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Abstrak :
Latar Belakang : Melanoma malignum (MM) merupakan tumor ganas yang berasal dari proliferasi sel melanosit dan dapat ditemukan pada kulit, mukosa dan okular. Angka mortalitas MM cukup tinggi, terutama pada stadium lanjut yang ditandai dengan metastasis. Metastasis MM dipengaruhi berbagai faktor risiko yang dapat berbeda pada MM kulit, mukosa dan okular, salah satunya yaitu proses imunologi tumor yang dapat dinilai dari Tumor Infiltrating Lymphocyte (TIL). Komponen TIL yang berperan dalam proses penghindaran sistem imun pada MM adalah sel T regulator dengan penanda yang paling spesifik sampai saat ini adalah Foxp3. Hubungan Foxp3 dengan stadium MM masih kontroversial dan sampai saat ini belum ada penelitian mengenai hubungan Foxp3 pada TIL dengan stadium MM di Indonesia. Tujuan: Penelitian ini bertujuan untuk mengetahui hubungan karakteristik klinikopatologik dan ekspresi Foxp3 pada TIL dengan stadium MM. Metode: Penelitian analitik pada sediaan MM di Departemen Patologi Anatomik FKUI/RSCM selama periode Januari 2010 hingga Desember 2021. Pengambilan sampel penelitian dilakukan secara total sampling dari kasus yang memenuhi kriteria inklusi sesuai perhitungan besar sampel untuk masing-masing kelompok. Pemeriksaan imunohistokimia menggunakan antibodi primer monoklonal Foxp3. Data imunoekspresi dianalisis untuk mengetahui hubungannya dengan stadium MM. Hasil: Didapatkan 54 kasus MM, 19 kasus diantaranya merupakan MM kulit, 29 kasus MM okular, dan 6 kasus MM mukosa. Mayoritas kasus (63%) merupakan stadium lanjut. Tebal tumor dan mitosis berhubungan dengan stadium klinis MM kulit dan keseluruhan. Jenis kelamin perempuan, tebal tumor >2 mm, mitosis >16/10 LPB, adanya invasi limfovaskular dan invasi perineural umumnya mempunyai ekspresi Foxp3 yang rendah. Pada MM kulit dan MM keseluruhan, ekspresi Foxp3 yang rendah ditemukan pada stadium klinis lanjut meskipun tidak didapatkan hubungan yang signifikan. Kesimpulan: Tebal tumor dan mitosis berhubungan dengan stadium klinis MM kulit dan keseluruhan. Karakteristik klinikopatologik tidak berhubungan signifikan dengan ekspresi Foxp3 ......Background: Malignant melanoma (MM) is a malignant tumor originating from proliferation of melanocyte cells and can be found in skin, mucosa and ocular. The mortality rate for malignant melanoma is quite high, especially at advanced stage characterized by metastases. Various risk factors can predispose MM into metastases, which can be different in cutaneous, mucosal and ocular MM, one of which is the immunological process of the tumor which can be assessed from Tumor Infiltrating Lymphocyte (TIL). TIL components that play a role in the process of avoiding the immune system in malignant melanoma are regulatory T cells, whose the most specific marker so far is Foxp3. The association of Foxp3 with clinical stage of malignant melanoma is still controversial and until now there has been no research on the association of Foxp3 in TIL with clinical stage of MM in Indonesia. Aims: This study aims to determine the association between clinicopathological characteristics and Foxp3 expression in TIL with MM clinical stage. Methods: Analytic study on malignant melanoma diagnosed at Anatomical Pathology Department FKUI/RSCM during January 2010 until December 2021. Sampling was carried out by total sampling from cases that met the inclusion criteria according to the calculation of the sample size for each group. Immunohistochemical examination using Foxp3 monoclonal primary antibody. Immunoexpression data were analyzed to determine its relationship with clinical stage of malignant melanoma. Result: There were 54 cases of MM: 19 cases were skin MM, 29 cases of ocular MM, and 6 cases of mucosal MM. Majority of cases (63%) were in advanced stages. Tumor thickness and mitosis associated with clinical stage of cutaneous and overall MM. Female gender, tumor thickness >2 mm, mitoses >16/10 HPF, presence of lymphovascular invasion and perineural invasion generally had low Foxp3 expression. In cutaneous MM and overall MM, low Foxp3 expression was found at advanced clinical stage although no significant association was found. Conclusion: Tumor thickness and mitosis associated with clinical stage of cutaneous and overall MM. Clinicopathological characteristic was not statistically significant with Foxp3 expression. Low Foxp3 expression was associated with advanced clinical stage although no statistically significant association was found.

