Hubungan Imunoekspresi Programmed Death-Ligand 1 dengan Gambaran Patologi Karsinoma Endometrium

Abstract

Latar Belakang: Karsinoma endometrium mewakili 6% kasus keganasan pada wanita di dunia, dimana ini merupakan bentuk keganasan genital yang paling sering. Keganasan ini merupakan keganasan keempat terbanyak di antara wanita dan penyebab kematian keenam yang disebabkan oleh keganasan pada tahun 2017. Di Indonesia, sebagian besar penderita karsinoma endometrium berada pada usia ≥50 tahun. Karsinoma endometrium terbagi menjadi endometrioid dan non-endometrioid secara histologi, dengan stadium awal memiliki kelangsungan hidup yang baik namun pada stadium lanjut hanya 17% dalam 5 tahun. Tatalaksana karsinoma endometrium selama 1 dekade terakhir menjadi lebih kompleks dimana belum ada terapi lini kedua setelah pembedahan dan kemoterapi. Belakangan ini imunoterapi inhibitor checkpoint pada PD-L1 telah menunjukkan hasil yang menjanjikan dalam beberapa jenis keganasan. Ini membuka sebuah pendekatan baru untuk tatalaksana karsinoma endometrium. Tujuan: Untuk menganalisis hubungan imunoekspresi PD-L1 dengan grade histologi karsinoma endometrium. Bahan dan Metode: Penelitian ini merupakan studi potong lintang untuk menganalisis imunoekspresi PD-L1 pada 23 kasus karsinoma endometrium low-grade dan 15 kasus high-grade. Sampel penelitian berupa blok parafin yang dipotong dan dilakukan pewarnaan anti – PD-L1. Evaluasi pewarnaan pada sampel dinilai dari terwarnanya membran sitoplasma sel tumor dan dinyatakan positif bila terwarnai cokelat gelap dengan minimal 5% dari area tumor serta negatif bila <5% area tumor. Ekspresi PD-L1 pada tiap grade karsinoma endometrium dikategorikan dan dianalisis dengan perangkat lunak statistik. Hasil: Ekspresi PD-L1 positif ditemukan pada 13 kasus karsinoma endometrium high-grade dan 12 kasus low-grade. Ekspresi PD-L1 ditemukan berhubungan secara signifikan dengan grade karsinoma endometrium (p = 0,028). Ekspresi PD-L1 positif cenderung terjadi pada karsinoma endometrium high-grade sebesar 3,38 kali lebih sering daripada karsinoma endometrium low-grade. Simpulan: Ekspresi PD-L1 positif ditemukan lebih banyak pada kasus karsinoma endometrium high-grade yang mencakup sebagian besar karsinoma non-endometrioid daripada kasus low-grade berupa karsinoma endometrioid low-grade dengan variannya dan mucinous carcinoma.

Background: Endometrial carcinoma represents 6% of malignant cases in women in the world, accounted as the most common genital malignancy. This malignancy is the fourth most common malignancy among women and the sixth biggest cause of death among cancers in 2017. In Indonesia, most patients with endometrial carcinoma are at the age of ≥50 years. Endometrial carcinoma is divided into endometrioid and non-endometrioid histologically, which early stage cases having good survival rate while advanced stage cases having about 17% in 5-year survival rate. Management of endometrial carcinoma over the last decade has become more complex where there is no second-line therapy after surgery and chemotherapy. Recently immune checkpoint inhibitors in PD-L1 have shown promising results in several types of malignancy. This opens up a new approach to the management of endometrial carcinoma. Aim: To analyze the association of PD-L1 immunoexpression with histologic grade of endometrial carcinoma. Material and Methods: This is a cross-sectional study to analyze PD-L1 immunoexpression in 23 cases of low-grade endometrial carcinoma and 15 cases of high-grade endometrial carcinoma. Specimens of this study were embedded in paraffin and sectioning was carried out from each block and continued with anti-PD-L1 staining. Evaluation of staining on each sample was assessed on the cytoplasmic membrane of tumor cells. It was counted as positive when ≥5% of the tumor area was stained and vice versa. The PD-L1 expression in each grade of endometrial carcinoma was categorized and analyzed by statistic software. Results: Positive PD-L1 expression was found in 13 cases of high-grade endometrial carcinoma and 12 cases of low-grade endometrial carcinoma. PD-L1 expression was found to be significantly associated with histologic grade of endometrial carcinoma (p = 0.028). Positive PD-L1 expression tends to occur in high-grade endometrial carcinoma, 3.38-fold times higher than low-grade endometrial carcinoma. Conclusion: Positive PD-L1 expression was found to be higher in high-grade endometrial carcinoma cases that included most of non-endometrioid carcinomas, than in low-grade endometrial carcinoma cases consisted of low-grade endometrioid carcinoma with its variants and mucinous carcinoma.