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"ABSTRAKIn the past 10 years, recent development of targeted therapy in metastatic renal cell carcinoma (mRCC) has provided a new hope and significantly enhanced the prognosis of the disease. Three class of targeted therapy were developed, including multi-targeted tyrosine kinase inhibitors (TKI), the mammalian target of rapamycin (mTOR) complex-1 kinase inhibitors, and the humanized antivascular endothelial growth factor (VEGF) monoclonal antibody. Hence, the objective of this article was to critically examine the current evidence of targeted therapy treatment for patients with mRCC. In the majority of trials evaluating targeted therapy, patients were stratified according to Memorial Sloan Kattering Cancer Center (MSKCC) risk model and the recommendation of targeted treatment based on risk features. In first-line setting (no previous treatment), sunitinib, pazopanib, or bevacizumab plus IFN-α were recommended as treatment options for patient with favorable- or intermediate- risk features and clear cell histology. Patients who progressed after previous cytokine therapy would have sorafenib or axitinib as treatment options. Clear-cell mRCC with favorable- or intermediate- risk features and failure with first-line TKI therapy might be treated with sorafenib, everolimus, temsirolimus or axitinib. However, the current evidence did not show the best treatment sequencing after first-line TKI failure. In patients with poor-risk clear-cell and non-clear cell mRCC, temsirolimus was the treatment option supported by phase III clinical trial. In addition, several new drugs, nowadays, are still being investigated and waiting for the result of phase II or III clinical trial, and this might change the standard therapy for mRCC in the future."

"ABSTRAKLatar belakang: Endometriosis merupakan kelainan ginekologik yang paling sering ditemukan. Seperti halnya endometrium di uterus juga dapat terjadi berbagai perubahan pada epitel yang melapisi kista endometriosis di ovarium, antara lain metaplasia, hiperplasia, atipia bahkan perubahan ke arah keganasan. Saat ini banyak penelitian yang menghubungkan antara endometriosis dan kanker ovarium terutama jenis clear cell dan dikenal dengan istilah endometriosis-associated ovarian carcinoma (EAOC) dan dilaporkan adanya mutasi yang menginaktifkan gen supresor tumor (ARID1A), sehingga protein BAF250a tidak diekpresikan pada Clear cell carcinoma (CCC) ovarii.Bahan dan cara: Dilakukan pulasan imunohistokimia ARID1A pada sampel 20 kasus endometriosis non atipik, 20 kasus atipik dan 20 kasus CCC ovarii tahun 2012 hingga Maret 2015. Dari kelompok kasus CCC didapatkan 9 kasus EAOC. Selanjutnya dilihat adakah perbedaan persentase ekspresi ARID1A pada endometriosis non atipik, atipik, CCC ovarii serta endometriosis disertai CCC (EAOC).Hasil: Pada kelompok kasus endometriosis non atipik, atipik dan CCC ada perbedaan bermakna persentase ekspresi ARID1A (uji Kruskal-Wallis p=0,0035). Selanjutnya dilakukan analisis Post Hoc uji Mann-Whitney dan didapatkan perbedaan bermakna persentase ekspresi ARID1A antara endometriosis non atipik dan atipik dengan CCC ovarii (p=0,001 dan p=0,0015). Pada kelompok kasus endometriosis non atipik, atipik dan endometriosis pada EAOC, didapatkan ada perbedaan bermakna persentase ekspresi ARID1A (Uji Kruskal-Walis p=0,011). Selanjutnya dilakukan analisis Post Hoc uji Mann-Whitney dan ada perbedaan bermakna persentase ekspresi ARID1A antara endometriosis non atipik dan atipik dengan EAOC (p=0,005 dan p=0,008).Kesimpulan: Ekspresi ARID1A pada endometriosis non atipik dan atipik lebih tinggi bermakna dibanding CCC ovarii dan EAOC. Sehingga ekspresi ARID1A kemungkinan dapat digunakan sebagai petanda adanya transformasi ganas pada endometriosis.

