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胃癌中的PIK3CA突变以及微卫星不稳定性状态在PIK3CA基因第9和20外显子突变中的作用。

PIK3CA mutation in gastric cancer and the role of microsatellite instability status in mutations of exons 9 and 20 of the PIK3CA gene.

作者信息

Polom Karol, Marrelli Daniele, Roviello Giandomenico, Pascale Valeria, Voglino Costantino, Vindigni Carla, Generali Daniele, Roviello Franco

机构信息

Unit of General Surgery and Surgical Oncology, University of Siena, Italy.

Department of Surgical Oncology, Medical University of Gdansk, Poland.

出版信息

Adv Clin Exp Med. 2018 Jul;27(7):963-969. doi: 10.17219/acem/70795.

Abstract

BACKGROUND

A better understanding of molecular gastric cancer (GC) entities may help in tailored treatments of that neoplasm. The PIK3CA mutation is one of the most important in many cancers.

OBJECTIVES

We performed a comparison of clinical and pathological data of the PIK3CA mutation in GC patients.

MATERIAL AND METHODS

The analysis was done on 472 patients operated on in 1 center. Polymerase chain reaction (PCR) was used for the screening of PIK3CA (exon 9 and 20). For microsatellite instability (MSI) we used 5 quasi-monomorphic mononucleotide repeats - BAT-26, BAT-25, NR-24, NR-21, and NR-27. The clinical and pathological data was analyzed.

RESULTS

PIK3CA mutation was observed in 10 out of 472 GC patients (2.1%). Nine out of 10 were MSI (9 of 111 MSI patients - 8.1%). Half of the 10 patients had mutations in exon 9 and the other half in exon 20. A majority of patients with the PIK3CA mutation had MSI (p < 0.001). The 5-year survival of MSI patients with the PIK3CA mutation was 40% and without the mutation, 70.4% (p = 0.309). For patients with the mutation in exon 9, the 5-year survival was 0%, and for those with the mutation in exon 20, 80% (p = 0.031). The Cox proportional hazards regression analysis did not show that PIK3CA is statistically correlated with a worse overall survival.

CONCLUSIONS

PIK3CA mutation in GC is a rare finding. It is strongly associated with the MSI molecular subgroup, presenting a worse outcome than other MSI patients. A completely different outcome is associated with the mutation in exon 9 compared to the mutation in exon 20, with the latter being more favorable.

摘要

背景

更好地了解分子型胃癌实体可能有助于对该肿瘤进行个性化治疗。PIK3CA突变是许多癌症中最重要的突变之一。

目的

我们对胃癌患者中PIK3CA突变的临床和病理数据进行了比较。

材料与方法

对在1个中心接受手术的472例患者进行分析。采用聚合酶链反应(PCR)筛选PIK3CA(第9和20外显子)。对于微卫星不稳定性(MSI),我们使用了5个准单态单核苷酸重复序列——BAT-26、BAT-25、NR-24、NR-21和NR-27。对临床和病理数据进行分析。

结果

472例胃癌患者中有10例(2.1%)检测到PIK3CA突变。10例中有9例为MSI(111例MSI患者中的9例——8.1%)。10例患者中有一半第9外显子发生突变,另一半第20外显子发生突变。大多数PIK3CA突变患者为MSI(p<0.001)。PIK3CA突变的MSI患者5年生存率为40%,未发生突变的患者为70.4%(p=0.309)。第9外显子发生突变的患者5年生存率为0%,第20外显子发生突变的患者为80%(p=0.031)。Cox比例风险回归分析未显示PIK3CA与总体生存率较差存在统计学相关性。

结论

胃癌中的PIK3CA突变是一个罕见的发现。它与MSI分子亚组密切相关,其预后比其他MSI患者更差。与第20外显子突变相比,第9外显子突变的预后完全不同,后者更有利。

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