TAMs, VEGF dan MDV pada karsinoma duktal invasif payudara serta hubungannya dengan derajat histologis, ukuran tumor, status limfonodi dan ketahanan hidup

GUNTERSAH, Toddy, dr. Harijadi, SpPA (K)

2009 | Tesis | S2 Patologi Anatomi

Angiogenesis berperan pada progresivitas karsinoma duktal payudara. Angiogenesis pada karsinoma payudara diperantarai oleh sel tumor dan Tumor Associated Macrophages (TAMs) dengan menghasilkan Vascular endothelial growth factor (VEGF). VEGF dapat memacu pertumbuhan, pematangan dan ketahanan sel endotel sehingga meningkatkan Microvascular density (MVD). Peran angiogensis pada karsinoma payudara serta hubungannya dengan derajat histologis (grade), ukuran tumor, status limfonodi dan ketahanan hidup masih kontroversi. Diteliti 30 sediaan blok parafin yang terdiri 15 karsinoma duktal grade 1 dan 15 karsinoma grade 3. Data ukuran tumor, status limfonodi dan ketahanan hidup diperoleh dari data Patologi Anatomi dan rekam medis RS Dr. Sardjito Yogyakarta. Sediaan dicat IHC dengan MoAb anti CD 68, anti VWF dan anti VEGF dengan kromogen DAB dan pulasan balik Hematoksilin Meyer. TAMs dihitung berdasarkan banyaknya makrofag yang mengekspresikan CD 68 pada 5 area hot spots. VEGF dihitung berdasarkan banyaknya sel tumor yang mengekspresikan VEGF/ 100 sel tumor pada 5 lapang pandang. MVD dihitung berdasarkan banyaknya kapiler yang sel endotelnya mengekspresikan VWF pada 6 area perbatasan tumor dengan jaringan normal. Korelasi antara TAMs, VEGF dan MVD dengan ukuran tumor serta status limfonodi dianilisis dengan uji korelasi Pearson dan Spearman. Perbedaan jumlah TAMs, VEGF, MVD pada karsinoma duktal grade 1 dan grade 3 dianalisis dengan analisa statistik Chi square test, sedangkan pengaruhnya terhadap ketahanan hidup di uji dengan uji regresi logistik dan dibuat kurva Kaplan Meier. Pada penelitian ini didapatkan TAMs berkorelasi positif dengan VEGF 0.273 :ת) ; p:0.144) namun berkorelasi negatif dengan MVD. VEGF berkorelasi negatif dengan MVD. Ekspresi TAMs dan VEGF berkorelasi negatif dengan ukuran tumor dan status limfonodi. MVD berkorelasi positif dengan ukuran tumor 0.222 :ת) ; p:0.239) dan status limfonodi ( 0.409 :ת ; p:0.025). Tidak didapatkan perbedaan bermakna jumlah TAMs, VEGF dan MVD pada Karsinoma Duktal Invasif grade 1 dan grade 3. TAMs, VEGF dan MVD serta derajat histologis dan ukuran tumor tidak berpengaruh terhadap ketahanan hidup. Status limfonodi berpengaruh terhadap ketahanan hidup (Log rank:5.28; p:0.02). Dari penelitian ini dapat disimpulkan angiogensis (MVD) berperan terhadap progresivitas Karsinoma Duktal Invasif. Semakin tinggi skor angiogenesis semakin besar ukuran tumor dan semakin banyak jumlah limfonodi yang mengandung tumor. Status limfonodi memiliki pengaruh terhadap ketahanan hidup penderita.

Angiogenesis has an important role in the progressivity of breast carcinoma. Angiogenesis is mediated by tumor cells and Tumor associated macrophages (TAMs) by producing Vascular endothelial growth factor (VEGF). VEGF increased the growth, maturity and resistancy of endothelial cells resulting increase of Micro vascular density (MVD). The role of angiogenesis on breast carcinoma and its relationship with grade, tumor size, lymph node status and survival are still controversy. 30 paraffin blocks composed of 15 grade 1 and 15 grade 3 of invasive duct carcinoma were used in this study. The data of tumor size, lymph node status and survival were obtained from Department of Anatomic Pathology. IHC staining with MoAb against CD 68, VEGF and VWF with DAB Chromogen and counter stain Hematoxyllin Meyer were used. TAMs was counted by the amount of macrophages which are expressing CD 68 on 5 hot spots area. VEGF was counted by the amount of tumor cells which are expressing VEGF/ 100 tumor cells on five microscopic fields. MVD was counted by the amount of capillary vessels which the endothelial cells are expressing VWF. The correlation between TAMs, VEGF, MVD, tumor size as well as lymph node status were analyzed with correlation test. The differences count of TAMs, VEGF and MVD in grade 1 and grade 3 invasive duct carcinoma were analyzed with chi square test. Logistic regression test and Kaplan Meier curves were used to know the effect of TAMs, VEGF, MVD and grade, tumor size, lymph node on survival. The result showed that TAMs has a positive correlation with VEGF 0.273 :ת) ; p:0.144), but it has negative correlation with MVD. VEGF has a negative correlation with MVD. TAMs and VEGF have a negative correlation with tumor size and lymphnode status. MVD has a positive correlation with tumor size ( 0.222 :ת ; p:0.239) and lymphnode status ( 0.409 :ת ; p:0.025). There are no significanth differences of TAMs, VEGF and MVD among grade 1 and grade 3 of invasive duct carcinoma. TAMs, VEGF, MVD, grade, tumor size aren’t influence the survival, but Lymph node status influence the survival (Log rank:5.28; p:0.02). The result suggested that, angiogenesis (MVD) has important role in the progressivity of invasive ductal carcinoma. The higher the angiogenesis score, the bigger the tumor size and more lymph nodes involved by tumor. Lymph node status influence survival of invasive duct carcinoma patients.

Kata Kunci : TAMs,VEGF, MVD,Karsinoma duktal invasif, Derajat histologis, Ukuran tumor, Status limfonodi, Ketahanan hidup, MVD - Invasive duct carcinoma, Grade, Tumor size, Lymph node status, Survival