Hatogai Ken, Fujii Satoshi, Kojima Takashi, Daiko Hiroyuki, Doi Toshihiko, Ohtsu Atsushi, Ochiai Atsushi, Takiguchi Yuichi, Yoshino Takayuki
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
BMC Cancer. 2017 Jan 9;17(1):36. doi: 10.1186/s12885-016-3041-3.
PIK3CA mutations are expected to be potential therapeutic targets for esophageal squamous cell carcinoma (ESCC). We aimed to clarify the concordance between PIK3CA mutations detected in endoscopic biopsy specimens and corresponding surgically resected specimens.
We examined five hotspot mutations in the PIK3CA gene (E542K, E545K, E546K, H1047R, and H1047L) in formalin-fixed and paraffin-embedded tissue sections of paired endoscopic biopsy and surgically resected specimens from 181 patients undergoing curative resection for ESCC between 2000 and 2011 using a Luminex technology-based multiplex gene mutation detection kit.
Mutation analyses were successfully performed for both endoscopic biopsy and surgically resected specimens in all the cases. A PIK3CA mutation was detected in either type of specimen in 13 cases (7.2%, 95% confidence interval: 3.9-12.0). The overall concordance rate, positive predictive value, and negative predictive value were 98.3% (178/181), 90.9% (10/11), and 98.8% (168/170), respectively. Among patients with a PIK3CA mutation detected in both types of specimens, the concordance between PIK3CA mutation genotypes was 100%. There were three cases with a discordant mutation status between the types of specimens (PIK3CA mutation in surgically resected specimen and wild-type in biopsy specimen in two cases, and the opposite pattern in one case), suggesting possible intratumoral heterogeneity in the PIK3CA mutation status.
The PIK3CA mutation status was highly concordant between endoscopic biopsy and surgically resected specimens from the same patient, suggesting that endoscopic biopsy specimens can be clinically used to detect PIK3CA mutations in patients with ESCC.
PIK3CA突变有望成为食管鳞状细胞癌（ESCC）的潜在治疗靶点。我们旨在明确内镜活检标本与相应手术切除标本中检测到的PIK3CA突变之间的一致性。
我们使用基于Luminex技术的多重基因突变检测试剂盒，检测了2000年至2011年间接受ESCC根治性切除的181例患者的配对内镜活检和手术切除标本的福尔马林固定石蜡包埋组织切片中PIK3CA基因的五个热点突变（E542K、E545K、E546K、H1047R和H1047L）。
所有病例的内镜活检和手术切除标本均成功进行了突变分析。13例（7.2%，95%置信区间：3.9 - 12.0）患者的任何一种标本中检测到PIK3CA突变。总体一致性率、阳性预测值和阴性预测值分别为98.3%（178/181）、90.9%（10/11）和98.8%（168/170）。在两种标本中均检测到PIK3CA突变的患者中，PIK3CA突变基因型之间的一致性为100%。有3例标本类型之间的突变状态不一致（2例手术切除标本中PIK3CA突变而活检标本中为野生型，1例情况相反），提示PIK3CA突变状态可能存在肿瘤内异质性。
同一患者的内镜活检标本与手术切除标本之间的PIK3CA突变状态高度一致，提示内镜活检标本可在临床上用于检测ESCC患者的PIK3CA突变。
