The expression of epidermal growth factor receptor 1 and human epidermal growth factor receptor 2 based on tumor location affect survival in gastric cancer

Abstract

To investigate the different expression of epidermal growth factor receptor 1 (EGFR) and human epidermal growth factor receptor 2 (HER2) in gastric cancer based on tumor locations and its impact on patients survival. Gastric cancer is heterogeneous disease, recent years have established a molecular classification and described distribution of molecular subtypes in stomach. However, the difference of EGFR and HER-2 expression among tumor location is still unknown. Between January 2010 and August 2014, 2477 consecutive patients with gastric cancer were treated in our surgery department. The tumor locations were classified into 4 groups: cardia, fundus, corpus, and antrum. Based on tumor locations, the clinicopathologic characteristics, EGFR and HER-2 expression, and follow-up data were analyzed by univariant analysis and Kaplan-Meier analysis retrospectively. There were difference of gender, age, Borrmann type, pathological type, differentiation, T-stage, tumor size, gastrectomy method, and complications among the locations. The positive rate of EGFR expression in fundus was 18.18%, which was lower than cardia (46.21%), corpus (43.62%), and antrum (48.83%) (P < .001). The 5-year survival rate in EGFR positive patients was 50.8%, which was significantly lower than EGFR negative patients (64.0%, P = .021). The positive rate of HER-2 expression in cardia was 48.15%, which was significantly higher than fundus (37.5%), corpus (35.45%), and antrum (38.54%) (P = .009), but HER-2 expression did not correlate with 5-year survive (P = .548). Our results suggest that there exist difference of EGFR and HER-2 expression based on tumor locations, and the distribution of EGFR impact on patients survival. Emphasizing the role of EGFR and HER-2 in the context of location contribute to make appropriate treatment strategy and improve prognosis of gastric cancer.

Abnormal arginine synthesis confers worse prognosis in patients with middle third gastric cancer

“…Next, we found that middle third gastric cancer was associated with increased tumor size, which was consistent with a retrospective study by Li et al involving 2477 gastric cancer patients [14]. Their study showed that tumors in the gastric body were larger (p = 0.009) and associated with lower grade of differentiation and deeper in ltration (T stage) than tumors in the cardia, fundus, and antrum [14]. In another independent cohort study that included gastric cancer patients from South Korea and the United States, the largest tumor size and deepest invasion depth were observed in upper third tumors, while middle third tumors were the second largest in size, and lower third tumors were the smallest [16].…”

Abnormal arginine synthesis confers worse prognosis in patients with middle third gastric cancer

“…This observation may be attributed to several factors associated with distal gastric cancer, including younger patient age, reduced intraoperative blood loss, relatively lower rate of lymph node metastasis, and a lower proportion of stage IV [ 12 , 13 ]. Previously, Li et al investigated the association between tumor location and patient prognosis in 2145 gastric cancer cases, and found that tumors located in the gastric body had a lower 5-year survival rate than tumors located in the gastric fundus, gastric cardia and antrum [ 14 , 15 ]. In addition, Liu et al showed that in 198 young gastric cancer patients, those with middle third tumors had a 50.6% overall survival rate, which was significantly lower than those with upper-third or lower-third tumors [ 15 ].…”

Cardia Gastric Cancer Is Associated With Increased PIK3CA Amplifications and HER2 Expression Than Noncardia Gastric Cancer According to Lauren Classification

“…HER2 expression is higher in the gastric cardia than in other locations of the stomach ( 6 ). The correlation between HER2 expression and Lauren’s histologic types remains controversial.…”

“…Genome-wide association studies have revealed that some single nucleotide polymorphisms (SNPs) are associated with noncardia GC only ( 4 ), while others have shown no difference in the SNPs between cardia and noncardia GC ( 5 ). In addition, HER2 expression has been reported to be higher in cardia GC than in noncardia GC ( 6 ). The correlation between HER2 expression and histologic types in GC is controversial; HER2 expression has been reported to be associated with intestinal-type GC in some studies ( 7 ), whereas other studies have indicated that HER2 expression was more common in diffuse-type GC ( 8 ).…”