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"Pendahuluan: Proses karsinogenesis adenokarsinoma prostat terjadi akibat disregulasi kadar zinc dalam sel. Molekul zinc intrasel berperan dalam metabolisme aerob mitokondria dan induksi apoptosis. Penyerapan zinc diatur oleh protein ZIP1, berperan meningkatkan kandungan zinc sitoplasmik intrasel dengan membawa zinc dari cairan ekstrasel. Kadar zinc yang tinggi dan ekspresi protein ZIP1 banyak ditemukan pada epitel prostat normal, sedangkan pada kanker prostat ditemukan sedikit atau tidak ada ekspresi protein ZIP1. Penurunan ekspresi ZIP1 diduga dapat menghambat apoptosis, serta memacu perkembangan adenokarsinoma prostat. Penelitian ini bertujuan menganalisis korelasi ekspresi protein ZIP1 dan Caspase- 3 pada jaringan adenokarsinoma prostat berdasarkan Gleason score yang berbeda. Metode: Desain studi analitik retrospektif dengan desain potong lintang. Sampel penelitian ini adalah 31 sediaan blok parafin adenokarsinoma prostat yang memenuhi kriteria inklusi. Sediaan dipulas menggunakan teknik imunohistokimia untuk mengetahui ekspresi protein ZIP1 dan caspase-3. Ekspresi protein pada pulasan slide dihitung menggunakan program imageJ. Gleason score sebagai data sekunder yang didapatkan dari laporan kasus. Korelasi ekspresi kedua protein berdasarkan Gleason score dianalisis dengan uji korelasi Pearson menggunakan SPSS 11.5. Hasil: Rerata positivitas ekspresi ZIP1 pada adenokarsinoma prostate adalah 35% dan rerata positivitas caspase-3 adalah 33%. Terdapat korelasi positif bermakna antara ekspresi ZIP1 dan caspase-3 (r = 0.379 , p = 0,018). Terdapat korelasi positif antara ekspresi ZIP1 dan caspase-3 pada kelompok intermediate grade (r = 0.73, p = 0.01) dan korelasi lemah tidak bermakna pada kelompok high grade (r = 0.04, p = 0.48). Kesimpulan: Terdapat korelasi positif antara ekspresi ZIP1 dan ekspresi caspase- 3 pada adenokarsinoma prostat.

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Introduction: Carcinogenesis of adenocarcinoma of the prostate occurs due to dysregulation of zinc level within the cells. Intracellular zinc molecules contributes to mitochondrial aerobic metabolism. Its influx is regulated by a transporter protein ZIP1, whose non-presence is predicted to inhibit apoptosis, thus leads to the development of prostate adenocarcinoma. This study was aimed to analyze the correlation of ZIP1 and Caspase-3 expression in prostate adenocarcinoma with respect to its grading as represented by Gleason Score.

Methods: This was a cross-sectional, retrospective analytical study on 31 formalyn-fixed, paraffin-embedded tissue that meet inclusion criteria. The specimen was stained using immunohistochemical technique for ZIP1 and Caspase-3. Protein expression of each case were counted using ImageJ analysis. Gleason score were acquired as secondary data from the cases’ reports. The correlation of their expression with respect of Gleason score were analyzed with Pearson’s correlation using SPSS 11.5.

Results: Mean expression level of ZIP1 and Caspase-3 in prostate adenocarcinoma were 35% and 33%, respectively. There was a significantly positive correlation between ZIP1 and Caspase-3 expression (r=0.379; p=0.018). However, their correlation was stronger in intermediate-grade group (r=0.73; p=0.01) and the correlation was much weaker in high-grade group (r=0.04; p=0.48).

Conclusion: There was a positive correlation between ZIP1 and caspase-3 expression in adenocarcinoma prostate."

