부산대학교 도서관

Objective: Endocervical clear cell carcinoma (c-CCC) is a rare and HPV-independent adenocarcinoma type of cervix. Being usually resistant to conventional chemotherapy. Immunotherapy has recently been added as a preferred regimen as a second-line treatment option for programed cell death-ligand 1 (PD-L1)-positive or mismatch repair (MMR) deficient cervical carcinomas. In this study, clinicopathological features, PD-L1 expression, and MMR deficiency status of c-CCCs were investigated. Materials and Methods: Sixteen c-CCC diagnosed cases were included in this study. PD-L1 expression was evaluated using two different PD-L1 clones (22C3 and SP263). MMR deficiency status of the cases was evaluated using four MMR proteins (MLH1, PMS2, MSH2, and MSH6). Results: Most of the c-CCC cases were presented as FIGO Stage I (68.75%). PD-L1 expression in either tumoral or tumor-infiltrating immune cells (TILs) was present in 62.5% (10/16) and 69% (11/16) of the 22C3 and SP263 clones, respectively. Most of the cases with high TIL density were also positive for PD-L1. The PD-L1 expression rate was less than 50% in most of the cases and 12.5% of the cases shared extensive PD-L1 staining. Overall, MMR deficiency was observed in 31.25% of the cases. Most of the MMR-deficient cases (80%) were PD-L1 positive. Conclusion: Although our study cohort is limited, we have shown that PD-L1 expression and MMR deficiency can be found in c-CCCs in variable degrees. These findings suggest that accompanying TIL density and MMR deficiency could be used as candidates for predicting PD-L1 positivity for c-CCCs. However, to indicate the clinical importance of these findings, objective treatment outcomes of cases treated with immunotherapy should be seen. Keywords: Endocervical clear cell carcinoma, PD-L1 22C3, mismatch repair deficiency Amac: Endoservikal berrak hucreli karsinomlar (s-CCC), genellikle geleneksel kemoterapiye direncli olan serviksin nadir bir HPV iliskisiz adenokarsinom tipidir. Immunoterapi yakin bir zamanda programlanmis hucre olumu ligandi 1 (PD-L1)-pozitif veya mismatch-onarim (MMR) protein ekspresyon kaybi olan servikal karsinomlarin ikinci basamak tedavisinde tercih edilen bir rejim olarak eklenmistir. Bu calismada, s-CCC'lerin klinikopatolojik ozellikleri, PD-L1 ekspresyonu ve MMR eksikligi durumu arastirildi. Gerec ve Yontemler: S-CCC tanisi koyulmus olan 16 hasta bu calismaya dahil edildi. PD-L1 ekspresyonu iki farkli PD-L1 klonu (22C3 ve SP263) kullanilarak degerlendirildi. MMR eksikligi durumu dort MMR proteini ile (MLH1, PMS2, MSH2, MSH6) degerlendirildi. Bulgular: S-CCC olgularinin cogu FIGO Evre I (%68,75) olarak prezente oldu. PD-L1 ekspresyonu, tumorde ya da tumoru infiltre eden lenfositlerde (TIL) 22C3 ve SP263 klonlariyla sirayla olgularin %62,5'inde (10/16) ve %69'unda (11/16) mevcuttu. Yuksek TIL yogunluguna sahip olgularin cogu PD-L1 ile de pozitifti. PD-L1 ekspresyon orani cogu olguda %50'den azdi ve olgularin %12,5'i yaygin PD-L1 boyanmasi gosteriyordu. Genel olarak, olgularin %32,25'inde MMR proteinlerinde ekspresyon kaybi gozlendi. MMR proteinlerinde ekspresyon kaybi olan olgularin cogu (%80) PD-L1 pozitifti. Sonuc: Calisma grubumuz sinirli olmasina ragmen, PD-L1 ekspresyonu ve MMR proteinlerinde ekspresyon kaybinin s-CCClerde degisen oranlarda bulunabilecegini gosterdik. Bulgular, eslik eden TIL yogunlugunun ve MMR protein ekspresyon kaybinin, PD-L1 pozitifligini tahmin etmek icin bir aday olarak kullanilabilecegini dusundurmektedir. Ancak bu bulgularin klinik oneminin gosterilebilmesi icin immunoterapi ile tedavi edilmis olgularin objektif tedavi sonuclarinin gorulmesi gerekmektedir. Anahtar Kelimeler: Endoservikal berrak hucreli karsinom, PD-L1, 22C3, uyumsuzluk onarimi eksikligi
Introduction Clear cell carcinoma (CCC) of Mullerian origin is a rare tumor with distinct histology that may occur in the ovary, vagina, uterus and cervix. Among carcinomas of the cervix, [...]