Leukocytic Infiltration of Intraductal Carcinoma of the Prostate: An Exploratory Study

Author:

Diop Mame-Kany12ORCID,Molina Oscar Eduardo3,Birlea Mirela1,LaRue Hélène3,Hovington Hélène3,Têtu Bernard34,Lacombe Louis35ORCID,Bergeron Alain35,Fradet Yves35,Trudel Dominique126ORCID

Affiliation:

1. Centre de Recherche du Centre Hospitalier de l’Université de Montréal (axe Cancer) and Institut du Cancer de Montréal, 900 Saint-Denis, Montréal, QC H2X 0A9, Canada

2. Department of Pathology and Cellular Biology, Université de Montréal, 2900 Boulevard Édouard-Montpetit, Montréal, QC H3T 1J4, Canada

3. Centre de Recherche du CHU de Québec-Université Laval (axe Oncologie), Hôpital L’Hôtel-Dieu de Québec, 9 McMahon, Québec, QC G1R 3S3, Canada

4. Department of Pathology, CHU de Québec-Université Laval, 11 Côte du Palais, Québec, QC G1R 2J6, Canada

5. Department of Surgery, Université Laval, 2325 rue de l’Université, Québec, QC G1V 0A6, Canada

6. Department of Pathology, Centre Hospitalier de l’Université de Montréal, 1051 Sanguinet, Montréal, QC H2X 0C1, Canada

Abstract

Intraductal carcinoma of the prostate (IDC-P) is an aggressive histological subtype of prostate cancer (PCa) detected in approximately 20% of radical prostatectomy (RP) specimens. As IDC-P has been associated with PCa-related death and poor responses to standard treatment, the purpose of this study was to explore the immune infiltrate of IDC-P. Hematoxylin- and eosin-stained slides from 96 patients with locally advanced PCa who underwent RP were reviewed to identify IDC-P. Immunohistochemical staining of CD3, CD8, CD45RO, FoxP3, CD68, CD163, CD209 and CD83 was performed. For each slide, the number of positive cells per mm2 in the benign tissues, tumor margins, cancer and IDC-P was calculated. Consequently, IDC-P was found in a total of 33 patients (34%). Overall, the immune infiltrate was similar in the IDC-P-positive and the IDC-P-negative patients. However, FoxP3+ regulatory T cells (p < 0.001), CD68+ and CD163+ macrophages (p < 0.001 for both) and CD209+ and CD83+ dendritic cells (p = 0.002 and p = 0.013, respectively) were less abundant in the IDC-P tissues compared to the adjacent PCa. Moreover, the patients were classified as having immunologically “cold” or “hot” IDC-P, according to the immune-cell densities averaged in the total IDC-P or in the immune hotspots. The CD68/CD163/CD209-immune hotspots predicted metastatic dissemination (p = 0.014) and PCa-related death (p = 0.009) in a Kaplan–Meier survival analysis. Further studies on larger cohorts are necessary to evaluate the clinical utility of assessing the immune infiltrate of IDC-P with regards to patient prognosis and the use of immunotherapy for lethal PCa.

Funder

Prostate Cancer Canada with funds from the Movember Foundation

Canadian Institutes of Health Research—Institute of Cancer Research (CIHR-ICR) and the Cancer Research Society

Institut du cancer de Montréal and by internal funds from the Laboratoire d’Uro-Oncologie Expérimentale

Université de Montréal and the Institut du cancer de Montréal

Fonds de recherche du Québec-Santé

FRQS

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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