"Pendahuluan: Penurunan kadar Zink (Zn) pada prostat berkorelasi dengan peningkatan skor Gleason adenokarsinoma prostat dan menyebabkan rendahnya Caspase-3 sebagai eksekutor apoptosis. Tingkat ekspresi transporter Zn pada sel tumor prostat berhubungan dengan tingkat keganasannya. ZnT-1 merupakan transporter Zn ke luar sel prostat, sedangkan ZIP-1 merupakan transporter Zn ke dalam sel prostat. Ekspresi ZIP-1 turun pada adenokarsinoma prostat. Korelasi ZnT-1, ZIP-1 dan Caspase-3 diduga berpengaruh dalam karsinogenesis prostat, sehingga berpotensi untuk menjadi faktor prognosis adenokarsinoma prostat. Tujuan: Mempelajari korelasi ekspresi ZnT-1 dan aktivasi Caspase-3 terhadap skor Gleason, menganalisis korelasi ekspresi ZIP-1, ZnT-1 dan aktivasi Caspase- 3, serta mengetahui profil ekspresi ZnT-1 pada jaringan adenokarsinoma prostat yang berbeda skor Gleason, dibandingkan dengan jaringan Benign Prostatic Hyperplasia (BPH). Desain: Studi retrospektif analitik potong lintang. Metode: Sampel penelitian ini adalah 31 blok parafin prostat yang dikelompokkan menjadi BPH, adenokarsinoma prostat skor Gleason ≤ 7 dan skor Gleason > 7. Ekspresi ZnT-1 dinilai dengan pulasan imunohistokimia. Data ekspresi ZIP-1 dan Caspase-3 merupakan data sekunder dari penelitian Septiawan et al. Hasil: Ekspresi ZnT-1 berkorelasi dengan skor Gleason adenokarsinoma prostat. Ekspresi ZIP-1 berkorelasi dengan aktivasi Caspase-3 pada adenokarsinoma prostat dan adenokarsinoma prostat skor Gleason ≤ 7. Ekspresi ZnT-1 berkorelasi dengan ekspresi ZIP-1 pada adenokarsinoma prostat skor Gleason > 7. Ekspresi ZIP-1 berkorelasi kuat dengan aktivasi Caspase-3 pada adenokarsinoma prostat skor Gleason 8. Ekspresi ZnT-1 pada adenokarsinoma prostat skor Gleason > 7 lebih rendah dibandingkan pada skor Gleason ≤ 7, tetapi tidak dapat dianalisis kemaknaan perbedaannya dengan BPH karena hanya diperoleh 1 sampel BPH pada penelitian ini. Kesimpulan: Transporter Zn berpotensi untuk menjadi faktor prognosis adenokarsinoma prostat.

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Background: Decreased levels of Zinc ( Zn ) in the prostate correlates with an increase in the grade Gleason score of prostate adenocarcinoma and decrease in Caspase-3 as apoptosis executor. Zn transporter expression levels in prostate tumor cells associates with the level of malignancy. The ZnT-1 is Zn exporter, while the ZIP-1 is Zn importer of prostate cells. ZIP-1 expression drops on adenocarcinoma prostate. Correlation ZnT-1, ZIP-1 and Caspase-3 allegedly influential in prostate carcinogenesis and potential to be prognostic factor of prostate adenocarcinoma.

Objective: To analyze the correlation ZnT-1 and Caspase-3 activation of the gleason score, to analyze the correlation of the expression of ZIP-1, ZnT-1 and Caspase-3 activation in adenocarcinoma prostate, and to study the profile expression of ZnT-1 in prostate adenocarcinoma with different grading of Gleason scores, compared with benign prostatic hyperplasia (BPH).

Design: A cross-sectional retrospective study analytic . Methodology: The sample is 31 paraffin blocks were grouped into BPH, prostate adenocarcinoma Gleason scored ≤ 7 and prostate adenocarcinoma Gleason scored > 7. Samples are analyzed expression of ZnT-1 by immunohistochemical staining. ZIP-1 and Caspase-3 expression is secondary data of Septiawan et al?s immunohistochemical staining.

Results: ZnT-1 expression correlated with gleason score. ZIP-1 correlated with the activation of Caspase-3 in prostate adenocarcinoma and prostate adenocarcinoma Gleason score ≤ 7. ZnT-1 correlated with ZIP-1 in prostate adenocarcinoma Gleason score > 7. ZnT-1 expression in prostate adenocarcinoma Gleason scored > 7 was lower than prostate adenocarcinoma Gleason score ≤ 7, but could not be analyzed the difference significance with BPH because there was only 1 BPH sample in this research.

Conclusion: Zn transporters have the potential to be a prognostic factor of prostate adenocarcinoma."

