PIK3CA mutations are frequently observed in gastric cancer (GC). However, their pathologic and clinical implications have not been well understood yet.
Clinical and pathological data of patients with stage I-IV GC who underwent gastrectomy between May 2003 and December 2005 were retrospectively analyzed according to their PIK3CA mutation status using real-time polymerase chain reaction.
A total of 302 patients (male, 202) were included and the median age of patients was 61 years (range, 29-89). PIK3CA mutations were detected in 40 patients (13%). Compared with PIK3CA wild-type tumors, cytoplasmic expression of Akt was significantly increased in PIK3CA mutant tumors [immunohistochemstry 3 + : 17% (mutant) vs. 2% (wild type); p = 0.001]. PIK3CA mutant tumors were more likely to be located in the upper third of stomach (37% vs. 18%; p = 0.021) and presented with more advanced T stage (pT4: 53% vs. 33%; p = 0.018). PIK3CA mutant tumors were significantly associated with poorly differentiated histology (73% vs. 46%; p = 0.018), and increased lymphatic (93% vs. 75%; p = 0.015), vascular (35% vs. 16%; p = 0.005), and perineural invasion (73% vs. 54%; p = 0.026). In addition, these tumors exhibited significantly more lymphocyte and neutrophil infiltration in stroma (p
PIK3CA mutations up-regulate Akt expression and seem to confer aggressive tumor biology in GC. These data suggest that PIK3CA-mutated GC may be a distinct disease entity. However, the existence of PIK3CA mutation was not associated with poor prognosis in GC patients receiving gastrectomy.
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This study was partially supported by research grants from the Seoul National University Bundang Hospital Research Fund (02-2015-009).
All authors have declared no conflicts of interest.