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Abstrak :
ABSTRACT
We conducted this study to establish whether drinking alcohol alters the risk of early-onset colorectal cancer (CRC) in Japanese patients with Lynch syndrome (LS). The subjects were 66 LS patients with pathogenic mutation of mismatch repair genes (MLH1, MSH2, and MSH6) from the nationwide Japanese retrospective multicenter study. Cox proportional hazards modeling was used to investigate the factors correlating with early-onset CRC diagnosis, using clinical data such as gender, tobacco use, alcohol consumption, body mass index, gene mutation (MLH1, MSH2 vs MSH6), and family cancer history. Alcohol was significantly correlated with an increased risk of early-onset CRC [HR 2.44, 95% CI 1.13-5.16 (p = 0.02)], but tobacco use was not [HR 0.8, 95%CI 0.38-1.62 (p = 0.53)]. These findings suggest that alcohol consumption is correlated with an earlier onset of CRC in Japanese patients with LS.

Abstrak :

Gen mismatch repair (MMR) merupakan gen yang berperan dalam mekanisme DNA repair. Gen MMR dapat memperbaiki kesalahan pasangan basa, perubahan nukleotida dan kesalahan dalam unit pengulangan pasangan basa (microsatellites) selama proses replikasi DNA. Mutasi pada MMR yang umum terjadi pada gen MLH1 dan MSH2 memiliki asosiasi dengan terjadinya Lynch Syndrome pada pasien kanker kolon. Lynch Syndrome (LS) atau Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC) merupakan sindrom kanker kolon herediter yang paling umum diwariskan. LS dapat ditandai dengan mutasi gen MLH1 dan MSH2 berupa delesi dan duplikasi large genomic. Multiplex ligation-dependent probe amplification (MLPA) merupakan teknik kuantifikasi berbasis PCR yang dapat digunakan untuk mendeteksi perubahan copy number variant pada large genomic. Tujuan dari penelitian ini adalah untuk mengidentifikasi mutasi gen MLH1 dan MSH2 pada kanker kolon dengan teknik Multiplex Ligation-Dependent Probe Amplification (MLPA). Sebanyak 25 sampel darah pasien yang terdiagnosis kanker kolon yang dikumpulkan secara retrospektif di Rumah Sakit Kanker Dharmais dikoleksi dari tahun 2018-2019. Mutasi gen MLH1 dan MSH diidentifikasi pada sampel darah pasien yang terdiagnosis kanker kolon dengan teknik MLPA menggunakan Probemix P003-D1 MLH1/MSH2 (MRC-Holland). Penelitian ini berhasil melakukan optimalisasi penggunaan teknik MLPA dengan terpenuhinya kualitas fragmen kontrol MLPA, kualitas fragment analysis, dan comparative analysis pada perangkat lunak Coffalayser.Net. Hasil screening pada 25 sampel menunjukkan tidak ditemukan adanya pola mutasi gen MLH1 dan MSH2 pada sampel yang mengindikasikan tidak terjadinya Lynch Syndrome dan kanker kolon yang terjadi bersifat sporadis.

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Mismatch repair genes (MMR) plays a role in the mechanism of DNA repair. The MMR genes correct base pair errors, nucleotide changes, and errors in base pair repeating units (microsatellites) during DNA replication. Mutations in MMR are common in MLH1 and MSH2 genes that have an association with the occurrence of Lynch Syndrome in colon cancer. Lynch Syndrome or Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC) is the most common inherited hereditary colon cancer syndrome. LS is characterized by MLH1 and MSH2 gene mutations in the form of large genomic deletions and duplication. Multiplex ligation-dependent probe amplification (MLPA) is a PCRbased quantification technique that can detect changes in copy number variants in large genomics. The aim of the study was to identify MLH1 and MSH2 gene mutations in colon cancer with Multiplex Ligation-Dependent Probe Amplification (MLPA) technique. Twenty-five blood samples of patients diagnosed with colon cancer were collected in Dharmais Cancer Hospital collected in 2018-2019, retrospectively. Mutations in MLH1 and MSH2 genes were identified in blood samples of patients diagnosed with colon cancer by the MLPA technique using Probemix P003-D1 MLH1/MSH2 (MRC-Holland). This study succeeded in optimizing the use of MLPA technique by fulfilling the fragments quality control of MLPA, the quality of fragment analysis, and comparative analysis in Coffalayser.Net software. The results of 25 samples screening showed no pattern of MLH1 and MSH2 gene mutations in the sample. This data indicated that there was no Lynch Syndrome and the colon cancer was sporadic.

