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

IF 2.1 Q3 ONCOLOGY World Journal of Oncology Pub Date : 2024-08-01 Epub Date: 2024-06-17 DOI:10.14740/wjon1843

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

{"title":"High Probability of Lynch Syndrome Among Colorectal Cancer Patients Is Associated With Higher Occurrence of KRAS and PIK3CA Mutations.","authors":"Didik Setyo Heriyanto, Naomi Yoshuantari, Gilang Akbariani, Vincent Lau, Hanifa Hanini, Zulfa Hidayati, Muhammad Zulfikar Arief, Andrew Nobiantoro Gunawan, Asep Muhamad Ridwanuloh, Wien Kusharyoto, Adeodatus Yuda Handaya, Mohammad Ilyas, Johan Kurnianda, Susanna Hilda Hutajulu, Susanti Susanti","doi":"10.14740/wjon1843","DOIUrl":null,"url":null,"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.","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236368/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14740/wjon1843","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/17 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

结直肠癌患者中林奇综合征的高概率与 KRAS 和 PIK3CA 基因突变的高发生率有关。

背景：在印度尼西亚，与西方人群相比，50岁以下患者的早发结直肠癌（EOCRC）发病率较高，这可能是由于CRC患者中林奇综合征（LS）的发病率较高。我们的目的是研究 KRAS 和 PIK3CA 突变与 LS 的关系：在这项回顾性横断面单中心研究中，我们使用基于 PCR-HRM 的检测方法筛查了 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（2 号外显子和 3 号外显子）和 PIK3CA（9 号外显子和 20 号外显子）的癌基因突变：所有样本（n = 244）均来自印度尼西亚日惹的萨吉托博士综合医院（Dr. Sardjito General Hospital Yogyakarta）。在151/244（61.88%）和107/244（43.85%）份样本中分别发现了KRAS和PIK3CA突变。在32/42（76.19%）和25/42（59.52%）的样本中，KRAS和PIK3CA突变分别与MSI状态显著相关。在26/32（81.25%）的样本中，KRAS突变与LS状态明显相关。PIK3CA突变在LS样本中的比例较高，为19/32（59.38%），但无统计学意义。临床病理学显示，在 39/151 例（25.83%）和 24/151 例（16.44%）样本中，KRAS 突变与右侧 CRC 和组织学分级较高明显相关。在62/107（57.94%）和26/107（30.23%）个样本中，PIK3CA突变分别与女性性别和较低的肿瘤浸润淋巴细胞水平明显相关。KRAS和PIK3CA突变对LS和非LS患者的总生存期（120个月）没有明显影响：结论：印尼 CRC 患者 LS 的高概率与 KRAS 和 PIK3CA 突变有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

World Journal of Oncology ONCOLOGY-

CiteScore

6.10

自引率

15.40%

发文量

期刊介绍： World Journal of Oncology, bimonthly, publishes original contributions describing basic research and clinical investigation of cancer, on the cellular, molecular, prevention, diagnosis, therapy and prognosis aspects. The submissions can be basic research or clinical investigation oriented. This journal welcomes those submissions focused on the clinical trials of new treatment modalities for cancer, and those submissions focused on molecular or cellular research of the oncology pathogenesis. Case reports submitted for consideration of publication should explore either a novel genomic event/description or a new safety signal from an oncolytic agent. The areas of interested manuscripts are these disciplines: tumor immunology and immunotherapy; cancer molecular pharmacology and chemotherapy; drug sensitivity and resistance; cancer epidemiology; clinical trials; cancer pathology; radiobiology and radiation oncology; solid tumor oncology; hematological malignancies; surgical oncology; pediatric oncology; molecular oncology and cancer genes; gene therapy; cancer endocrinology; cancer metastasis; prevention and diagnosis of cancer; other cancer related subjects. The types of manuscripts accepted are original article, review, editorial, short communication, case report, letter to the editor, book review.