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ABSTRACT

Background: Endometriosis is one of the most common gynecological abnormalities found. Endometriosis cyst in the ovary also exhibited changes in epithelial cyst just like endometrium in the uterus. Changes in the epithelial cells also include metaplasia, hyperplasia, atyphia even changes toward malignan characteristics. Nowadays, there are some research that linked endometriosis and clear cell ovarian cancer which is known with endometriosis-associated ovarian carcinoma (EAOC) it is reported that there?s a mutation that activated tumor suppressor gene (ARID1A), so protein BAF250a is not expressed in Clear Cell Carcinoma (CCC) in the ovarium.

Materials and Methods: Immunohistochemistry staining of ARID1A were done in 20 samples of non-atypical endometriosis, 20 samples of atypical endometriosis, 20 samples of CCC in the ovarium from the year 2012 until march 2015. From the group that experienced CCC we get 9 cases of EAOC. After that, we see if there?s any difference in the percentage of ARID1A expression in non-atypical endometrosis, atypical endometriosis, CCC in the ovarium and endometriosis with CCC( EAOC).

Results: In non-atypical endometriosis, atypical and CCC cases groups there are significant differences on the percentage of ARID1A expression (Kruskal-Walis test p=0,0035). Post Hoc analysis were done using Mann-Whitney test and there are significant differences on ARID1A expression between non-atypical and atypical endometriosis with CCC (p=0,001 and p=0,0015). In non-atypical endometriosis, atypical and EAOC groups there are significant differences on the percentage of ARID1A expression (Kruskal-Walis test p=0,011). Post Hoc analysis were done using Mann-Whitney test and there are significant differences on ARID1A expression between non-atypical and atypical endometriosis with EAOC (p=0,005 and p=0,008).

Conclusion: Expression of ARID1A in non atypical and atypical endometriosis are significantly higher compared to ovarian CCC and EAOC. So, we can say that ARID1A may be used as a marker for malignancy transformation in endometriosis."

