Characterizing parathyroid carcinomas and atypical neoplasms based on the expression of programmed death-ligand 1 expression and the presence of tumor-infiltrating lymphocytes and macrophages.

Abstract

BACKGROUND:

Four distinct tumor microenvironments have been proposed based on the expression of programmed death-ligand 1 and the presence of tumor-infiltrating lymphocytes: immunotype I (adaptive resistance, tumor-infiltrating lymphocytes+ and programmed death-ligand 1+); immunotype II (immunologic ignorance, tumor-infiltrating lymphocytes- and programmed death-ligand 1-); immunotype III (intrinsic induction; tumor-infiltrating lymphocytes- and programmed death-ligand 1+); and immunotype IV (tolerance, tumor-infiltrating lymphocytes+ and programmed death-ligand 1-). These subtypes may predict tumor response to immunotherapy. We hypothesized that parathyroid neoplasms may have tumor immunogenic expression that can later be used to guide treatment.

METHODS:

We assessed retrospectively the immunohistochemical expression of programmed death-ligand 1 and the presence of tumor-infiltrating lymphocytes (CD3+ and CD8+) and macrophages (CD68+) in parathyroid carcinomas and in atypical parathyroid neoplasms treated at the M. D. Anderson Cancer Center from 1996 to 2016. Using intratumoral digital image analysis, the programmed death-ligand 1 H score was calculated with a standardized formula for predominant staining. The tumor-infiltrating lymphocytes per square millimeter of intratumoral areas were quantified.

RESULTS:

Within 30 specimens (17 parathyroid carcinomas and 13 atypical parathyroid neoplasms), there was no difference in the median programmed death-ligand 1 H score between the two groups (P = .57). Four parathyroid carcinoma cases had programmed death-ligand 1 H scores ≥1 associated with CD3+ and CD8+ tumor cell density; 2 of them had distant metastases. Parathyroid carcinomas had a lesser median CD3+ density (P = .04) and a lesser median CD8+ density (P =.07) than did atypical parathyroid neoplasms. Median CD68+ density did not differ between groups (P = .22).

CONCLUSION:

Parathyroid carcinomas tended to have immune-ignorant and immune-tolerant microenvironments within the neoplasm (immunotypes II and IV). Of the parathyroid carcinoma microenvironments, 17 had patterns of programmed death-ligand 1 and tumor-infiltrating lymphocytes expression (immunotype I), suggesting possible benefit from immunotherapy. In addition, both parathyroid carcinomas and parathyroid neoplasms expressed CD68+. Further exploration of these potential biomarkers as a target in cancer therapies is needed.

• Authors: Angelica Silva-Figueroa, Pamela Villalobos, Michelle D Williams, Roland L Bassett Jr, Callisia N Clarke, Jeffrey E Lee, Naifa L Busaidy, Nancy D Perrier
• Journal: Surgery (Surgery) Vol. 164 Issue 5 Pg. 960-964 (11 2018) ISSN: 1532-7361 [Electronic] United States
• PMID: 30033186 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human
• CD3 Complex
• CD68 antigen, human
• CD8 Antigens

Topics

• Adult
• Aged
• Antigens, CD (immunology, metabolism)
• Antigens, Differentiation, Myelomonocytic (immunology, metabolism)
• B7-H1 Antigen (immunology, metabolism)
• Biomarkers, Tumor (immunology, metabolism)
• CD3 Complex (immunology, metabolism)
• CD8 Antigens (immunology, metabolism)
• Female
• Humans
• Image Processing, Computer-Assisted
• Immunotherapy (methods)
• Lymphocytes, Tumor-Infiltrating (immunology, metabolism)
• Macrophages (immunology, metabolism)
• Male
• Middle Aged
• Parathyroid Glands (diagnostic imaging, immunology, pathology)
• Parathyroid Neoplasms (diagnostic imaging, immunology, pathology, therapy)
• Parathyroidectomy
• Prospective Studies
• Retrospective Studies
• Treatment Outcome
• Tumor Microenvironment (immunology)