Objectives It is widely accepted that HLA-G belongs to the group of checkpoint molecules, implicated in different pathways of immune suppression allowing tumors escape. Here, we investigated HLA-G expression in vulvar squamous cell carcinoma (VSCC) to explore the potential implication of these molecules as prognostic markers.

Methods Immunohistochemistry was performed to evaluate HLA-G expression using the monoclonal antibody anti-HLA-G clone 4H84 that specifically identifies the denatured heavy chain of all HLA-G isoforms. Association with clinicopathological factors and survival were analyzed in 56 VSCC treated with radical vulvectomy. Mann-Whitney (MW) U test was used to estimate differences in HLAG levels expression in subgroups. Survival estimation was calculated by the Kaplan-Meier test.

Results HLA-G was highly expressed in 11 of the 56 (19.6%) primary tumor specimens. The high HLA-G expression level was reported in high-sized tumors (PMW=0.03) and increased invasion depth (PMW=0.01). HLA-G high expression was also noted in 72,7% of advanced stages with a borderline significance (PMW=0.08). A high level of HLA-G was not associated with tumors’ resection margins (PMW=0.18). Assessment of patients’ survival by Kaplan-Meier analysis indicated an adverse correlation between HLA-Ghigh expression and overall survival rate of VSCC patients (log-rank; P=0.000037). Therefore, the 5-year cumulative survival rates of patients with HLA-Ghigh expression was 10.5%. In the same way, HLA-G high expression reduced the disease-free survival (P=0.002).

Conclusions Our study shows that VSCC expresses high HLA-G that has been associated with an unfavorable clinical outcome. These findings suggest that HLA-G might be considered as a novel postoperative prognostic indicator for VSCC