4386 - SILVELUL Project: Immunohistochemical panel analyses as potential predictive and prognostic factors in Pancreatic Neuroendocrine Tumors (PanNET) Treated with CAPTEM or Everolimus
Presenter: Ana De Jesus-Acosta
Session: Poster Display session 2
Resources:
Abstract
2302 - Carcinoid heart disease (CHD): the CRUSOE-NETs, a prospective cohort study from the French Group of Endocrine Tumors (GTE)
Presenter: Kathleen Dekeister Geoffroy
Session: Poster Display session 2
Resources:
Abstract
5749 - Safety of high doses of somatostatin analogs in well differentiated NENs in elderly
Presenter: Massimiliano Cani
Session: Poster Display session 2
Resources:
Abstract
3931 - Differences in multikinase inhibitors (MKI) toxicity profile according to gender. A pooled analysis of three phase II trials with lenvatinib, pazopanib and sorafenib in patients (pts) with advanced gastroenteropancreatic (GEP) neuroendocrine tumors (NETs).
Presenter: Jorge Hernando Cubero
Session: Poster Display session 2
Resources:
Abstract