结直肠癌患者中林奇综合征的高概率与KRAS和PIK3CA突变的更高发生率相关。

High Probability of Lynch Syndrome Among Colorectal Cancer Patients Is Associated With Higher Occurrence of KRAS and PIK3CA Mutations.

作者信息

Heriyanto Didik Setyo, Yoshuantari Naomi, Akbariani Gilang, Lau Vincent, Hanini Hanifa, Hidayati Zulfa, Arief Muhammad Zulfikar, Gunawan Andrew Nobiantoro, Ridwanuloh Asep Muhamad, Kusharyoto Wien, Handaya Adeodatus Yuda, Ilyas Mohammad, Kurnianda Johan, Hutajulu Susanna Hilda, Susanti Susanti

机构信息

Department of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr Sardjito General Hospital Yogyakarta, Indonesia.

Collaboration Research Center for Precision Oncology based Omics - PKR PrOmics, Yogyakarta, Indonesia.

出版信息

World J Oncol. 2024 Aug;15(4):612-624. doi: 10.14740/wjon1843. Epub 2024 Jun 17.

DOI:10.14740/wjon1843

PMID:38993255

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11236368/

Abstract

BACKGROUND

In Indonesia, early-onset colorectal cancer (EOCRC) rates are higher in patients < 50 years old compared to Western populations, possibly due to a higher frequency of Lynch syndrome (LS) in CRC patients. We aimed to examine the association of KRAS and PIK3CA mutations with LS.

METHODS

In this retrospective cross-sectional single-center study, the PCR-HRM-based test was used for screening of microsatellite instability (MSI) mononucleotide markers (BAT25, BAT26, BCAT25, MYB, EWSR1), MLH1 promoter methylation, and oncogene mutations of BRAF (V600E), KRAS (exon 2 and 3), and PIK3CA (exon 9 and 20) in FFPE DNA samples.

RESULTS

All the samples (n = 244) were from Dr. Sardjito General Hospital Yogyakarta, Indonesia. KRAS and PIK3CA mutations were found in 151/244 (61.88%) and 107/244 (43.85%) of samples, respectively. KRAS and PIK3CA mutations were significantly associated with MSI status in 32/42 (76.19%) and 25/42 (59.52%) of samples, respectively. KRAS mutation was significantly associated with LS status in 26/32 (81.25%) of samples. The PIK3CA mutation was present in a higher proportion in LS samples of 19/32 (59.38%), but not statistically significant. Clinicopathology showed that KRAS mutation was significantly associated with right-sided CRC and higher histology grade in 39/151 (25.83%) and 24/151 (16.44%) samples, respectively. PIK3CA mutation was significantly associated with female sex and lower levels of tumor-infiltrating lymphocytes in 62/107 (57.94%) and 26/107 (30.23%) samples, respectively. KRAS and PIK3CA mutations did not significantly affect overall survival (120 months) in LS and non-LS patients.

CONCLUSIONS

The high probability of LS in Indonesian CRC patients is associated with KRAS and PIK3CA mutations.

摘要

背景

在印度尼西亚，与西方人群相比，50岁以下患者的早发性结直肠癌（EOCRC）发病率更高，这可能是由于结直肠癌患者中林奇综合征（LS）的发生率较高。我们旨在研究KRAS和PIK3CA突变与LS的关联。

方法

在这项回顾性横断面单中心研究中，基于PCR-HRM的检测用于筛查福尔马林固定石蜡包埋（FFPE）DNA样本中的微卫星不稳定性（MSI）单核苷酸标记（BAT25、BAT26、BCAT25、MYB、EWSR1）、MLH1启动子甲基化以及BRAF（V600E）、KRAS（第2和3外显子）和PIK3CA（第9和20外显子）的癌基因突变。

结果

所有样本（n = 244）均来自印度尼西亚日惹市的萨迪托综合医院。分别在151/244（61.88%）和107/244（43.85%）的样本中发现了KRAS和PIK3CA突变。KRAS和PIK3CA突变分别在32/42（76.19%）和25/42（59.52%）的样本中与MSI状态显著相关。KRAS突变在26/32（81.25%）的样本中与LS状态显著相关。PIK3CA突变在19/32（59.38%）的LS样本中比例较高，但无统计学意义。临床病理显示，KRAS突变分别在39/151（25.83%）和24/151（16.44%）的样本中与右侧结直肠癌和更高的组织学分级显著相关。PIK3CA突变分别在62/107（57.94%）和26/107（30.23%）的样本中与女性性别和较低水平的肿瘤浸润淋巴细胞显著相关。KRAS和PIK3CA突变对LS和非LS患者的总生存期（120个月）无显著影响。