PD-L1/PD-1 Expression in Endometrial Clear Cell Carcinoma: A Potential Surrogate Marker for Clinical Trials

Abstract

Background. Endometrial clear cell carcinoma (ECCC) represents a rare subtype of endometrial cancer. Recently, immunotherapeutic drugs targeting programmed cell death protein 1 (PD-1)/programmed death ligand-1 (PD-L1) was associated with improved survival in several types of cancer (especially in patients with mismatch-repair (MMR)-deficient status). The aim of this study is to evaluate the correlation between the PD-L1/PD-1 axis and clinical and pathological features in strictly defined ECCC diagnosed at our institution. Design. Review of ECCC (diagnosed in the period of 2000 to 2017) identified 23 cases (n = 23) in our institution. The cases were reviewed by 2 gynecological pathologists. Estrogen receptor, progesterone receptor, napsin A, p16, and p53 were also performed so that only pure CCC cases were included. PD-L1 (SP142), PD-1, and MMR antibodies were performed. PD-L1 and PD-1 were scored in both the tumor and the peritumoral lymphocyte infiltration. Clinical and pathological features were recorded to correlate with the expression of the 2 markers. Results. Among the 23 cases, 20 cases were qualified for pure CCC by histology and immunohistochemistry patterns. Regarding PD-1 expression, 6/20 (30%) patients had positive expression in peritumoral lymphocyte infiltration. While 3/20 (15%) cases had PD-L1 either tumoral or peritumoral lymphocytes expression. Loss of MMR expression was present in 1 (5%) of 20 patients. PD-1 and/or PD-L1 expression cases tended to have deeper myometrial invasion and higher stage at presentation. Conclusions. Our results are suggestive of the roles of both PD-1 and PD-L1 in ECCCs as useful therapeutic biomarkers for immunotherapy.

The Role of Immunohistochemistry Markers in Endometrial Cancer with Mismatch Repair Deficiency: A Systematic Review

“…We identified 34 articles studying the prognosis of patients with MMRd tumors in EC [ 25 , 26 , 51 , 54 , 60 , 63 , 70 , 72 , 75 , 76 , 84 , 89 , 92 , 99 , 102 , 105 , 106 , 115 , 120 , 126 , 130 , 131 , 132 , 133 , 135 , 140 , 141 , 153 , 154 , 155 , 156 , 157 , 158 , 159 ]. The studies included an average of 191.5 samples of MMRd tumors (minimum 12, maximum 892).…”

“…MMRd tumors were associated with a lower FIGO stage in three articles [ 92 , 106 , 115 ]; 58% to 90% of low-stage EC were MMRd compared with 41.8% to 78% for MMRp tumors. MMRd tumors were associated with higher FIGO stage in six articles [ 25 , 72 , 132 , 135 , 157 , 160 ]; 58% to 66.7% in higher-stage EC were MMRd compared with 17.6% to 40.6% for MMRp tumors.…”

Correlation of PD-L1 immunohistochemical expression with microsatellite instability and p53 status in endometrial carcinoma

“…This could be translated into practice simply by testing POLE gene mutation, MSI and p53 status [4] . PD-L1 plays an important role in tumour immunology and cancer treatment, and studies have investigated the value of its expression in EC [8] , [9] , [10] .…”

“…This has had an active response for patients with gynaecological malignancies. As such, immunotherapeutic strategies need to be developed and established for patients with aggressive EC, including USC [6] , [7] , [8] , [9] . Programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) are playing a progressively important role in tumour immunology and cancer treatment.…”

Understanding the role of indoleamine-2,3-dioxygenase and stromal differentiation in rare subtype endometrial cancer

“…Many studies have demonstrated the significance of programmed death-ligand 1 (PD-L1) expression in endometrial carcinomas subtypes. 7 , 8 However, the tumoral microenvironment (TME) is complex with different cell lineages, cytokine mediators, and stroma components, and is not limited to the programmed death-ligand axis.…”