INTISARI Latar Belakang: Adenokarsinoma prostat

INTISARI
Latar Belakang: Adenokarsinoma prostat dapat berkembang dari lesi prekanker
yaitu PIN high-grade. Prostate Spesific Antigen (PSA) adalah glikoprotein yang
diproduksi sel-sel epithelial asini dan duktus kelenjar prostat ,berperan sebagai
promotor dengan meningkatkan proliferasi sel epitel dan stroma dan kadarnya
meningkat pada proses keganasan. PSA dapat juga berperan sebagai inhibitor
angiogenesis ,sehingga PSA tidak hanya merupakan Androgen receptor (AR)
target gene, tetapi dapat juga sebagai penyebab kanker prostat.
Pertumbuhan dan progresifitas tumor melibatkan berbagai macam faktor,
termasuk interaksi antara sel tumor dengan stroma. Tumor-associated
macrophages (TAMs) merupakan unsur utama pada stroma ,berperan penting
pada angiogenesis dengan memacu microvessel density (MVD). Beberapa
penelitian mendapatkan adanya hubungan yang signifikan antara level infiltrasi
makrofag dengan angiogenesis pada berbagai macam tumor, tetapi pada tumor
prostat masih belum jelas. Hubungan antara TAMs ,MVD dan kadar PSA dengan
progresifitas adenokarsinoma prostat masih perlu diteliti agar terapi dan
prognosis dapat dilakukan lebih tepat.
Tujuan : untuk mengetahui hubungan antara TAMs, MVD dan kadar PSA
dengan lesi prostat PIN high grade dan adenokarsinoma.
Material dan metode: Diteliti 76 blok parafin jaringan lesi prostat tahun 20092011 dari Instalasi Patologi Anatomi RSUP Dr.Sardjito, terdiri dari 31 PIN high
grade , 19 Adenokarsinoma derajat rendah (gleason score ≤ 7), dan 26
Adenokarsinoma derajat
tinggi (gleason score 8-10). Sediaan dicat
imunohistokimia dengan antibodi anti CD 68 dan vWF . TAMs dihitung dari
jumlah banyaknya makrofag peritumoral yang mengekspresikan CD 68 pada 6
area hot spots. vWf dihitung jumlah kapiler yang endotelnya mengekspresikan
vWF pada 6 area perbatasan antara tumor dengan jaringan normal. Kadar
PSA diperiksa dari serum pasien dengan alat Immunoenzymatic assay.
Korelasi antara TAMs, vWF dan kadar PSA dianalisis dengan uji Pearson.
Perbedaan antara kadar PSA, TAMs dan MVD pada setiap derajat histologis lesi
prostat diuji dengan ANOVA
Hasil : Pada penelitian ini kadar PSA berkorelasi signifikan dengan derajat
histologis karsinoma prostat dan lesi prostat dengan PIN high grade (p = 0,000),
namun tidak berkorelasi dengan TAMs (p=0,730) dan MVD (p = 0 ,224
).Kadar PSA tertinggi didapatkan pada adenokarsinoma derajat tinggi. TAMs
tidak berkorelasi dengan derajat histologis adenokarsinoma prostat dan PIN high
grade (p= 0,608) , serta MVD ( p= 0,600). MVD tidak berkorelasi signifikan
dengan derajat histologis adenokarsinoma dan PIN High Grade (p= 0,906).
Kesimpulan : Pada penelitian ini kadar PSA berkorelasi dengan progresifitas
adenokarsinoma prostat, sedangkan TAMs dan MVD tidak berkorelasi dengan
angiogenesis dan progresivitas lesi prostat
Kata kunci: Tumor-associated Macrophages (TAMs), Microvessel density
(MVD),PIN High grade, Gleason score, Adenokarsinoma prostat.
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ABSTRACT
Background: Prostatic adenocarcinoma may develops from High grade PIN. The
Prostat Specific Antigen (PSA) is a glycoprotein produced primarily by the
epithelial cells that line the acini and ducts of the prostate gland. PSA levels
increase with the increase of histological grade of prostatic cancer. They might
promote prostate cancer and stromal proliferation which the serum levels are
elevated. Measurements of the PSA levels correlate significantly and positively
with Gleason scores. The other role of the PSA in prostate cancer was inhibit
angiogenesis , then PSA levels was not only an Androgen Receptor (AR) target
gene, but also participated in the etiology of prostate cancer. Tumor growth and
progression involves many factors, including interaction between tumor cells
and TAMs. TAMs are main important inflammatory cells of stromal tumor and
have important roles in tumor angiogenesis which MVD reflects this process.
Studies of TAMs in various human cancers showed significant correlation with
tumor angiogenesis, but lack information in prostate cancer. More detailed
mechanism regarding the significance between TAMs, MVD and PSA levels in
prostate cancers need to be explored and so treatment and prognosis can be
determined more accurately.
Objective: To investigate significance of TAMs, MVD and PSA levelsin High
grade PIN and histological grading of prostatic adenocarcinoma, correlated with
histologic grading.
Material and Methods: Design of this research was a quantitative nonexperimental, performed by cross sectional method. Seventy sixparaffinembedded tissues of High grade PIN and Prostatic adenocarcinoma, taken from
Dr. Sardjito General Hospital in 2009-2011 collected specimens were used in this
study. Samples consist of 31 PIN High grade, 19 low grade adenocarcinoma
(gleason score ≤ 7), and 26 high grade adenocarcinoma (gleason score 8-10).
Expressionof CD68, vWFwere examined using immunohistochemistry methode.
PSA level in was examined by serum pasien with Immunoenzymatic assay. The
correlation ofeach variable was analyzed with Pearson correlation test. The
differentiation of TAMs, vWF and PSA levels in each group was analyzed with
ANOVA test.
Result: There were significantly correlation between PSA levels with histological
grading of prostatic adenocarcinoma and PIN High grade (p= 0,000), but not
correlated with TAMs (p = 0,730) and MVD (p = 0,224). TAMs were not
statistically significant with histological grading of prostatic adenocarcinoma and
PIN High grade (p= 0,608) and MVD (p = 0,600) . MVD was not significant with
histological grade of adenocarcinoma and PIN High grade (p= 0,906)
Conclusion :This study suggested that PSA levels have important role in the
progression of prostatic adenocarcinoma cancer. Meanwhile TAMs and MVD
were not influences tumor angiogenesis and progression of prostatic carcinoma
Keywords: Tumor-associated Macrophages (TAMs), Microvessel density, High
grade PIN, Gleason score, Prostatic adenocarcinoma.
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