"ABSTRAK Latar belakang: Endometriosis merupakan kelainan ginekologik yang palingsering ditemukan. Seperti halnya endometrium di uterus juga dapat terjadiberbagai perubahan pada epitel yang melapisi kista endometriosis di ovarium,antara lain metaplasia, hiperplasia, atipia bahkan perubahan ke arah keganasan.Saat ini banyak penelitian yang menghubungkan antara endometriosis dan kankerovarium terutama jenis clear cell dan dikenal dengan istilah endometriosisassociatedovarian carcinoma (EAOC) dan dilaporkan adanya mutasi yangmenginaktifkan gen supresor tumor (ARID1A), sehingga protein BAF250a tidakdiekpresikan pada Clear cell carcinoma (CCC) ovarii.Bahan dan cara: Dilakukan pulasan imunohistokimia ARID1A pada sampel 20kasus endometriosis non atipik, 20 kasus atipik dan 20 kasus CCC ovarii tahun2012 hingga Maret 2015. Dari kelompok kasus CCC didapatkan 9 kasus EAOC.Selanjutnya dilihat adakah perbedaan persentase ekspresi ARID1A padaendometriosis non atipik, atipik, CCC ovarii serta endometriosis disertai CCC(EAOC).Hasil: Pada kelompok kasus endometriosis non atipik, atipik dan CCC adaperbedaan bermakna persentase ekspresi ARID1A (uji Kruskal-Wallis p=0,0035).Selanjutnya dilakukan analisis Post Hoc uji Mann-Whitney dan didapatkanperbedaan bermakna persentase ekspresi ARID1A antara endometriosis non atipikdan atipik dengan CCC ovarii (p=0,001 dan p=0,0015). Pada kelompok kasusendometriosis non atipik, atipik dan endometriosis pada EAOC, didapatkan adaperbedaan bermakna persentase ekspresi ARID1A (Uji Kruskal-Walis p=0,011).Selanjutnya dilakukan analisis Post Hoc uji Mann-Whitney dan ada perbedaanbermakna persentase ekspresi ARID1A antara endometriosis non atipik dan atipikdengan EAOC (p=0,005 dan p=0,008). Kesimpulan: Ekspresi ARID1A pada endometriosis non atipik dan atipik lebihtinggi bermakna dibanding CCC ovarii dan EAOC. Sehingga ekspresi ARID1Akemungkinan dapat digunakan sebagai petanda adanya transformasi ganas padaendometriosis.ABSTRACT Background: Endometriosis is one of the most common gynecologicalabnormalities found. Endometriosis cyst in the ovary also exhibited changes inepithelial cyst just like endometrium in the uterus. Changes in the epithelial cellsalso include metaplasia, hyperplasia, atyphia even changes toward malignancharacteristics. Nowadays, there are some research that linked endometriosis andclear cell ovarian cancer which is known with endometriosis-associated ovariancarcinoma (EAOC) it is reported that there?s a mutation that activated tumorsuppressor gene (ARID1A), so protein BAF250a is not expressed in Clear CellCarcinoma (CCC) in the ovarium.Materials and Methods: Immunohistochemistry staining of ARID1A were donein 20 samples of non-atypical endometriosis, 20 samples of atypicalendometriosis, 20 samples of CCC in the ovarium from the year 2012 until march2015. From the group that experienced CCC we get 9 cases of EAOC. After that,we see if there?s any difference in the percentage of ARID1A expression in nonatypicalendometrosis, atypical endometriosis, CCC in the ovarium andendometriosis with CCC( EAOC).Results: In non-atypical endometriosis, atypical and CCC cases groups there aresignificant differences on the percentage of ARID1A expression (Kruskal-Walistest p=0,0035). Post Hoc analysis were done using Mann-Whitney test and thereare significant differences on ARID1A expression between non-atypical andatypical endometriosis with CCC (p=0,001 and p=0,0015). In non-atypicalendometriosis, atypical and EAOC groups there are significant differences on thepercentage of ARID1A expression (Kruskal-Walis test p=0,011). Post Hocanalysis were done using Mann-Whitney test and there are significant differenceson ARID1A expression between non-atypical and atypical endometriosis withEAOC (p=0,005 and p=0,008).Conclusion: Expression of ARID1A in non atypical and atypical endometriosisare significantly higher compared to ovarian CCC and EAOC. So, we can say thatARID1A may be used as a marker for malignancy transformation inendometriosis.;Background: Endometriosis is one of the most common gynecologicalabnormalities found. Endometriosis cyst in the ovary also exhibited changes inepithelial cyst just like endometrium in the uterus. Changes in the epithelial cellsalso include metaplasia, hyperplasia, atyphia even changes toward malignancharacteristics. Nowadays, there are some research that linked endometriosis andclear cell ovarian cancer which is known with endometriosis-associated ovariancarcinoma (EAOC) it is reported that there?s a mutation that activated tumorsuppressor gene (ARID1A), so protein BAF250a is not expressed in Clear CellCarcinoma (CCC) in the ovarium.Materials and Methods: Immunohistochemistry staining of ARID1A were donein 20 samples of non-atypical endometriosis, 20 samples of atypicalendometriosis, 20 samples of CCC in the ovarium from the year 2012 until march2015. From the group that experienced CCC we get 9 cases of EAOC. After that,we see if there?s any difference in the percentage of ARID1A expression in nonatypicalendometrosis, atypical endometriosis, CCC