"ABSTRAKLatar Belakang: Beberapa studi menyebutkan bahwa penilaian kelainan yang terjadi pada prostat adalah dengan mengukur jumlah Androgen Receptor AR pada setiap kasus dan dipakai sebagai evaluasi terhadap keberhasilan terapi hormonal baik pada hiperplasia prostat/benign prostat hyperplasia BPH maupun adenokarsinoma prostat /adenocarcinoma prostate CaP . AR memerankan peran dalam proses pertumbuhan, differensiasi dan memelihara kondisi jaringan prostat tetap normal. Pada penelitian lain menyebutkan bahwa ekspresi AR positif berhubungan erat dengan gambaran derajat dan differensiasi tumor serta nilai skor Gleason. Tujuan penelitian ini untuk mengetahui perbedaan ekspresi AR pada hiperplasia prostat dan adenokarsinoma prostat.Bahan dan Metode: Penelitian ini menggunakan metode potong lintang. Sampel penelitian terdiri atas 20 kasus hiperplasia prostat dan 25 kasus adenokarsinoma prostat tipe asinar. Dilakukan pulasan imunohistokimia AR dan penilaian intensitas pulasan pada inti stromal dan inti epitel dengan menggunakan histoscore H-score . Hasil: Terdapat perbedaan bermakna kadar PSA antara hiperplasia prostat dan adenokarsinoma prostat p=0,004 . Ekspresi AR pada inti sel stromal pada hiperplasia prostat lebih tinggi dibandingkan pada adenokarsinoma prostat, dan mempunyai hasil statistik yang bermakna p=0,000 . Sedangkan ekspresi AR pada inti sel epitel menunjukkan hasil yang tidak bermakna pada kedua kelompok kasus p=0,152 . Intesitas ekspresi AR pada adenokarsinoma prostat dengan skor Gleason rendah le;7 lebih kuat dibandingkan adenokarsinoma prostat dengan skor Gleason tinggi >7 .Kesimpulan: Ekspresi AR pada inti sel stromal pada hiperplasia prostat lebih tinggi dibandingkan pada adenokarsinoma prostat. Peningkatan skor Gleason cenderung diikuti dengan penurunan intensitas ekspresi AR. Ekspresi AR pada hiperplasia prostat dan adenokarsinoma prostat dapat digunakan dalam prognosis dan prediksi serta evaluasi keberhasilan terapi hormonal.

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ABSTRACT"Background Previous studies suggested that Androgen Receptor AR expression could be used to evaluate the successful rate among patient with Benign prostate hyperplasia BPH or Adenocarcinoma acinar of the prostate CaP treated with hormonal therapy. AR plays role in prostate growth and differentiation, and maintains the normal state of the tissue. While in pathologic state, AR expression correlate with tumor grade and differentiation, and Gleason score GS . This study aimed to compare the expression of AR between BPH with CaP.Method This research use a cross sectional study conducted twenty cases of BPH and twenty five cases of CaP. Each tissue were stained using antibody against AR, and histologically reviewed. The captured photomicrographs were further analyze using histoscore H score .Result There was statistically signifinat levels PSA between BPH and CaP p 0,004 . The nucleus of stromal AR expression in BPH group compare to CaP group was statistically significant difference diagnose vs nucleus of stromal AR expression p 0,000 . Meanwhile, no significant difference is found between nucleus of epithelial AR expression between two group p 0,152 . The intensity expression AR in CaP with low Gleason score GS le 7 is higher than CaP with high Gleason score GS 7 Conclusion BPH expresess more nucleus of stromal AR than CaP. The higher Gleason score tends followed by declining intensity expression of AR. Thus suggest AR rsquo s role can use in prognosis, prediction and evaluation of hormonal theraphy of BPH or prostate malignancy."

