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"Kaitannya dengan ekspresi protein MLH1, MSH2, dan SMAD4, dan membandingkannya dengan pasien kanker kolorektal usia di atas 60 tahun.Metode: Data rekam medis pasien kanker kolorektal usia di bawah 40 tahun dan usia di atas 60 tahun , dikumpulkan dari 3 rumah sakit: Jakarta, Makasar, dan Bandung. Kelompok etnis dipilih dari suku bangsa Jawa, Makasar (Sulawesi Selatan, dan Minangkabau (Sumatera Barat) yang dikonfirmasi berdasarkan kuesioner. Pada spesimen tumor dilakukan pemeriksaan histopatologi, gradasi tumor, serta pemeriksaan imunohistokimia untuk penentuan ekspresi protein MLH1 dan MSH2 untuk menilai mutasi instabilitas mikrosatelit. Ekspresi protein SMAD4 diperiksa untuk memastikan bahwa jaringan tumor tidak berasal dari instabilitas mikrosatelit.Hasil: Telah dikumpulkan 121 penderita kanker kolorektal dari etnis Sunda, Jawa, Makasar, dan Minangkabau. Derajad keganasan antara pasien muda dan pasien tua berbeda secara bermakna (p = 0.001). Pewarnaan imunohistokimia untuk protein MSH2 dan MLH1 yang dilakukan pada masing-masing 92 dan 97 pasien, menunjukkan tidak terdapat perbedaan bermakna dalam hal ekspresi MLH1 dan MSH2 dan gradasi tumor, yang berarti tidak ada hubungan antara instabilitas mikrosatelit dan derajad tumor.Kesimpulan: Karakter kliniko patologi kanker kolorektal pada penduduk asli Indonesia, tidak berbeda antara pasien usia muda (< 40 tahun) dan pasien usia tua (>60 tahun) pada kelompok etnis yang sama. Juga tidak terdapat perbedaan dalam ekspresi protein MSH2 dan MLH1, yang merupakan indikator instabilitas mikrosatelit.

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Aim: To obtain clinicopathological characteristics of colorectal cancer among young native Indonesians and to assess MLH1, MSH2, and SMAD4 protein expressions, comparing them with a matched population of colorectal cancer patients aged 60 years old and older.

Methods: Medical records of colorectal cancer patients aged 40 years or younger and 60 years or older from several hospitals in three Indonesian cities ? Jakarta, Makassar, and Bandung - were reviewed. The ?native? ethnic groups were selected from those originating from Java, Makassar (South Celebes), Miinangkabau (West Sumatra). Ethnicity of 121 colorectal carcinoma patients was confirmed by fulfilling requirements in a questionnaire. Tumor specimens of those patients underwent evaluation for histopathology, tumor grading as well as immunohistochemical analysis to assess MLH1, MSH2 protein expressions to detect microsatellite instability mutation pathway and SMAD4 protein expression to reconfirm that the specimens were not microsatellite instability origin.

Results: There were 121 colorectal carcinoma cases of Sundanese, Javanese, Macassarese and Minangkabau ethnic group. This study indicated that colorectal cancer has statistically different grade (p = 0.001) between the young and the older patients. Immunohistochemical staining for MSH2 protein and MLH1 were done for 92 and 97 specimens respectively. There was no significant difference between the expressions of MLH1 and MSH2 on tumor grading, indicated there was no correlation between microsatellite instability and tumor grading in this study.

Conclusion: Colorectal cancer in young native Indonesian patients (40 years old or less) was not different in clinicopathological characteristics compared to older patients (60 years old or more) in similar ethnic groups. There was also no difference in MSH2 and MLH1 protein expressions, important indicators of microsatellite instability."

