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

Autor:	Heriyanto DS; 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., Yoshuantari N; Department of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr Sardjito General Hospital Yogyakarta, Indonesia., Akbariani G; Pathgen Diagnostik Teknologi, Ir. Soekarno Science and Technology Park, National Research and Innovation Agency Republic of Indonesia, Bogor, Indonesia., Lau V; Department of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr Sardjito General Hospital Yogyakarta, Indonesia., Hanini H; Pathgen Diagnostik Teknologi, Ir. Soekarno Science and Technology Park, National Research and Innovation Agency Republic of Indonesia, Bogor, Indonesia., Hidayati Z; Pathgen Diagnostik Teknologi, Ir. Soekarno Science and Technology Park, National Research and Innovation Agency Republic of Indonesia, Bogor, Indonesia., Arief MZ; Pathgen Diagnostik Teknologi, Ir. Soekarno Science and Technology Park, National Research and Innovation Agency Republic of Indonesia, Bogor, Indonesia., Gunawan AN; Department of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr Sardjito General Hospital Yogyakarta, Indonesia., Ridwanuloh AM; Research Center for Genetic Engineering, Research Organization for Life Sciences and Environment, National Research and Innovation Agency Republic of Indonesia, Ir. Soekarno Science and Technology Park, Bogor, Indonesia., Kusharyoto W; Research Center for Genetic Engineering, Research Organization for Life Sciences and Environment, National Research and Innovation Agency Republic of Indonesia, Ir. Soekarno Science and Technology Park, Bogor, Indonesia., Handaya AY; Division of Digestive Surgeon, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr Sardjito General Hospital Yogyakarta, Indonesia., Ilyas M; Molecular Pathology Research Group, Academic Unit of Translational Medical Science, Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham, UK., Kurnianda J; Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr Sardjito General Hospital, Yogyakarta, Indonesia., Hutajulu SH; Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr Sardjito General Hospital, Yogyakarta, Indonesia., Susanti S; Pathgen Diagnostik Teknologi, Ir. Soekarno Science and Technology Park, National Research and Innovation Agency Republic of Indonesia, Bogor, Indonesia.; Molecular Pathology Research Group, Academic Unit of Translational Medical Science, Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham, UK.; Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Muhammadiyah Purwokerto, Indonesia.
Jazyk:	angličtina
Zdroj:	World journal of oncology [World J Oncol] 2024 Aug; Vol. 15 (4), pp. 612-624. Date of Electronic Publication: 2024 Jun 17.
DOI:	10.14740/wjon1843
Abstrakt:	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. Competing Interests: MI was appointed as specialist committee member to the Diagnostics Assessment Committee of the National Institute for Health and Care Excellence (NICE), which produced the guidance DG27 on Lynch Syndrome testing. DSH, AMR, and MI are unpaid scientific advisors of PathGen Diagnostik Teknologi. Other authors have no competing interest to declare. (Copyright 2024, Heriyanto et al.)
Databáze:	MEDLINE
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