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. 2023 Sep 4;20(3):164-173.
doi: 10.4274/tjod.galenos.2023.62819.

Clear cell carcinoma of the uterine cervix; an unusual HPV-independent tumor: Clinicopathological features, PD-L1 expression, and mismatch repair protein deficiency status of 16 cases

Pınar Bulutay  1 , Özgür Can Eren  1 , Özlem Özen  2 , Asuman Nihan Haberal  2 , Nilgün Kapucuoğlu  1
Affiliations

Clear cell carcinoma of the uterine cervix; an unusual HPV-independent tumor: Clinicopathological features, PD-L1 expression, and mismatch repair protein deficiency status of 16 cases

Pınar Bulutay et al. Turk J Obstet Gynecol. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest: No conflict of interest was declared by the authors.

Figures

Figure 1
Figure 1
A-D) Histological appearance of clear cell carcinomas (CCC) and accompanying varying amounts of tumor-infiltrating lymphocytes (TILs). A- The histologic appearance of classic CCC from the high-power view (H&E x200), B- High TIL infiltration (H&E, x100), C- Moderate TIL infiltration (H&E, x100), D- Mild TIL infiltration. A few TIL clusters can be seen in the right part of the figure (H&E, x100)
Figure 2
Figure 2
A-D) The microsatellite instability (MSI) status of case no 2. A- Concurrent loss of MSH-6 in tumor cells (IHC; x200), B- Concurrent loss of MSH-2 in tumor cells (IHC; x200), C- Intact MLH-1 expression (IHC; x100), D- Intact PMS-2 expression (IHC; x100)
Figure 3
Figure 3
A- Extensive PD-L1 staining (with the 22C3 clone) in tumor and immune cells of case no 2 (TPS 90%, CPS 60%) (IHC; x200); B- A lesser degree of PD-L1 staining (with the SP263 clone) in tumor and immune cells of case no 3 (TPS 5%, CPS 20%) (IHC; x200)
See this image and copyright information in PMC

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