PD-L1 expression in different subtypes of cervical cancer is largely lacking. We investigated the expression of PD-L1 mRNA in human papillomavirus (HPV)-negative and HPV-positive adenocarcinoma(CADC) and squamous cell carcinoma(SCC) to determine its prevalence and the association between PD-L1 expression level and HPV infection.
RNA ISH was performed with an RNAscope 2.5 (Advanced Cell Diagnostics) according to the manufacturer’s instructions. 85 cases of formalin-fixed paraffin embedded tissue sections were evaluated for mRNA expression of PD-L1 and HPV. All cases were tested HPV DNA using WTS-PCR and multi-infected cases were tested HPV DNA using LCM-PCR. HPV and PD-L1 expression were visualized with standard bright-field microscopy and reviewed by two pathologists. Positivity was defined as 1 to 3 spots in one target cell(20-40X), scored 1. If the signal was 4 to 10 spots in one cell, more than 10 spots in one cell and lower than 10% cells are with clustered spots or more than 10 spots in one cell and more than 10% cells are with clustered spots will be scored 2,3 or 4, respectively. To obtain significance in the difference between groups was performed by Chi-square test using SPSS 24.0 software.
Our results showed that the PD-L1 positivity was found in 20 out of 71(28.2%)CADC cases, while it was found in 4 out of 14(28.6%) SCC cases. PD-L1 mRNA was expressed in 11 out of 32 (34.4%) HPV mRNA positive CADC and SCC cases and that was 13 out of 53 (24.5%) HPV mRNA negative cases. In HPV DNA positive group, PD-L1 positivity was found in 15 out of 50 (30.0%) cases. In HPV DNA-negative group, PD-L1 positivity was found in 9 out of 35(25.7%) cases. Above all, PD-L1 positivity was slightly higher in SCC and HPV-positive group than that of CADC and HPV-negative group. But no significant differences were observed in these groups.
| HPV/PD-L1 | RNA Scope PD-L1 score (case/%) | Total | |||
| 0(negative） | 1-4（positive） | ||||
|
CADC |
WTS-PCR HPV+ | HPV mRNA+ | 13(65.0%) | 7(35.0%) | 20 |
| HPV mRNA- | 12(75.0%) | 4(25.0%) | 16 | ||
| Total | 25(69.4%) | 11(30.6%) | 36 | ||
|
WTS-PCR HPV+， LCM-PCR HPV- |
HPV mRNA+ | 0(0.0%) | 0(0.0%) | 0 | |
| HPV mRNA- | 9(81.8%) | 2(18.2%) | 11 | ||
| Total | 9(81.8%) | 2(18.2%) | 11 | ||
| WTS-PCR HPV- | HPV mRNA+ | 0(0.0%) | 0(0.0%) | 0 | |
| HPV mRNA- | 17(70.8%) | 7(29.2%) | 24 | ||
| Total | 17(70.8%) | 7(29.2%) | 24 | ||
| SCC | WTS-PCR HPV+ | HPV mRNA+ | 8(66.7%) | 4(33.3%) | 12 |
| HPV mRNA- | 2(100.0%) | 0(0.0%) | 2 | ||
| Total | 10(71.4%) | 4(28.6%) | 14 | ||
We didn’t observe differences of PD-L1 mRNA expression between SCC and CADC or HPV+ and HPV- cervical cancer. This may due to limited SCC cases. Further research can be done to investigate the association between HPV and PD-L1 prognostic significance of PD-L1 in cervical cancer patients.
Heeren AM, Punt S, Bleeker MC, Gaarenstroom KN, van der Velden J, Kenter GG, de Gruijl TD and Jordanova ES. Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix. Modern Pathology 2016; 29: 753-763.