"ABSTRAK Latar Belakang :Karsinoma kolorektal (KKR) merupakan penyebab kematian kedua di dunia dari seluruh jeniskanker. 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 danMSH6 dapat sebagai penanda MSI. Penelitian ini bertujuan untuk menilai terjadinya MSI padaKKR di sisi kiri dan sisi kanan kolon melalui Hilangnya ekspresi PMS2 dan MSH6, sertamengetahui hubungan antara TIL dengan MSI-H.Bahan dan Metode :Dilakukan pulasan IHK PMS2 dan MSH6, serta penghitungan TIL. Penilaian dilakukan denganmenghitung hilangnya ekspresi PMS2 dan MSH6 pada inti sel dan dikelompokkan ke dalamkelompok mutasi dan tidak mutasi .Penghitungan TIL juga dikelompokkan ke dalam TIL tinggidan 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 perbedaanbermakna antara mutasi PMS2 dan MSH6 dengan lokasi (p=0,829) dan TIL (p=0,187). Terdapatperbedaan bermakna antara usia dan lokasi (p=0,020) serta peningkatan ekspresi PMS2 denganMSH6 (p=0,06).Kesimpulan :MSI-H ditemukan pada 27,8% kasus. Penggunaan PMS2 dan MSH6 pada penelitian ini belumdapat menggantikan 4 panel IHK. Terdapat kecenderungan dimana adenokarsinoma NOSmemiliki 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 ofDNA MMR defect. CRC MSI-H has a certain characteristic figures. Tumor-infiltratinglymphocytes (TIL) isone of prognostic factor. Loss expression of the PMS2 and MSH6 can beuse as a marker of MSI. This study aims to assess the occurrence of MSI in CRC on the left sideand the right side of the colon through the loss of expression of PMS2 and MSH6, anddetermine the relationship between TIL with MSI-H. Materials and Methods :Immunohistochemical staining using two marker, there is PMS2 and MSH6. We also countingthe number of TIL. Assessment by calculating the loss expression of PMS2 and MSH6 in the cellnuclei and divided into two groups, the mutations and non mutations . TIL result also groupedinto 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 inthe distal colon. About 30% TIL cases located in distal colon. There were no significantdifferences 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 increasedexpression 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 beenable to replace 4 panels of IHC. There is a tendency where the adenocarcinoma NOS have ahigher 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 ofDNA MMR defect. CRC MSI-H has a certain characteristic figures. Tumor-infiltratinglymphocytes (TIL) isone of prognostic factor. Loss expression of the PMS2 and MSH6 can beuse as a marker of MSI. This study aims to assess the occurrence of MSI in CRC on the left sideand the right side of the colon through the loss of expression of PMS2 and MSH6, anddetermine the relationship between TIL with MSI-H. Materials and Methods :Immunohistochemical staining using two marker, there is PMS2 and MSH6. We also countingthe number of TIL. Assessment by calculating the loss expression of PMS2 and MSH6 in the cellnuclei and divided into two groups, the mutations and non mutations . TIL result also groupedinto 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 inthe distal colon. About 30% TIL cases located in distal colon. There were no significantdifferences 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 increasedexpression 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 beenable to replace 4 panels of IHC. There is a tendency where the adenocarcinoma NOS have ahigher 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 ofDNA MMR defect. CRC MSI-H has a certain characteristic figures. Tumor-infiltratinglymphocytes (TIL) isone of prognostic factor. Loss expression of the PMS2 and MSH6 can beuse as a marker of MSI. This study aims to assess the occurrence of MSI in CRC on the left sideand the right side of the colon through the loss of expression of PMS2 and MSH6, anddetermine the relationship between TIL with MSI-H. Materials and Methods :Immunohistochemical staining using two marker, there is PMS2 and MSH6. We also countingthe number of TIL. Assessment by calculating the loss expression of PMS2 and MSH6 in the cellnuclei and divided into two groups, the mutations and non mutations . TIL result also groupedinto 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 inthe distal colon. About 30% TIL cases located in distal colon. There were no significantdifferences 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 increasedexpression 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 beenable to replace 4 panels of IHC. There is a tendency where the adenocarcinoma NOS have ahigher mutation frequency than mucinous adenocarcinoma. "