"Latar belakang: Kanker prostat merupakan tumor ganas terbanyak ketiga pria di dunia. Penyebabnya dipengaruhi faktor usia, genetik, ras, hormonal, diet dan lingkungan. Kanker prostat dapat mengalami Neuroendocrine Differentiation NED , meningkat pada kanker prostat berdiferensiasi buruk terutama yang tidak merespon baik terhadap terapi hormonal. NED akan menentukan prognosis dan pemilihan alternatif terapi.Tujuan: Mengetahui perbedaan ekspresi Chromogranin A CgA pada adenokarsinoma prostat berdiferensiasi baik, sedang dan buruk serta kaitannya dengan derajat keganasan berdasarkan grading tumor yang diharapkan dapat menentukan prognosis dan pemilihan alternatif terapi.Metode: Studi potong lintang terhadap jaringan biopsi yang difiksasi formalin, diletakkan dalam parafin dari pasien dengan adenokarsinoma prostat berdiferensiasi baik, sedang dan buruk. Sampel penelitian dipulas dengan pewarnaan imunohistokimia CgA, diidentifikasi dan dianalisa hubungan ekspresi CgA berdasarkan usia, diagnosis histopatologik, grade groups, skor Gleason dan kadar PSA.Hasil: Ekspresi CgA positif dengan median 40 0,4-100 banyak terjadi pada kelompok usia 7. Ekspresi CgA positif dengan median 35,4 0,4-88,6 banyak terjadi dengan kadar PSA > 52,4 ?g/ml. Didapatkan hubungan bermakna antara ekspresi CgA dengan diagnosis histopatologik, grade groups dan skor Gleason p = 0, 006;p = 0,021;p = 0,006 . Tidak didapatkan hubungan bermakna antara ekspresi CgA dengan usia dan kadar PSA p = 0,412;p = 0.969 . Kesimpulan: Terdapat kecenderungan positivitas ekspresi CgA lebih banyak terjadi pada kasus adenokarsinoma prostat berdiferensiasi buruk dengan grade tinggi, yang dapat mempengaruhi prognosis dan pemilihan alternatif terapi.Kata kunci: Ekspresi Chromogranin A, adenokarsinoma prostat, grade groups, skor Gleason.

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Background Prostate cancer is the third most common malignant tumor in men worldwide. Predisposing factors of prostate cancer are influenced by age, genetics, race, hormonal, diet and environment. Prostate cancer may undergo Neuroendocrine Differentiation NED , and it found to be increase in poorly differentiated type of prostate cancer, especially who do not respond well to hormonal therapy. NED will determine the prognosis and selection of therapeutic alternatives.Objective To determine differences in expression of Chromogranin A CgA in prostate adenocarcinoma well, moderately and poor differentiated and its relationship to the tumour grading, and its effect on determining prognosis and selecting therapeutic alternatives.Methods A cross sectional study conducted to formalin fixed paraffin embedded biopsy tissue that are taken from a patient with prostate adenocarcinoma well, moderately and poor differentiated. The sample are immunohistochemical stained with CgA, identified and analyzed. The reviewed and analized it rsquo s relationship to the parameter on age, histopathological diagnosis, grade groups, Gleason score and PSA level.Results Chromogranin A positive expression with median 40 0.4 100 was found in the age 7 of prostate adenocarcinoma. CgA positive expression with median 35.4 0.4 88, 6 was found with PSA level 52.4 g ml. There were a significant difference between CgA expression with histopathological diagnosis, grade groups and Gleason score p 0, 006 p 0.021 p 0.006 . There were no significant difference between CgA expression with age and PSA level p 0.412 p 0969 .Conclusion There is a statistically significant difference of CgA expression with histopathologycal diagnosis and grade groups of prostate adenocarcinoma that reflect a worse prognosis in CgA positive group among prostate adenocarcinoma, which will need alternative therapies beside widely used hormonal therapy.Keywords Expression Chromogranin A, prostate adenocarcinoma, grade groups, Gleason score."

