Identification and clinical relevance of PD-L1 expression in primary mucosal malignant melanoma of the head and neck

Abstract

Mucosal melanoma of the head and neck is a rare and aggressive tumor entity with a poor prognosis. The standard treatment is radical tumor resection, with or without adjuvant radiation, where conventional chemotherapies in advanced stage or recurrent diseases have shown little benefit. Overexpression of the programmed cell death ligand 1 (PD-L1) is a common feature in human cancer. Although PD-L1 is an acknowledged prognostic biomarker for dismal prognosis in other tumors of the head and neck, expression and clinical relevance of PD-L1 in mucosal melanoma have not been addressed so far. We assessed PD-L1 expression using immunohistochemical staining in 23 tumor samples from patients with primary mucosal melanoma and correlated expression status with clinicopathological and outcome data. Tumors were derived from the nasal cavity (43.5%), nasal sinuses (43.5%), and the conjunctiva (13%). All patients had undergone surgery; 39% of all patients received adjuvant radiation and 13% were administered systemic interferon therapy. The probability of 1- and 5-year overall survival was 87 and 34.8%, respectively. The mean overall survival was 51 months and the mean recurrence-free survival was 23 months. Immunohistochemical staining showed PD-L1 expression in 13% (3/23) of mucosal melanoma. In contrast, prominent PD-L1 staining was detected in 100% of tissue sections from a control group of cutaneous melanoma (n=9). PD-L1 expression in mucosal melanoma was not correlated with age, sex, nor anatomical localization of the tumor. Interestingly, patients with PD-L1-positive mucosal melanoma had a significantly longer recurrence-free survival (P=0.026). In contrast to cutaneous melanoma and some other malignancies, a relevant PD-L1 overexpression in mucosal melanoma could not be confirmed.

Prognostic value of programmed cell death ligand 1 expression in patients with head and neck cancer: A systematic review and meta-analysis

“…Then we carefully read the full text of the remaining citations. 17 studies [5, 19–24, 29–38] investigating the correlation between PD-L1 expression and the survival of HNC patients were included. Fig 1 details the selection process.…”

“…Budczies et al [22] and Ock et al [23] found no significant correlation between PD-L1 expression and HNC survival. Thierauf et al [24] reported that HNC patients with PD-L1-positive expression even had a significantly longer survival. As controversies still remain, there is an urgent need to conduct a meta-analysis to clarify the prognostic value of PD-L1 in HNC patients and draw a firm conclusion to guide clinical practice.…”

781 Melanoma subtypes demonstrate distinct PD-L1 expression profiles

“…30 The association between PD-L1 expression and TILs is also in keeping with a prior observation that the presence of TILs is associated with improved outcomes in acral melanoma 31 and a lower risk of metastasis in mucosal melanoma, 32 and that patients with PD-L1(+) mucosal melanoma experience a significantly longer recurrence-free survival. 33 CSD melanomas showed two distinct patterns of PD-L1 display. In cases of pure desmoplastic melanoma, PD-L1 expression by tumor cells was low, and in fact was only observed on tumor cells immediately surrounding the characteristic lymphoid aggregates.…”

The potential prognostic and predictive roles of programmed cell death protein 1 expressed by tumor-infiltrating lymphocytes in solid tumors: a meta-analysis

“…Basic research (7) Animal study (10) No survival data (12) No PD-1 OS (6) [ Figure 2A]. Another 5 studies provided data on PD-1 high or low expression and OS.…”

“…Several previous studies have reported the PD-1 by TILs is more than a predictive biomarker but as a worse prognosis marker in multiple solid tumors such as gastric cancer [4] , non-small cell lung cancer (NSCLC) [5] , renal cell cancer [6] and nasopharyngeal cancer [7] . Another studies showed that PD-1 expression is associated with favorable survival in breast cancer [8] , glioblastoma [9] , metastatic melanoma [10] , ovarian cancer [11] and primary human papillomavirus-positive head and neck cancers [12] . Furthermore, one study displayed that the positive expression of PD-1 expression is not correlated with overall survival (OS) for esophageal squamous cell carcinoma (ESCC) [13] .…”