Oncotarget

Research Papers:

PIK3CA mutations are associated with increased tumor aggressiveness and Akt activation in gastric cancer

Ji-Won Kim _, Hye Seung Lee, Kyung Han Nam, Soyeon Ahn, Jin Won Kim, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim and Keun-Wook Lee

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Oncotarget. 2017; 8:90948-90958. https://doi.org/10.18632/oncotarget.18770

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Abstract

Ji-Won Kim1,*, Hye Seung Lee2,*, Kyung Han Nam3, Soyeon Ahn4, Jin Won Kim1, Sang-Hoon Ahn5, Do Joong Park5, Hyung-Ho Kim5 and Keun-Wook Lee1

1Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea

2Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea

3Department of Pathology, Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, Korea

4Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea

5Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea

*These authors contributed equally to this work

Correspondence to:

Keun-Wook Lee, email: hmodoctor@snubh.org

Keywords: PIK3CA, mutation, AKT, expression, gastric cancer

Received: October 11, 2016     Accepted: June 10, 2017     Published: June 28, 2017

ABSTRACT

PIK3CA mutations are frequent in gastric cancer. However, their pathological and clinical implications are still unclear. We analyzed the clinicopathological characteristics according to the PIK3CA mutation status of patients with stage IB–IV disease who underwent gastrectomy between May 2003 and Dec. 2005 (cohort 1; n = 302) and of those with stage IV disease who received gastrectomy between Jul. 2006 and Dec. 2012 (cohort 2; n = 120). PIK3CA mutations were detected in 40 patients (13.2%) in cohort 1. In these patients, PIK3CA-mutant tumors were more frequently located in the upper third of the stomach (p = 0.021) and significantly showed poorly differentiated histology (p = 0.018) and increased lymphatic (p = 0.015), vascular (p = 0.005), and perineural invasion (p = 0.026). In addition, these tumors showed significantly increased lymphocyte and neutrophil infiltration in cancer stroma (p < 0.001), Epstein–Barr virus positivity (p < 0.001), and microsatellite instability (p = 0.015). Cytoplasmic Akt expression was significantly increased in these tumors (p = 0.001). In cohort 2, PIK3CA mutations were identified in 15 patients (12.5%). PIK3CA-mutant tumors showed significantly increased vascular invasion (p = 0.019) and microsatellite instability (p = 0.041). In addition, cytoplasmic Akt expression was also significantly increased (p = 0.018). However, in both cohorts, PIK3CA mutations were not associated with the prognosis of patients. In conclusion, PIK3CA mutations were associated with increased tumor aggressiveness, especially in locoregional disease, and Akt activation in gastric cancer. Our data suggest that PIK3CA-mutated gastric cancer is a distinct disease entity, which might need a different therapeutic approach.


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