"ABSTRAKLatar belakang: Hiperplasia prostat dan adenokarsinoma prostat keduanyasangat dipengaruhi oleh hormon androgen terutama dihidrotestosteron(DHT) berasal dari konversi testosteron (T) dikatalisator oleh enzim 5α-reduktase (5αR). Terapi hormonal merupakan salah satu modalitas terapikedua penyakit ini dengan menghambat enzim 5αR tipe1dan tipe 2. Tujuanpenelitian ini untuk mengetahui perbedaan ekspresi 5αR1 antaraadenokarsinoma prostat tipe asinar dan hiperplasia prostat, serta melihatekspresi 5αR1 berdasarkan skor Gleason.Metode: Penelitian menggunakan metode potong lintang. Sampel terdiriatas 20 kasus adenokarsinoma prostat tipe asinar dan 20 kasus hiperplasiaprostat. Dilakukan pulasan 5αR1 dan penilaian pulasan denganmenggunakan histoscore.Hasil: Mean area sel tumor sebanyak 11,63% dan sel epitel di hiperplasiaprostat 26,54%. Terdapat perbedaan kadar PSA antara adenokarsinomaprostat dengan hiperplasia prostat (p=0,00). Ekspresi 5αR1 di sitoplasmadan inti didapatkan perbedaan antara adenokarsinoma prostat denganhiperplasia prostat (p=0,00). Ekspresi 5αR1 lemah terbanyak didapatkanpada adenokarsinoma prostat.Kesimpulan: Ekspresi dan total area pulasan intensitas 5αR1 padahiperplasia prostat lebih tinggi. Peningkatan skor Gleason cenderung diikutipenurunan ekspresi 5αR1.

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ABSTRACTBackground: Acinar adenocarcinoma and BPH both are stronglyinfluenced by androgen hormone especially dihydrotestosterone (DHT)from convertion of testosterone (T) catalize by 5α-reductase (5αR) enzyme.Hormonal therapy is one of treatment modality for these condition byinhibiting 5αR type 1 and type 2 enzyme. The aim of this study is to knowdifferential expression of 5αR1 between acinar adenocarcinoma and BPHand also expression 5αR1 based on Gleason score.Method: This was cross-sectional study on 20 cases acinar adenocarcinomaand 20 cases BPH stained with 5αR1 antibody. The appraisal was done withestimating histoscore.Result: Mean area of tumor cells is 11,63% and epithelial cells in BPH26,54%. There was statistically significant levels of PSA between acinaradenocarcinoma and BPH (p=0,00). Cytoplasmic and nuclear expression of5αR1 were statistically significant different between acinar adenocarcinomaand BPH (p=0,00). Low intensity expression of 5αR1 in acinaradenocarcinoma was the most commonly found.Conclusion: Total area of expression 5αR1 in BPH are higher. hiperplasiaprostat lebih tinggi. The higher Gleason score tends followed by decliningexpression of 5αR1.;"

"ABSTRAKLatar belakang : Insiden Adenokarsinoma di RSCM meningkat pada periode 2001-2006 dibanding periode sebelumnya 1995-2000 . Banyak penderita yang resisten terhadap pengobaan hormonal. Resistensi ini diduga akibat sel tumor mengalami transformasi Neuroendokrin. Akan dilakukan penelitian untuk melihat ekspresi Androgen Receptor AR dan Chromogranin A CgA pada adenokarsinoma prostat di RSCM tahun 2011-2015.Tujuan : Membuktikan korelasi ekspresi AR dan CgA dengan derajat keganasan.Metode : Studi potong lintang analitik terhadap 70 kasus adenokarsinoma prostat di departemen PA FKUI/RSCM tahun 2011-2015. Kasus dipulas imunohistokimia AR dan Cg A serta dilakukan interpretasi hasil. AR dinilai prosentase positivitasnya pada inti epitel dan stromal. CgA dinilai prosentase positivitasnya pada sitoplasma. Uji korelasi dilakukan untuk melihat kemaknaan dan kekuatan korelasi antar variabel terikat.Hasil : Karakteristik sampel usia 47,1 >70 tahun; diferensiasi histopatologik/skor gleason 42,9 buruk/>7, grade group 28,6 grade5 dan PSA 64,3 dalam rentang 11-100ng/ml. Ekspresi CgA berkorelasi negatif lemah dengan ekspresi AR epitel r=-0,288;p=0,016 . Ekspresi CgA tidak berkorelasi dengan ekspresi AR stromal p=0,886 . Terdapat hubungan bermakna ekspresi AR epitel dengan grade group p=0,003 . Tidak terdapat hubungan bermakna ekspresi AR epitel dengan usia, diferensiasi histopatologik/skor gleason dan PSA. Ekspresi CgA berhubungan bermakna dengan diferensiasi histopatologik/skor gleason dan grade group p=0,018;p=0,038 . Tidak terdapat hubungan bermakna ekspresi CgA dengan usia dan PSA. Ekspresi AR stromal tidak berhubungan bermakna dengan usia, diferensiasi histopatologik, grade group, skor gleason, maupun PSA.Kesimpulan : Terdapat korelasi yang lemah antara AR dan CgA sehingga pulasan AR dan CgA dapat dipakai untuk pemilihan terapi.

