Τίτλος:
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?
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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/mm2) 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. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
Συγγραφείς:
Koletsa, T.
Kotoula, V.
Koliou, G.-A.
Manousou, K.
Chrisafi, S.
Zagouri, F.
Sotiropoulou, M.
Pentheroudakis, G.
Papoudou-Bai, A.
Christodoulou, C.
Xepapadakis, G.
Zografos, G.
Petraki, K.
Pazarli, E.
Koutras, A.
Kourea, H.P.
Bafaloukos, D.
Chatzopoulos, K.
Iliadis, A.
Markopoulos, C.
Venizelos, V.
Arnogiannaki, N.
Kalogeras, K.T.
Kostopoulos, I.
Gogas, H.
Fountzilas, G.
Περιοδικό:
Cancer Immunology, Immunotherapy
Λέξεις-κλειδιά:
antineoplastic agent; CD3 antigen; CD8 antigen; epirubicin; paclitaxel; transcription factor FOXP3; CD3 antigen; CD8 antigen; forkhead transcription factor; FOXP3 protein, human; tumor marker, adjuvant therapy; adult; aged; Article; breast cancer; cancer combination chemotherapy; cancer grading; cancer prognosis; cancer recurrence; cell density; cell proliferation; controlled study; female; follow up; human; human cell; human epidermal growth factor receptor 2 positive breast cancer; human tissue; immunohistochemistry; luminal A breast cancer; luminal B breast cancer; lymphocyte subpopulation; major clinical study; priority journal; prognostic assessment; randomized controlled trial; stroma cell; tissue microarray; triple negative breast cancer; tumor associated leukocyte; adjuvant chemotherapy; adjuvant radiotherapy; breast tumor; immunology; metabolism; middle aged; pathology; prognosis; tumor associated leukocyte; young adult, Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; CD3 Complex; CD8 Antigens; Chemotherapy, Adjuvant; Female; Follow-Up Studies; Forkhead Transcription Factors; Humans; Lymphocyte Subsets; Lymphocytes, Tumor-Infiltrating; Middle Aged; Prognosis; Radiotherapy, Adjuvant; Stromal Cells; Young Adult
DOI:
10.1007/s00262-020-02557-0
