Tesis

Hubungan ekspresi Survivin dan VEGF-C dengan status metastasis kelenjar getah bening pada karsinoma payudara stadium dini = Association of Survivin and VEGF-C expression with lymph node metastasis in early stage breast carcinoma.

Latar Belakang: Status kelenjar getah bening (KGB) aksila merupakan salah satu faktor prognostik independen dan penentu pilihan tatalaksana pasien karsinoma payudara. Pasien Karsinoma payudara stadium dini umumnya memiliki kesintasan yang lebih baik dibandingkan stadium lanjut, namun adanya metastasis pada kelenjar getah bening menurunkan angka kesintasan dari 74,7% menjadi 54,2%. Diseksi KGB aksila dan sentinel lymph node biopsy untuk menentukan status KGB aksila memiliki keterbatasan, berupa risiko komplikasi dan morbiditas yang tinggi, sehingga diperlukan alternatif metode pemeriksaan preoperatif. Survivin merupakan anggota kelompok inhibitor of apoptosis protein (IAP) yang terekspresi pada berbagai jenis tumor, sedangkan vascular endothelial growth factor-C (VEGF-C) adalah anggota VEGF family yang berhubungan dengan metastasis KGB dan invasi pembuluh darah limfatik pada berbagai tumor ganas. Ekspresi survivin dan VEGF-C yang tinggi berhubungan dengan sifat yang lebih agresif dan prognosis yang buruk, namun hubungan survivin dan VEGF-C dengan prognosis karsinoma payudara belum sepenuhnya jelas. Tujuan: Penelitian ini bertujuan untuk mengetahui hubungan ekspresi survivin dan VEGFC dengan kejadian metastasis KGB pada karsinoma payudara stadium dini; serta hubungan ekspresi kedua protein tersebut pada karsinoma payudara. Metode: Penelitian analitik observasional dengan desain potong lintang pada sediaan operasi mastektomi kasus karsinoma payudara stadium dini di RSCM periode Januari 2016 sampai Desember 2019. Sampel penelitian dibagi menjadi 2 kelompok, yaitu 24 kasus karsinoma payudara stadium dini dengan metastasis kelenjar getah bening dan 24 kasus karsinoma payudara stadium dini tanpa metastasis. Pengambilan sampel penelitian dilakukan secara consecutive sampling dari kasus yang memenuhi kriteria inklusi dan tidak termasuk kriteria eksklusi. Dilakukan pulasan imunohistokimia Survivin dan VEGF-C, serta dilakukan perhitungan jumlah sel yang terpulas positif. Analisis statistik Chi-square, Mann- whitney dan Spearman dilakukan di antara dua kelompok tersebut. Hasil: Terdapat perbedaan ekspresi survivin yang bermakna pada karsinoma payudara stadium dini dengan dan tanpa metastasis kelenjar getah bening (p=0,000). Terdapat perbedaan bermakna ekspresi VEGF-C pada karsinoma payudara stadium dini dengan dan tanpa metastasis kelenjar getah bening (p=0,001). Terdapat hubungan yang bermakna antara ekspresi survivin dan VEGF-C (p=0,005), serta korelasi positif antara ekspresi survivin dan VEGF-C (r=0,423; p=0,01). Kesimpulan: Terdapat perbedaan ekspresi yang bermakna antara survivin dan VEGF-C pada karsinoma payudara stadium dini dengan status metastasis kelenjar getah bening serta terdapat hubungan hubungan antara kedua ekspresi protein tersebut.
Kata kunci: karsinoma payudara, metastasis kelenjar getah bening, survivin, VEGF-C.


Background: Axillary lymph node (ALN) status is one of the independent prognostic factor and a major determinant for treatment options for breast carcinoma patients. Patients with early stage breast carcinoma generally have a better survival than advanced stage, but the presence of lymph node metastasis decreased the survival rate from 74.7% to 54.2%. ALN dissection and sentinel lymph node biopsy (SLNB) are become the standar of care for ALN staging, but both methods are associated with high risk of surgical complications and morbidity, so alternative methods of preoperative examination are needed. Survivin is a member of the inhibitor of apoptosis protein (IAP) group which is expressed in various types of malignant tumors, while vascular endothelial growth factor-C (VEGF-C) is a member of the VEGF family which is associated with lymph node metastasis and invasion of lymphatic vessels in various malignant tumors. The high expression of survivin and VEGF-C is associated with a more aggressive nature and poor prognosis, but the relationship between survivin and VEGF-C with breast carcinoma prognosis is not completely clear. Aim: This study aims to determine the relationship between survivin and VEGF-C expression with incidence of lymph node metastasis of early stage breast carcinoma, and the relationship between the expression of these two proteins in breast carcinoma. Method: An observational analytic study with a cross-sectional design on a mastectomy operation for early stage breast carcinoma at RSCM from January 2016 to December 2019. The study sample was divided into 2 groups, 24 cases of early stage breast carcinoma with lymph node metastasis and 24 cases of early stage breast carcinoma without lymph node metastasis. The research sample was taken by consecutive sampling that met the inclusion criteria and did not include the exclusion criteria. Survivin and VEGF-C immunohistochemical staining were performed and the number of cells stained positively was calculated. Chi-square, Mann-whitney, and Spearman statistical analysis was performed between the two groups. Result: There was a significant difference in the expression of survivin in early stage breast carcinoma with and without lymph node metastasis (p=0,000). There was a significant difference in the expression of VEGF-C in early stage breast carcinoma with and without lymph node metastasis (p=0,001). There was a significant relationship between survivin and VEGF-C (p=0,005), also a positive correlation between survivin and VEGF-C (r=0,423; p=0,01). Conclusion: There was a significant difference in the expression between survivin and VEGF-C in early-stage breast carcinoma with lymph node metastatic status and there was a relationship between the two protein expressions.
Key Word: breast carcinoma, lymph node metastasis, survivin, VEGF-C