"ABSTRAK Latar Belakang: Prognosis dan tatalaksana kanker kolorektal sangat dipengaruhi olehstadiumnya. Pada tahun 2012, the European Society for Medical Oncology mempublikasikan pedoman yang menyarankan evaluasi terhadap microsatellite instability MSI untuk menentukan perjalanan penyakit kanker kolorektal. Penelitian ini bertujuan untuk menginvestigasi faktor prognostik MSI-H pada kadar kesintasan 3 tahun. Metode: Penelitian ini menggunakan data sekunder dari penelitian sebelumnya oleh Setyaningsih, dkk. yang berjudul ldquo;Penelitian Microsattelite Instability Melalui Ekspresi PMS2 dan MSH6 serta Tumor-Infiltrating Lymphocyte pada Kanker Kolorektal Kiri dan Kanan rdquo;. Kami memasukkan total 90 pasien yang didiagnosis sebagai kanker kolorektal yang menjalani bedah reseksi dari tahun 2008 hingga 2013 di RSUPN Cipto Mangunkusumo. Kami menganalisa status MSI sebagai faktor prognosis untuk menentukan kadar kesintasan 3 tahun yang disesuaikan dengan ukuran dan tipe tumor, metastasis, dan umur pasien. Hasil: Dari 90 pasien, 47 orang dapat dilakukan follow up. Mayoritas pasien didiagnosis dengan kanker kolorektal stadium III n=29; 61,7 , 8 pasien didiagnosis sebagai stadium IV, 9 pasien didiagnsosis sebagai stadium II, dan 1 pasien didiagnosis dengan stadidum I. Kesintasan tiga tahun untuk pasien MSI-H adalah 33,3 , 22,2 , dan 20 untuk stadium II, III, dan IV; dibandingkan dengan kesintasan tiga tahun untuk pasien MSI-L yaitu 0 , 5 , dan 0 p = 0,003 . Selain itu, berdasarkan analisis multivariate, kami menemukan bahwa MSI-L memiliki hazard ratio 2,421 1,991-2,851 dibandingkan dengan MSI-H p = 0,004 . Kesimpulan: MSI-H adalah faktor prognosis yang penting untuk menentukan kesintasan tiga tahun pada pasien kanker kolorektal. Kami menemukan bahwa pasien dengan MSI-H memiliki prognosis yang lebih baik dibandingkan dengan pasien MSI-L. Temuan ini sejalan dengan pedoman dan penelitian sebelumnya yang menyarankan penggunaan MSI untuk menentukan perjalanan penyakit dan pilihan terapi pada pasien kanker kolorektal.

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ABSTRACT Background The prognosis and treatment of colorectal cancer is based on its stadium. Due to its features, the prognosis stage II colorectal cancer is still considered inexact with the survival rates ranging from 87,5 in stage IIA to 58.4 in stage IIC.The European Society for Medical Oncology published a guideline in 2012 which suggests that microsatellite instability MSI should be evaluated to determine the course of the colorectal cancer. This study is aimed to investigate prognostic factor of MSI ndash H for 3 years survival rates. Method This study used secondary data from a previous study performed by Setyaningsih, et al. titled ldquo Penelitian Microsattelite Instability Melalui Ekspresi PMS2 dan MSH6 serta Tumor Infiltrating Lymphocyte pada Kanker Kolorektal Kiri dan Kanan rdquo . We included a total of 90 patients diagnosed with colorectal cancer who underwent resection surgery from 2008 to 2013 in RSUPN Cipto Mangunkusumo. We analyzed the MSI status as a prognosticfactor to determine 3 years survival rate, adjusted with the size and types of the tumor, metastasis, and age. Results Among 90 patients, 47 have been followed up. The median age was 47 years. The majority of the patients was diagnosed with stage III colorectal cancer n 29 61.7 , 8 patients were diagnosed with stage IV, 9 patients were diagnosed with stage II colorectal cancer, and 1 patient was diagnosed with stage I colorectal cancer. Three years survival rates for patients with MSI H are 33.3 , 22.2 , and 20 for stage II, III, and IV respectively, compared to 5 years survical rates for MSI L patients which are 0 , 5 , and 0 p 0.003 . Futhermore, with multivariate analysis, we found that MSI L has 2.421 1.991 2.851 hazard ratio compared to MSI H p 0.004 . Conclusions MSI H is an important prognostic factor to determine 3 years survival rate in colorectal cancer patients.We found that patient with MSI H have more favourable prognosis compared to MSI L patients This findings complements previous guidelines and studies which suggested the use of MSI to determine the disease course and treatment options in colorectal cancer."