Chie Ito1, Satoshi S Nishizuka2, Kazuyuki Ishida3, Noriyuki Uesugi3, Tamotsu Sugai3, Gen Tamura4, Keisuke Koeda5, Akira Sasaki5. 1. Molecular Therapeutics Laboratory, Iwate Medical University School of Medicine, Iwate, Japan; Department of Surgery, Iwate Medical University School of Medicine, Iwate, Japan. 2. Molecular Therapeutics Laboratory, Iwate Medical University School of Medicine, Iwate, Japan; Department of Surgery, Iwate Medical University School of Medicine, Iwate, Japan; Division of Biomedical Research and Development, Institute of Biomedical Science, Iwate Medical University, Iwate, Japan. Electronic address: snishizu@iwate-med.ac.jp. 3. Department of Molecular Diagnostic Pathology, Iwate Medical University School of Medicine, Iwate, Japan. 4. Department of Pathology and Laboratory Medicine, Yamagata Prefectural Central Hospital, Yamagata, Japan. 5. Department of Surgery, Iwate Medical University School of Medicine, Iwate, Japan.
Abstract
BACKGROUND: Although surgery and chemotherapy have extended advanced gastric cancer patient survival, some patients still experience relapse and metastasis. We postulated that PI3K pathway proteins could be prognostic biomarkers for the advanced gastric cancer patients. METHODS: A retrospective cohort of 160 advanced gastric cancer patients receiving potentially curative surgery with/without chemotherapy was investigated for PIK3CA mutation and PI3K pathway protein level in the context of overall survival and relapse-free survival. RESULTS: Thirteen patients (13 of 111, 11.7%) had PIK3CA mutations in codon 545, whereas one patient (1 of 94, 1.1%) had a mutation in PIK3CA codon 1047. PI3K pathway protein immunohistochemistry demonstrated that phosphorylated AKT positive [p-AKT (+)] patients in the surgery-only group had a good prognosis in terms of overall survival and relapse-free survival. No significant association between PIK3CA mutations and PI3K pathway protein level was seen. CONCLUSIONS: This study revealed that (1) PIK3CA hotspot mutations occurred with low frequency in gastric cancer; (2) PIK3CA hotspot mutations were not directly associated with PI3K pathway activation; and (3) p-AKT (+) may be a biomarker for better outcomes for gastric cancer patients undergoing gastrectomy regardless of the PIK3CA mutation status.
BACKGROUND: Although surgery and chemotherapy have extended advanced gastric cancerpatient survival, some patients still experience relapse and metastasis. We postulated that PI3K pathway proteins could be prognostic biomarkers for the advanced gastric cancerpatients. METHODS: A retrospective cohort of 160 advanced gastric cancerpatients receiving potentially curative surgery with/without chemotherapy was investigated for PIK3CA mutation and PI3K pathway protein level in the context of overall survival and relapse-free survival. RESULTS: Thirteen patients (13 of 111, 11.7%) had PIK3CA mutations in codon 545, whereas one patient (1 of 94, 1.1%) had a mutation in PIK3CA codon 1047. PI3K pathway protein immunohistochemistry demonstrated that phosphorylated AKT positive [p-AKT (+)] patients in the surgery-only group had a good prognosis in terms of overall survival and relapse-free survival. No significant association between PIK3CA mutations and PI3K pathway protein level was seen. CONCLUSIONS: This study revealed that (1) PIK3CA hotspot mutations occurred with low frequency in gastric cancer; (2) PIK3CA hotspot mutations were not directly associated with PI3K pathway activation; and (3) p-AKT (+) may be a biomarker for better outcomes for gastric cancerpatients undergoing gastrectomy regardless of the PIK3CA mutation status.