in the ovarium andendometriosis with CCC( EAOC).Results: In non-atypical endometriosis, atypical and CCC cases groups there aresignificant differences on the percentage of ARID1A expression (Kruskal-Walistest p=0,0035). Post Hoc analysis were done using Mann-Whitney test and thereare significant differences on ARID1A expression between non-atypical andatypical endometriosis with CCC (p=0,001 and p=0,0015). In non-atypicalendometriosis, atypical and EAOC groups there are significant differences on thepercentage of ARID1A expression (Kruskal-Walis test p=0,011). Post Hocanalysis were done using Mann-Whitney test and there are significant differenceson ARID1A expression between non-atypical and atypical endometriosis withEAOC (p=0,005 and p=0,008).Conclusion: Expression of ARID1A in non atypical and atypical endometriosisare significantly higher compared to ovarian CCC and EAOC. So, we can say thatARID1A may be used as a marker for malignancy transformation inendometriosis.;Background: Endometriosis is one of the most common gynecologicalabnormalities found. Endometriosis cyst in the ovary also exhibited changes inepithelial cyst just like endometrium in the uterus. Changes in the epithelial cellsalso include metaplasia, hyperplasia, atyphia even changes toward malignancharacteristics. Nowadays, there are some research that linked endometriosis andclear cell ovarian cancer which is known with endometriosis-associated ovariancarcinoma (EAOC) it is reported that there?s a mutation that activated tumorsuppressor gene (ARID1A), so protein BAF250a is not expressed in Clear CellCarcinoma (CCC) in the ovarium.Materials and Methods: Immunohistochemistry staining of ARID1A were donein 20 samples of non-atypical endometriosis, 20 samples of atypicalendometriosis, 20 samples of CCC in the ovarium from the year 2012 until march2015. From the group that experienced CCC we get 9 cases of EAOC. After that,we see if there?s any difference in the percentage of ARID1A expression in nonatypicalendometrosis, atypical endometriosis, CCC in the ovarium andendometriosis with CCC( EAOC).Results: In non-atypical endometriosis, atypical and CCC cases groups there aresignificant differences on the percentage of ARID1A expression (Kruskal-Walistest p=0,0035). Post Hoc analysis were done using Mann-Whitney test and thereare significant differences on ARID1A expression between non-atypical andatypical endometriosis with CCC (p=0,001 and p=0,0015). In non-atypicalendometriosis, atypical and EAOC groups there are significant differences on thepercentage of ARID1A expression (Kruskal-Walis test p=0,011). Post Hocanalysis were done using Mann-Whitney test and there are significant differenceson ARID1A expression between non-atypical and atypical endometriosis withEAOC (p=0,005 and p=0,008).Conclusion: Expression of ARID1A in non atypical and atypical endometriosisare significantly higher compared to ovarian CCC and EAOC. So, we can say thatARID1A may be used as a marker for malignancy transformation inendometriosis.;Background: Endometriosis is one of the most common gynecologicalabnormalities found. Endometriosis cyst in the ovary also exhibited changes inepithelial cyst just like endometrium in the uterus. Changes in the epithelial cellsalso include metaplasia, hyperplasia, atyphia even changes toward malignancharacteristics. Nowadays, there are some research that linked endometriosis andclear cell ovarian cancer which is known with endometriosis-associated ovariancarcinoma (EAOC) it is reported that there?s a mutation that activated tumorsuppressor gene (ARID1A), so protein BAF250a is not expressed in Clear CellCarcinoma (CCC) in the ovarium.Materials and Methods: Immunohistochemistry staining of ARID1A were donein 20 samples of non-atypical endometriosis, 20 samples of atypicalendometriosis, 20 samples of CCC in the ovarium from the year 2012 until march2015. From the group that experienced CCC we get 9 cases of EAOC. After that,we see if there?s any difference in the percentage of ARID1A expression in nonatypicalendometrosis, atypical endometriosis, CCC in the ovarium andendometriosis with CCC( EAOC).Results: In non-atypical endometriosis, atypical and CCC cases groups there aresignificant differences on the percentage of ARID1A expression (Kruskal-Walistest p=0,0035). Post Hoc analysis were done using Mann-Whitney test and thereare significant differences on ARID1A expression between non-atypical andatypical endometriosis with CCC (p=0,001 and p=0,0015). In non-atypicalendometriosis, atypical and EAOC groups there are significant differences on thepercentage of ARID1A expression (Kruskal-Walis test p=0,011). Post Hocanalysis were done using Mann-Whitney test and there are significant differenceson ARID1A expression between non-atypical and atypical endometriosis withEAOC (p=0,005 and p=0,008).Conclusion: Expression of ARID1A in non atypical and atypical endometriosisare significantly higher compared to ovarian CCC and EAOC. So, we can say thatARID1A may be used as a marker for malignancy transformation inendometriosis."