Abstrak :
ABSTRAK
Latar Belakang : Karsinoma kolorektal (KKR) merupakan penyebab kematian kedua di dunia dari seluruh jenis kanker. KKR dapat disebabkan oleh defek dari MMR DNA. Microsatellite instability (MSI) adalah penanda defek MMR DNA. KKR MSI-H memiliki gambaran karakteristik tertentu. Tumor-infiltrating-lymphocyte (TIL) merupakan faktor prognosis. Hilangnya ekspresi PMS2 dan MSH6 dapat sebagai penanda MSI. Penelitian ini bertujuan untuk menilai terjadinya MSI pada KKR di sisi kiri dan sisi kanan kolon melalui Hilangnya ekspresi PMS2 dan MSH6, serta mengetahui hubungan antara TIL dengan MSI-H. Bahan dan Metode : Dilakukan pulasan IHK PMS2 dan MSH6, serta penghitungan TIL. Penilaian dilakukan dengan menghitung hilangnya ekspresi PMS2 dan MSH6 pada inti sel dan dikelompokkan ke dalam kelompok mutasi dan tidak mutasi .Penghitungan TIL juga dikelompokkan ke dalam TIL tinggi dan rendah, berdasarkan nilai titik potong Hasil : Didapatkan 27,8% kasus menunjukkan hilangnya ekspresi PMS2 dan MSH6 dengan 14,4% kasus di distal kolon. TIL terbanyak di distal kolon 30% kasus. Tidak terdapat perbedaan bermakna antara mutasi PMS2 dan MSH6 dengan lokasi (p=0,829) dan TIL (p=0,187). Terdapat perbedaan bermakna antara usia dan lokasi (p=0,020) serta peningkatan ekspresi PMS2 dengan MSH6 (p=0,06). Kesimpulan : MSI-H ditemukan pada 27,8% kasus. Penggunaan PMS2 dan MSH6 pada penelitian ini belum dapat menggantikan 4 panel IHK. Terdapat kecenderungan dimana adenokarsinoma NOS memiliki frekuensi mutasi lebih tinggi dari adenokarsinoma musinosum. ABSTRACT
Background : Colorectal carcinoma (CRC) is the world second leading cause of death from all types of cancer. CRC can be caused by a defect of MMR DNA. Microsatellite instability (MSI) is a marker of DNA MMR defect. CRC MSI-H has a certain characteristic figures. Tumor-infiltrating lymphocytes (TIL) isone of prognostic factor. Loss expression of the PMS2 and MSH6 can be use as a marker of MSI. This study aims to assess the occurrence of MSI in CRC on the left side and the right side of the colon through the loss of expression of PMS2 and MSH6, and determine the relationship between TIL with MSI-H. Materials and Methods : Immunohistochemical staining using two marker, there is PMS2 and MSH6. We also counting the number of TIL. Assessment by calculating the loss expression of PMS2 and MSH6 in the cell nuclei and divided into two groups, the mutations and non mutations . TIL result also grouped into high and low, based on the cutoff point. Result : There are 27.8% of cases showed loss of expression of PMS 2 and MSH6 with 14.4% of cases in the distal colon. About 30% TIL cases located in distal colon. There were no significant differences between PMS2 and MSH6 mutation with the location (p = 0.829) and TIL (p = 0.187). There are significant differences between age and location (p = 0.020) and increased expression of PMS2 with MSH6 (p = 0.06). \ Conclusion : MSI-H was found in 27.8% of cases. The use of PMS2 and MSH6 in this study have not been able to replace 4 panels of IHC. There is a tendency where the adenocarcinoma NOS have a higher mutation frequency than mucinous adenocarcinoma. ;Background : Colorectal carcinoma (CRC) is the world second leading cause of death from all types of cancer. CRC can be caused by a defect of MMR DNA. Microsatellite instability (MSI) is a marker of DNA MMR defect. CRC MSI-H has a certain characteristic figures. Tumor-infiltrating lymphocytes (TIL) isone of prognostic factor. Loss expression of the PMS2 and MSH6 can be use as a marker of MSI. This study aims to assess the occurrence of MSI in CRC on the left side and the right side of the colon through the loss of expression of PMS2 and MSH6, and determine the relationship between TIL with MSI-H. Materials and Methods : Immunohistochemical staining using two marker, there is PMS2 and MSH6. We also counting the number of TIL. Assessment by calculating the loss expression of PMS2 and MSH6 in the cell nuclei and divided into two groups, the mutations and non mutations . TIL result also grouped into high and low, based on the cutoff point. Result : There are 27.8% of cases showed loss of expression of PMS 2 and MSH6 with 14.4% of cases in the distal colon. About 30% TIL cases located in distal colon. There were no significant differences between PMS2 and MSH6 mutation with the location (p = 0.829) and TIL (p = 0.187). There are significant differences between age and location (p = 0.020) and increased expression of PMS2 with MSH6 (p = 0.06). \ Conclusion : MSI-H was found in 27.8% of cases. The use of PMS2 and MSH6 in this study have not been able to replace 4 panels of IHC. There is a tendency where the adenocarcinoma NOS have a higher mutation frequency than mucinous adenocarcinoma. ;Background : Colorectal carcinoma (CRC) is the world second leading cause of death from all types of cancer. CRC can be caused by a defect of MMR DNA. Microsatellite instability (MSI) is a marker of DNA MMR defect. CRC MSI-H has a certain characteristic figures. Tumor-infiltrating lymphocytes (TIL) isone of prognostic factor. Loss expression of the PMS2 and MSH6 can be use as a marker of MSI. This study aims to assess the occurrence of MSI in CRC on the left side and the right side of the colon through the loss of expression of PMS2 and MSH6, and determine the relationship between TIL with MSI-H. Materials and Methods : Immunohistochemical staining using two marker, there is PMS2 and MSH6. We also counting the number of TIL. Assessment by calculating the loss expression of PMS2 and MSH6 in the cell nuclei and divided into two groups, the mutations and non mutations . TIL result also grouped into high and low, based on the cutoff point. Result : There are 27.8% of cases showed loss of expression of PMS 2 and MSH6 with 14.4% of cases in the distal colon. About 30% TIL cases located in distal colon. There were no significant differences between PMS2 and MSH6 mutation with the location (p = 0.829) and TIL (p = 0.187). There are significant differences between age and location (p = 0.020) and increased expression of PMS2 with MSH6 (p = 0.06). \ Conclusion : MSI-H was found in 27.8% of cases. The use of PMS2 and MSH6 in this study have not been able to replace 4 panels of IHC. There is a tendency where the adenocarcinoma NOS have a higher mutation frequency than mucinous adenocarcinoma.