title: Tumor-associated macrophage expression of PD-L1 in implants of high grade serous ovarian carcinoma: A comparison of matched primary and metastatic tumors.
abstract: Data on PD-L1 expression in high grade serous ovarian carcinoma (HGSOC) is mixed. Some studies report robust tumor staining and others identify expression limited to tumor-associated macrophages (TAM). TAM PD-L1 expression is induced in HGSOC metastatic implants from patients who have undergone chemotherapy. However, it is unclear whether TAM acquisition of PD-L1 plays a role in treatment naïve tumors. We investigated PD-L1 expression in primary ovarian tumors and matched metastatic implants from predominantly treatment-naïve HGSOC.
  
  
  
  Sixty one primary HGSOC were evaluated with PD-L1 and CD68 IHC: 40 on TMA and 21 on whole section. Whole section cases were matched to a metastatic implant. TAM were delineated by CD68. Membranous PD-L1 staining was scored separately for tumor cells and TAM.
  
  
  
  Eight percent of primary HGSOC demonstrated PD-L1 expression. In contrast, 74% showed PD-L1+ TAM. In the 16 treatment naïve cases, 13 (81.3%) demonstrated fidelity in intratumoral PD-L1 expression between the primary and metastatic site. Of the 21 matched pairs, only one case (4.8%) did not exhibit PD-L1 positive TAM in the metastatic implant and 19 (90.5%) showed fidelity across both locations. Intratumoral and immune infiltrate PD-L1 expression was not different in cases who received neoadjuvant chemotherapy compared to treatment naïve cases.
  
  
  
  PD-L1+ TAM are common in both primary and metastatic HGSOC however tumoral PD-L1 staining is rare. There was high fidelity of PD-L1 expression when comparing primary tumors and metastatic implants in treatment naïve specimens. Clinical trials are needed to determine whether tumor-associated staining correlates with clinical response to PD-1/PD-L1 inhibition.
authors.affiliation: Department of Pathology, University of Virginia Health System, PO Box 800712, Charlottesville, VA, United States. Electronic address: CEG2KC@hscmail.mcc.virginia.edu.
authors.forename: Chelsea E
authors.initials: CE
authors.lastname: Gottlieb
authors.affiliation: Department of Pathology, University of Virginia Health System, PO Box 800712, Charlottesville, VA, United States. Electronic address: AMM7R@hscmail.mcc.virginia.edu.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Mills
authors.affiliation: Department of Pathology, University of Virginia Health System, PO Box 800712, Charlottesville, VA, United States. Electronic address: jvc5b@eservices.virginia.edu.
authors.forename: Janet V
authors.initials: JV
authors.lastname: Cross
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Virginia Health System, PO Box 800712, Charlottesville, VA, United States. Electronic address: kel7j@hscmail.mcc.virginia.edu.
authors.forename: Kari L
authors.initials: KL
authors.lastname: Ring
mesh_terms: D060890:B7-H1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human
keywords: BRCA; High grade serous ovarian cancer; PD-L1; Treatment naïve; Tumor-associated macrophages