Abstrak :
Latar Belakang: Karsinoma nasofaring (KNF) adalah karsinoma yang berasal dari epitel permukaan nasofaring dengan angka insidensi yang tinggi di Tiongkok dan Asia Selatan. KNF masih menjadi masalah kesehatan di Indonesia dan prognosisnya dilaporkan buruk terkait dengan penanganan yang sering tidak optimal karena kebanyakan (60-95%) pasien berobat dalam stadium lanjut. Saat ini berkembang penelitian terhadap tumor microenvironment yang dapat dinilai melalui tumor infiltrating lympochyte (TIL) yang berkaitan dengan respons terapi pada beberapa tumor, termasuk KNF. Beberapa penelitian menyebutkan bahwa TIL salah satunya dapat dinilai dengan Foxp3. Foxp3 diketahui sebagai penanda sel T regulator (Treg) yang turut berperan dalam immunoregulator lingkungan sel-sel tumor dan dapat digunakan sebagai salah satu faktor prognosis. Hubungan antara ekspresi Foxp3 dengan respons terapi dapat dipertimbangkan menjadi salah satu faktor yang mempengaruhi prognosis KNF. Tujuan: Penelitian ini bertujuan untuk mengetahui hubungan antara ekspresi Foxp3 dengan respons terapi karsinoma nasofaring. Metode: Penelitian analitik dengan desain potong lintang pada sediaan KNF tidak berkeratin di Departemen Patologi Anatomik FKUI/RSCM selama periode Januari 2018 hingga Desember 2020. Pengambilan sampel penelitian dilakukan secara consecutive sampling dari kasus yang memenuhi kriteria inklusi dan eksklusi sesuai perhitungan besar sampel untuk masing-masing kelompok. Pemeriksaan imunohistokimia menggunakan antibodi primer monoklonal Foxp3. Data imunoekspresi dianalisis untuk mengetahui hubungannya dengan respons terapi karsinoma nasofaring. Hasil: Dari 60 kasus yang terdiagnosis KNF, sebanyak 40 kasus (66,7%) berjenis kelamin laki-laki dan 20 kasus lainnya (33,3%) berjenis kelamin perempuan dengan rasio 2:1. Terdapat perbedaan bermakna ekspresi Foxp3 intratumoral dengan respons terapi (p=0,01). Tidak terdapat perbedaan bermakna ekspresi Foxp3 peritumoral dengan respons terapi (p=0,114). Kesimpulan: Ekspresi Foxp3 mempunyai hubungan yang bermakna secara statistik dengan hasil evaluasi respons pasca kemoradiasi karsinoma nasofaring. ......Background: Nasopharyngeal carcinoma (NPC) is a carcinoma originating from the surface epithelium of the nasopharynx with a high incidence in Tiongkok and South Asia. NPC still become main health issue in Indonesia and the prognosis is reported to be poor due to suboptimal treatment because most of the patients (60-95%) are treated at an advanced stage. Currently, many research are developing on the tumor microenvironment that can be assessed by tumor infiltrating lymphochyte (TIL) which is associated with the treatment response in several tumors, including NPC. Some studies explore that TIL can be assessed with Foxp3. Foxp3 is known as a regulatory T cell (Treg) marker that plays a role in the immunoregulator environment of tumor cells and can be used as a prognostic factor. The relationship between Foxp3 expression and treatment response can be considered as one of the factors that influence the prognosis of NPC. Aims: This study aims to determine the relationship between Foxp3 expression and treatment response of NPC. Methods: An analytical study with a cross-sectional design on non-keratinizing NPC diagnosed at Anatomical Pathology Department of FKUI/RSCM during January 2018 until December 2020. The research sample was taken by consecutive sampling of cases that met the inclusion and did not include the exclusion criteria according to the calculation of the sample size for each group. Immunohistochemical examination using Foxp3 monoclonal antibody. Immunoexpression data were analyzed to determine its relationship with the treatment response of NPC. Results: From 60 selected cases diagnosed with NPC, there were consisted of 40 male patients (66,7%) and 20 female patients (33,3%) with ratio 2:1. There was a significant difference in intratumoral Foxp3 expression with treatment response (p=0.01). There was no significant difference in peritumoral Foxp3 expression with treatment response (p=0.114). Conclusion: Foxp3 expression had a statistically significant relationship with response therapy after chemoradiation.

