Abstract
BackgroundMetaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis. The immune microenvironment in MBC and its significance has not been well established due to its low incurrence rate and complex components. We aimed to investigate the diversity of immune parameters including subsets of TILs and PDL1/PD1 expression in MBC, as well as its correlation with prognosis.MethodsA total of 60 patients diagnosed with MBC from January 2006 to December 2017 were included in our study. The percentage (%) and quantification (per mm2) of TILs and presence of tertiary lymphoid structures (TLS) were evaluated by hematoxylin and eosin staining (HE). The quantification of CD4+, CD8+ TILs (per mm2), and PD-1/PDL1 expression were evaluated through immunohistochemistry and analyzed in relation to clinicopathological characteristics. A ≥ 1% membranous or cytoplasmatic expression of PD1 and PDL1 was considered a positive expression.ResultsWe found squamous cell carcinoma MBC (33/60, 55%) exhibiting most TILs of all the MBC subtypes (p = 0.043). Thirty-three of 60 (50%) of the patients had coexisting invasive ductal carcinoma of no special type (IDC-NST), and the average percentage of TILs in MBC components was lower compared with NST components (p < 0.001). Thirty (50%) patients exhibited positive (≥ 1%) PDL1 expression in their tumor cells, while 36 (60%) had positive (≥ 1%) PDL1 expression in their TILs. Twenty-seven (45%) of all the patients had positive (≥ 1%) PD1 expression in their tumor cells and 33 (55%) had PD1-positive (≥ 1%) stromal TILs. More CD8+ TILs were associated with positive PDL1 expression of tumor cells as well as positive PD1 expression in stromal cells. Greater number of stromal TILS (> 300/mm2, 20%), CD4+ TILs (> 250/mm2), and CD8+ TILs (> 70/mm2) in MBC were found associated with longer disease-free survival. Positive expression of PDL1 in tumor cells (≥ 1%) and PD1 in stromal cells (≥ 1%) were also associated with longer survival.ConclusionsThe immune characteristics differ in various subtypes as well as components of MBC. Immune parameters are key predictive factors of MBC and provide the clinical significance of applying immune checkpoint therapies in patients with MBC.
Highlights
Metaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis
Previous studies have shown that MBC is less sensitive to adjuvant therapy [2, 3] and has poorer prognosis compared with invasive ductal carcinoma in the same clinical stage [4, 5], including the triple-negative breast cancer (TNBC) [6]
Given the heterogeneous components of MBC and the prognostic significance of Tumor-infiltrated lymphocytes (TILs) and its subsets as well as programmed cell death ligand 1 (PDL1)/PD1 expression in breast cancer, we investigated the expression of PD1/PDL1 and quantified TILs to determine their association with clinicopathological features and survival outcome in a cohort of MBC
Summary
Metaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis. We aimed to investigate the diversity of immune parameters including subsets of TILs and PDL1/PD1 expression in MBC, as well as its correlation with prognosis. MBC usually lacks the expression of hormone receptor and HER2 and is considered as a subtype of triple-negative breast cancer (TNBC). Previous studies have shown that MBC is less sensitive to adjuvant therapy [2, 3] and has poorer prognosis compared with invasive ductal carcinoma in the same clinical stage [4, 5], including the TNBC [6]. The TILs and PDL1/PD1 expression were both predictors of effectiveness of immune checkpoints therapy in breast cancer [15, 16] and TILs were shown to be correlating with PDL1/PD1 expression [17]
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