Disertasi

Peran faktor kliniko-patologik dan angiogenik endoglin (CD105) serta pecam-1 (CD31) sebagai faktor prediksi metastasis kelenjar getah bening pelvik pada kanker serviks stadium IB-IIA. = The role of clinico-pathological and angiogenic factors (Endoglin and PECAM-1) as predictors of pelvic lymph node metastasis in cervical cancer stage IB-IIA.

Latar Belakang: Faktor-faktor kliniko-patologik telah digunakan untuk memprediksi kemungkinan adanya metastasis kelenjargetah bening pelvik kanker serviks stadium ID-IIA. Selain itu telah diketahui bahwa proses angiogenesis berperan penting dalam tahap dini mekanisme terjadinya metastastasis. Tujuan penelitian ini adalah untuk menilai peran faktor kliniko-patologik serta faktor angiogenik Endoglin (CDI05) dan PECAM-l (CD31) dalam memprediksi metastasis kelenjar getah bening kanker serviks stadium ID-IIA. Metode: Penelitian ini menggunakan rancangan potong lintang, melibatkan kasus kanker serviks stadium ID-IIA dari tahun 2007-2011di RS dr. Cipto Mangunkusumo, Jakarta. Data klinis diperoleh dari catatan medis rumah sakit dan data histopatologi diambil dari laboratorium patologi antomi. Pemeriksaan imunohistokimia terhadap Endoglin dan PECAM-ldilakukan pada spesimen blok parafin yang sama. Microvessel density (MVD) dihitung berdasarkan cara Weidner. Basil: Pada penelitian ini seluruhnya diikutsertakan 92 kasus. Analisis univariat faktor-faktor kliniko-patologik (stadium, diameter tumor, derajat diferensiasi, invasi limfovaskular) didapatkan secara statistik berrnakna dalam memprediksi metastasis kelenjar getah bening. Odds ratio stadium HA dibandingkan ID adalah 2,83 (95 % Cl 1,15; 7,01) dengan nilai p 0,022. Odds ratio diameter tumor 2:.38 mm dibandingkan < 38 mm adalah 7,10 (95 % Cl 2,65; 19,04), P 0,001. Odds ratio dari derajat diferensiasi sedang dan buruk dibandingkan diferensiasi baik berturut-turut 1,92 (95 % Cl 0,64; 5,78); 2,87 (95 % Cl 0,83; 10,1) nilai p = 0.248 dan 0,097. Odds ratio invasi limfovaskular postitif dibandingkan invasi limfo- vaskular negatif adalah 5,0 (95 % Cl 1,55; 16,06) P = 0,004. Hasil analisis univariat faktor angiogenik (Endoglin dan PECAM-l) juga didapatkan secara statistik berrnakna dalam mem- prediksi metastasis kelenjar getah bening. Odds ratio microvessel density Endoglin ::::.8,3 dibandingkan MVD < 8,3 adalah 4,27 (95 % Cl 1,63; 11,14) nilai p = 0,003. Odds ratio dari MVD PECAM-l ::::.24 dibandingkan < 24 adalah 3,54 (95 % Cl 1,41; 8,88). Pada analisis multivariat faktor-faktor kliniko-patologik dan angiogenik didapatkan bahwa hanya variabel stadium, diameter tumor, derajat diferensiasi, invasi limfovaskular dan faktor angiogenik endoglin yang secara statistik dominan dalam memprediksi metastasis kelenjar getah bening pelvik pada penderita kanker serviks stadium ID-HA. Simpulan: Faktor-faktor kliniko-patologik berperan penting dalam memprediksi metastasis kelenjar getah bening. Faktor angiogenik Endoglin dan PECAM-l juga mem- punyai peran penting dalam memprediksi metastasis kelenjar getah bening, meskipun statistik menunjukkan peran Endoglin dalam hal ini lebih dominan dari PECAM-l.
Kata Kunci: angiogenesis, endoglin, kanker serviks, kelenjar getah bening, kliniko- patologi, metastasis, PECAM-1.



Background: Several clinico-pathological factors are used to predict possible lymph node metastasis in cervical cancer stage ID-HA. However angiogenesis plays an important role in the early steps of metastasis. The aim of the study was to evaluate the role of clinico-pathological and angiogenic Endoglin (CD105) and PECAM-1 (CD31) in predicting pelvic lymph node metastasis in cervical cancer stage IB-HA. Methods: Cross sectional study is carried out on patients with cervical cancer stage IB- lIA in 2007-2011 at Cipto Mangunkusumo Hospital, Jakarta. Clinical data were taken from medical records whereas histo-pathological results were retrieved from the pathology anatomy laboratory. Immuno-histo-chemical procedure was done to the same paraffin block specimens and stained with anti CD I 05 and CD31. Microvessel density of CD 105 and CD31 were calculated according to Weidner procedure. Results: A total of 92 cases were enrolled in this study. Univariate analysis of clinico- pathological factors (stage, tumor diameter, grade of differentiation, lymph-avascular invasion) proved to be statistically significant in the prediction of lymph node metastasis. Odds ratio of stage HA compared to I B is 2.83 (95 % Cl 1.15; 7.01) with p value 0.022. Odds ratio of tumor diameter 2: 38 mm compared to < 38 mm is 7.l0 (95 % Cl 2.65; 19.04), P value 0.001. Odds ratio of moderate and poorly differentiattion compared to good differentiation is respectively 1.92 (95 % Cl 0.64; 5.78); 2.87 (95 % Cl 0.83; 10.1) P value 0.248 and 0.097. Odds Ratio of positive lympho-vascular invasion compared to negative invasion is 5.0 (95 % Cl 1.55; 16.06) P value 0.004. Results of univariate analysis of angiogenic factors (Endoglin and PECAM-1) also proved to be statistically significant in predicting lymph node metastasis. Odds ratio of microvessel density Endoglin 2: 8.3 compared to < 8.3 is 4.27 (95 % Cl 1.63; 11.14) P value 0.003. Odds ratio of MVD PECAM-1 2: 24 compared to < 24 is 3.54 (95 % Cl 1.41; 8.88). However multivariate analysis of the clinico-pahological and angiogenic factors proved that only stage, tumor diameter, grade of differentiation, lymphovascular invasion, and endoglin are the more dominant variables in predicting pelvic lymph node metastasis in cervical cancer stage IB-lIA. Conclusion: Clinico-pathological factors are important in predicting lymph node metastasis. Angiogenic factors, Endoglin and to a lesser degree PECAM-1 are also significant factors in predicting lymph node metastasis.
Keywords: angiogenesis, cervical cancer, clinico-pathology, Endoglin, lymph node metastasis, PECAM-1.