HUBUNGAN ANTARA EKSPRESI VEGF DAN KEPADATAN MIKROVASKULAR DENGAN STADIUM, DERAJAT HISTOPATOLOGIS, DAN KETAHANAN HIDUP PADA PENDERITA KARSINOMA PAYUDARA DENGAN ER POSITIF DAN ER NEGATIF

KUKUH SUGI LAKSANA, dr. Irianiwati, Sp PA(K)

2011 | Tesis | S2 Ked.Klinik/MS-PPDS

Latar belakang: Regulasi reseptor estrogen (ER) pada vascular endothelial growth factor (VEGF) berperan penting pada angiogenesis karsinoma payudara. Peran kompleks estrogen dan ER pada angiogenesis dengan memacu VEGF dan kepadatan mikrovaskular (microvascular density/MVD). Pada karsinoma payudara, status hormonal (ER) dan angiogenesis mempengaruhi terapi dan prognosis. Angiogenesis pada karsinoma payudara ER positif dan negatif dan hubungannya dengan stadium, derajat histopatologis, dan ketahanan hidup penderita belum jelas. Tujuan: Mengetahui hubungan antara ekspresi VEGF dan MVD dengan stadium, derajat histopatologis, dan ketahanan hidup penderita karsinoma payudara dengan ER positif dan negatif. Metode: Penelitian ini bersifat retrospective cross sectional. Sampel sebanyak 50 karsinoma duktal infiltratif payudara dari RS Sardjito. Stadium ditentukan berdasarkan ukuran tumor, status limfonodi, dan metastasis. Derajat histopatologis dikelompokkan menjadi baik, sedang, dan buruk. Ketahanan hidup ditentukan sejak diagnosis ditetapkan (2003) sampai akhir penelitian (Desember 2010). Dilakukan pewarnaan imunohistokimia dengan MoAb anti ER, VEGF, dan vWF. Status ER di kelompokkan menjadi ER positif / negatif. ER positif jika >10% sel tumor mengekspresikan ER pada inti sel. Ekspresi VEGF ditentukan dari jumlah sel tumor yang sitoplasmanya tercat positif /100 sel tumor pada 5 lapang pandang. MVD ditentukan dari jumlah mikrovasa yang sel endotelnya mengekspresikan vWF pada 5 area hot spot. Hubungan antara masing-masing variabel dianalisis dengan korelasi Spearman dan Chi-Square, sedangkan hubungannya dengan ketahanan hidup dianalisis dengan tes logistik regresi dan metode Kaplan-Meier. Hasil: Pada karsinoma payudara ER positif dan ER negatif: tidak didapatkan hubungan bermakna antara ekspresi VEGF dengan ukuran tumor (p:0.789 dan p:0.254), status limfonodi (p:0.643 dan p:0.904), metastasis (p:0.124 dan p:0.327), dan derajat histopatologis (p:0.202 dan p:0.225). Tidak didapatkan hubungan antara MVD dengan ukuran tumor (p:0.849 dan p:0.967), status limfonodi (p:0.854 dan p:0.888), metastasis (p:0.095 dan p:0.897), dan derajat histopatologis (p:0.814 dan p:0.750). Tidak didapatkan hubungan antara VEGF (p:0.268 dan p:0.196) dan MVD (p:0.570 dan p:0.934) dengan ketahanan hidup penderita karsinoma payudara ER positif dan ER negatif. Ekspresi VEGF berhubungan dengan status metastasis (p:0.031), sedangkan status limfonodi berhubungan dengan ketahanan hidup penderita karsinoma payudara (p:0.027). Kesimpulan: Ekspresi VEGF dan MVD tidak berhubungan dengan beberapa parameter klinikopatologis pada karsinoma payudara dengan ER positif dan ER negatif. Ekspresi VEGF berhubungan dengan metastasis sedangkan keterlibatan limfonodi berhubungan dengan ketahanan hidup penderita karsinoma payudara.

Background: Regulation of receptor estrogen (ER) on vascular endothelial growth factor (VEGF) have a role on angiogenesis of breast carcinoma, which the role of complex estrogen and ER induce angiogenesis by influencing VEGF and microvascular density (MVD). In breast cancer, ER and angiogenesis determine its therapy and prognosis. The role of angiogenesis in ER positive and negative of breast cancer and their correlation with tumor stage, histopathological grade, and survival were not yet known. betwen the expression Aim: To investigate the correlation of VEGF and MVD with tumor stage, histopathological grade, and survival of breast cancer patient with ER positive and negative. Design Method: of the study was cross sectional with retrospective data, consists of 50 cases of invasive duct carcinoma of the breast from Sardjito Hospital. Tumor stage was established based on tumor size, lymph status, and metastasis. Histopathological grade was classified into well, moderate, and poor. Survival was determined from first diagnosis (2003) until the end of study (December 2010). The specimens were stained immunohystochemically with monoclonal antibody against ER, VEGF, and vWF. ER status was classified as ER positive and negative. Tumor with ER positive staining more than 10% was judged as ER positive. The expression of VEGF was counted based on the number of tumor cells which cytoplasm expressed VEGF/100 cancer cells in five high power fields. MVD was determined from the number of microvessels which endhotelial exspressed vWF in five hot spot areas. The correlation among its variable will be analyzed with Spearman and Chi-Square test, and the survival will be analyzed with logistic regression test and Kaplan-Maier method. Among breast cancer ER positive and negative t Result: here were: no correlation between VEGF with tumor size (p:0.789 and p:0.254), lymph node status (p:0.643 and p:0.904), metastasis (p:0.124 and p:0.327), and histopathological grade (p:0.202 and p:0.225). There were no correlation between MVD with tumor size (p:0.849 and p:0.967), lymph node status (p:0.854 and p:0.888), metastasis (p:0.095 and p:0.897), and histopathological grade (p:0.814 and p:0.750) on ER positive and negative. There were no correlation between VEGF (p:0.268 and p:0.196) and MVD (p:0.570 and p:0.934) with survival of ER positive / negative of breast cancer. VEGF expression have a correlation with tumor metastasis (p:0.031) while lymph node status have a correlation with survival breast cancer (p:0.027). The e Conclusion: xpression of VEGF and MVD have no correlation with several clinicopathologic parameter of breast cancer with ER positive and ER negative, but the expression of VEGF have a correlation with metastasis, while lymph node status have a correlation with survival.

Kata Kunci : reseptor estrogen, karsinoma payudara, VEGF, MVD, stadium, derajat histopatologis, ketahanan hidup.