Abstrak :
Latar belakang: kanker nasofaring (KNF) adalah keganasan yang umum dijumpai pada nasofaring. Cukup banyak bukti menunjukkan adanya keterkaitan KNF dengan sistem kekebalan tubuh. Tidak semua subset sel T merupakan sel T efektor. Sel T regulator (TReg) yang merupakan salah satu subset dari sel T, memiliki peran penting dalam mengatur imunitas anti tumor. Sampai saat ini belum dapat disimpulkan bahwa keberadaan sel TReg pada lokasi tumor pasti akan memicu pertumbuhan tumor. Akan tetapi, adanya sel T CD4+ dan CD8+ tentunya berpengaruh terhadap kontrol perkembangan tumor. Studi ini bertujuan untuk menilai karakterisitik CD4, CD8 dan FOXP3 pada pasien KNF dan hubungannya terhadap agresivitas tumor. Metode: penelitian ini merupakan studi kohort prospektif. Sel TReg dinilai menggunakan marker FOXP3. Jumlah protein CD4, CD8 dan FOXP3 pada jaringan biopsi tumor dideteksi dan diukur dengan ELISA. Volume tumor primer dan volume total metastasis kelenjar getah bening regional didapatkan dari proses delineasi dengan pencitraan 3D. Spearmen-rho test digunakan untuk menilai korelasi antara CD4, CD8 dan FOXP3 dengan volume tumor primer dan volume total metastasis kelenjar getah bening regional. Hasil: Sebanyak 23 subjek penelitian (14 pria dan 9 wanita) terkumpul berdasarkan kriteria inklusi dan eksklusi. Stadium KNF terbanyak pada studi ini adalah stadium IV (AJCC edisi ke-8). Analisis dengan uji Spearman menunjukkan korelasi kuat antara konsentrasi protein FOXP3 dan volume tumor primer (p=0.02, r=0.60), dan juga antara konsentrasi protein CD8 dan volume tumor primer (p=0.00, r=0.81). Menariknya, juga ditemukan korelasi antara konsentrasi CD8 dan FOXP3 (p=0.00, r=0.85). Tidak ditemukan korelasi antara konsentrasi protein CD4, CD8 dan FOXP3 dengan volume total metastasis kelenjar getah bening regional. Tidak ditemukan juga korelasi antara konsentrasi FOXP3 dan stadium KNF. Sayangnya, belum dapat disimpulkan hubungan antara konsentrasi FOXP3 dan respons terapi pada penelitian ini. Kesimpulan: Keberadaan sel TReg berpengaruh terhadap agresivitias lokal tumor yang ditandai dengan peningkatan volume massa tumor primer. Korelasi antar konsentrasi CD4, CD8 dan FOXP3 memberikan gambaran interaksi dan mekanisme respons imunitas tubuh dalam menjaga keseimbangan antara sel T efektor dan sel T regulator. ......Background: nasopharyngeal cancer (NPC) is a common malignancy found in the nasopharynx area. There is quite a lot of evidence showing a link between NPC and the immune system. Regulatory T cells (TReg), a subset of T cells, have an essential role in regulating anti-tumor immunity. It has not been confirmed that TReg cells at the tumor site will trigger tumor growth. However, the presence of CD4+ and CD8+ T cells certainly affects the control of tumor growth. This study aims to assess the characteristics of CD4, CD8, and FOXP3 in NPC patients and their relationship with tumor aggressiveness. Methods: a prospective cohort study was conducted on 23 subjects (14 men and 9 women) based on the inclusion and exclusion criteria. TReg cells were assessed using the FOXP3 marker. The number of CD4, CD8, and FOXP3 proteins in tumor biopsy tissue was detected and measured by ELISA kit (MBS2702975, MBS165145, MBS162054). The volume of the primary tumor and the total volume of regional lymph node metastases were obtained from the delineation process based on 3D imaging. Spearmen-rho test was used to assess the correlation of CD4, CD8, and FOXP3 with primary tumor volume and total volume of regional lymph node metastases. Results: A total of 23 study subjects (14 men and 9 women) were collected based on the inclusion and exclusion criteria. The most common NPC stage in this study was stage IV (AJCC 8th edition). Analysis by the Spearman-rho test showed a strong correlation between; concentration of FOXP3 protein and primary tumor volume (p=0.02, r=0.60) and the concentration of CD8 protein and primary tumor volume (p=0.00, r=0.81). Interestingly, a correlation was also found between the concentration of CD8 protein and FOXP3 (p=0.00, r=0.85). There was no correlation between CD4, CD8, and FOXP3 proteins and the total volume of regional lymph node metastases. There was also no correlation between FOXP3 concentration and NPC stage. Unfortunately, it is impossible to conclude the relationship between FOXP3 concentration and treatment response in this study. Conclusions: the presence of TReg cells affects the local aggressiveness of the tumor, which is characterized by an increase in the volume of the primary tumor. The correlation between CD4, CD8, and FOXP3 concentrations provides an overview of the interactions and mechanisms of the body's immune response to maintain a balance between effector T cells and regulatory T cells.