Prognostic impact of stromal and intratumoral CD3, CD8 and FOXP3 in adjuvantly treated breast cancer: do they add information over stromal tumor-infiltrating lymphocyte density?

Autor: Koletsa T; Department of Pathology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124, Thessaloníki, Greece. tkoletsa@auth.gr., Kotoula V; Department of Pathology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124, Thessaloníki, Greece.; Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki, Thessaloníki, Greece., Koliou GA; Section of Biostatistics, Hellenic Cooperative Oncology Group, Athens, Greece., Manousou K; Section of Biostatistics, Hellenic Cooperative Oncology Group, Athens, Greece., Chrisafi S; Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki, Thessaloníki, Greece., Zagouri F; Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece., Sotiropoulou M; Department of Pathology, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece., Pentheroudakis G; Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece.; Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece., Papoudou-Bai A; Department of Pathology, Ioannina University Hospital, Ioannina, Greece., Christodoulou C; Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece., Xepapadakis G; Breast Clinic, REA Hospital, Piraeus, Greece., Zografos G; Breast Unit, National and Kapodistrian University of Athens School of Medicine, Athens, Greece., Petraki K; Pathology Department, Metropolitan Hospital, Piraeus, Greece., Pazarli E; Department of Pathology, Papageorgiou Hospital, Thessaloníki, Greece., Koutras A; Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece., Kourea HP; Department of Pathology, University Hospital of Patras, Rion, Greece., Bafaloukos D; First Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece., Chatzopoulos K; Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki, Thessaloníki, Greece., Iliadis A; Department of Pathology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124, Thessaloníki, Greece., Markopoulos C; Second Department of Prop. Surgery, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece., Venizelos V; Breast Unit, Metropolitan Hospital, Piraeus, Greece., Arnogiannaki N; Department of Surgical Pathology, Saint Savvas Anticancer Hospital, Athens, Greece., Kalogeras KT; Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki, Thessaloníki, Greece.; Translational Research Section, Hellenic Cooperative Oncology Group, Athens, Greece., Kostopoulos I; Department of Pathology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124, Thessaloníki, Greece., Gogas H; First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece., Fountzilas G; Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki, Thessaloníki, Greece.; Aristotle University of Thessaloniki, Thessaloníki, Greece.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2020 Aug; Vol. 69 (8), pp. 1549-1564. Date of Electronic Publication: 2020 Apr 18.
DOI: 10.1007/s00262-020-02557-0
Abstrakt: Background: Tumor-infiltrating lymphocytes (TILs) and their subsets contribute to breast cancer prognosis. We investigated the prognostic impact of CD3+, CD8+ and FOXP3+ TILs in patients with early intermediate/high-risk breast cancer treated with adjuvant anthracycline-based chemotherapy within two randomized trials conducted by our Group.
Methods: We examined 1011 patients (median follow-up 130.9 months) and their tumors for total, stromal (s) and intratumoral (i) CD3, CD8 and FOXP3 lymphocyte density (counts/mm 2 ) on tissue-microarray cores by immunohistochemistry. Morphological sTIL density on whole H&E-stained sections was also evaluated.
Results: The majority of TILs were CD3+. Total CD3 and CD8, sCD3 and sCD8, iCD3 and iCD8, sFOXP3 and iFOXP3 were strongly correlated (Spearman's rho values > 0.6). High individual lymphocytic subsets and sTIL density were strongly associated with high tumor grade, higher proliferation and HER2-positive and triple-negative tumors (all p values < 0.001). Higher sTIL density (10% increments), high density of almost each individual marker and all-high profiles conferred favorable prognosis. However, when adjusted for sTIL density, stromal and intratumoral lymphocytic subsets lost their prognostic significance, while higher sTIL density conferred up to 15% lower risk for relapse. Independently of sTIL density, higher total CD3+ and CD8+ TILs conferred 35% and 28% lower risk for relapse, respectively.
Conclusions: Stromal and intratumoral CD3+, CD8+ and FOXP3+ TIL density do not seem to add prognostic information over the morphologically assessed sTIL density, which is worth introducing in routine histology reports.
Databáze: MEDLINE
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