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ABSTRACT Background Prevalence of prostate adenocarcinoma doubled in 2001 2006 compared to 1995 2000 in RSCM. Many patients resistant to hormonal treatment. This resistance is thought to be due to tumor cells undergoing neuroendocrine transformation. Study will be conducted to analyze the expression of Androgen Receptor AR and Chromogranin A CgA in prostate adenocarcinoma at RSCM in 2011 2015. Objective To prove correlation of expression of AR and CgA with degree of malignancy. Methods A cross sectional study was carried out on 70 cases of prostate adenocarcinoma in department of Anatomic Pathology FKUI RSCM from 2011 2015. AR expressed in stromal and epithelial nuclei, CgA expressed in cytoplasm. Statistical tests used to discover significance and correlation between the dependent variables. Results Most samples are more than 70 years old 47,1 , has poor histologic gleason score 42.9 , are in clinical grade 5 28.6 , and has PSA score range between 11 100 ng ml. CgA expression negatively correlates to epithelial AR expression r 0,288 p 0.016 , while no correlation are found between CgA expression and stromal AR expression p 0.886 . There is significant difference between epithelial AR expression with grade group p 0.003 , but not with age, histopathologic differentiation Gleason score and PSA. There are significant difference between CgA expression and histopathologic differentiation grade group and Gleason score p 0.018 p 0.038 , but not with age and PSA. No significant difference observed between stromal AR expression with age, histopathologic differentiation gleason score, grade group or PSA. Conclusion There rsquo s a weak correlation between AR and CgA so that AR and CgA expression can be used for the selection of therapy. "

"Prostate Specific Antigen PSA kerap digunakan untuk skrining adenokarsinoma prostat. Meningkatnya kadar PSA pada serum dapat digunakan sebagai pendeteksi awal terdapatnya penyakit tersebut. Namun, diketahui bahwa terdapat kondisi lain yang dapat turut mempengaruhi peningkatan PSA. Salah satunya adalah hiperplasia prostat. Keadaan ini dapat mengakibatkan rancunya informasi yang didapatkan dari pemeriksaan PSA.Tujuan: Tujuan yang hendak dicapai dari pelaksanaan penelitian ini adalah membandingkan kadar serum PSA pada kasus adenokarsinoma prostat dan hiperplasia prostat yang terdiagnosis di Departemen Patologi Anatomik, Rumah Sakit Cipto Mangunkusumo. Selain itu, riset ini juga diharapkan dapat menjabarkan peran PSA sebagai marker. Metode: Penelitian ini menggunakan metode potong lintang. Data yang digunakan bersumber dari formulir permohonan yang berasal dari 53 pasien penderita adenokarsinoma prostat dan 53 pasien penderita hiperplasia prostat. Hasil: Rerata kadar serum PSA adenokarsinoma prostat adalah 309,23 ng/mL, sedangkan untuk hiperplasia prostat sebesar 15,36 ng/mL. Terdapat perbedaan signifikan pada kadar PSA pada kasus adenokarsinoma prostat dan hiperplasia prostat.

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Prostate Specific Antigen PSA has been widely used as screening tool for prostatic adenocarcinoma. The increased PSA level suggests this condition. However, it was later known that the level of serum PSA could also be elevated by a number of conditions. One of which is a benign condition called prostatic hyperplasia. Often, the information provided by PSA level becomes misleading.

Aims: This study was conducted to compare the level of PSA in prostatic adenocarcinoma and hyperplasia cases in Department of Anatomical Pathology, Cipto Mangunkusumo Hospital. Furthermore, the purpose of this study was also to elaborate the importance of PSA as diagnostic marker.

Methods: This study was conducted with cross sectional method. The source of data was obtained from request forms belonged to 53 patients diagnosed with prostatic adenocarcinoma and the other 53 patients suffer from hyperplasia.

Results: In the end of the study, there was significant PSA level difference between in cases of prostatic adenocarcinoma and hyperplasia prostate."