Correlation Of Claudin18 With Clinicopathological Characteristics Of Gastric Cancer

Background:Gastric cancer is the second most common cancer in China,manifested as high morbidity and mortality,and this feature also means that gastric cancer not only has a high proportion of patients,but also has an extremely limited treatment,with unsatisfactory efficacy,which has also been confirmed in clinical practice.On the one hand,due to the high proportion of patients with advanced gastric cancer in China,only 15%of patients are diagnosed with stage Ⅰ,while the proportion of patients with stage IV is as high as 38.5%.These patients lose the chance of surgery and have metastasis,mainly to prolong survival with comprehensive treatment;On the other hand,there is a lack of effective treatment for advanced gastric cancer.Claudin18 is a member of the Claudin family expressed at epithelial tight junctions and is considered a highly attractive biomarker for targeted therapy because of its tissue specificity.Claudin-18 has been found to be closely related to the development of gastric cancer,and major breakthroughs have also been made in the treatment targeting Claudin-18.2.So far,the clinical trial data related to claudin-18 are mainly obtained from Europe,and there is still much vacancies in Asian data.Therefore,we used clone 34H14L15 detection antibody to establish the prevalence of Claudin-18 expression in tissue samples taken from Shandong Provincial Hospital,and identify a patient population who may benefit from the Claudin 18 targeted therapy in the Chinese population.Method:Claudin 18 expression was investigated in tissue samples from patients with gastric adenocarcinoma archived at Shandong Provincial Hospital,between 2008 and 2010.Expression of Claudin-18 in tumor samples was evaluated by immunohistochemistry using the detection antibody(34H14L15)and analyzed according to a two-component scoring method:the intensity of staining(including complete basolateral as well as lateral membrane staining)and the percentage of tumor cells stained at the different staining intensities in relation to all tumor cells present in the respective tissue sample.The intensity of the staining was classified as 0,1+,2+,and 3+.Samples showing any specific staining with ≥ 1+intensity were defined as Claudin-18-positive.Results:Of the 185 samples analyzed,Claudin 18 was detected in 82.2%(n=152/185)of all primary tumors,and moderate-to-strong Claudin 18 expression(≥ 2+membrane staining intensity in≥40%of tumor cells)was observed in 52.4%(97/185)of primary tumors.Conclusions:There is no relationship between Claudinl 8 expression and age,sex,node metastasis,TNM stage and histological differentiation.Downregulation of Claudin18 expression is associated with poor survival outcomes.The high prevalence of Claudinl 8 among Chinese patients with GC supports the therapeutic assessment of zolbetuximab in this population.