Prognostic relevance of the loss of stromal CD34 positive fibroblasts in invasive lobular carcinoma of the breast

Abstract

CD34+ fibroblasts are constitutive stromal components of virtually all organs, including the mammary stroma, being involved in matrix synthesis, antigen presentation, and tumor-associated stromal remodeling. The most common subtype of invasive breast carcinoma, invasive carcinoma of no special type (IBC-NST), is known for its stromal loss of CD34+ fibroblasts while acquiring alpha smooth muscle actin-positive (α-SMA+) myofibroblasts, i.e., cancer-associated fibroblasts (CAF), whereas invasive lobular carcinoma (ILC) displays partial preservation of CD34+ fibroblasts. The aim of this study was to evaluate the prognostic relevance of stromal CD34+ fibroblasts and α-SMA+ myofibroblasts in an extended collection of ILC. A total of 133 cases of ILC, primarily resected between 1996 and 2004 at University Hospital Marburg, were examined semiquantitatively for stromal content of CD34+ fibroblasts and α-SMA+ myofibroblasts. Partial preservation of CD34+ fibroblasts in the tumor stroma of ILC was confirmed. Absence of CD34+ fibroblasts in the tumor stroma significantly correlated with the presence of α-SMA+ myofibroblasts (p = 0.010), positive lymph node status (p = 0.004), and pN stage (p = 0.006). Stromal loss of CD34+ fibroblasts was significantly associated with lower overall and disease-free survival rates (p = 0.012 and 0.013, respectively). Multivariate analysis adjusted for pT and pN stage revealed stromal loss of CD34+ fibroblasts as independent prognostic parameter (p = 0.05). To our knowledge, this is the first report defining prognostically relevant stromal subtypes of ILC with long-term follow-up. Future research targeting the potential diagnostic and therapeutic implications of CD34+ fibroblasts and CAF in breast cancer, especially ILC, is a promising field of interest.

CD34+ Stromal Cells/Telocytes as a Source of Cancer-Associated Fibroblasts (CAFs) in Invasive Lobular Carcinoma of the Breast

“…Our observation of stromal cells expressing CD34 or αSMA around the strands and nests of neoplastic cells in invasive lobular carcinoma of the breast coincides with previous studies by other authors [ 34 , 42 ]. These studies included semiquantitative analysis of the differences in immunoreactivity for CD34 and αSMA in stromal cells and were mainly oriented to evaluating the prognostic relevance of the presence of one stromal cell type or another in the tumour [ 42 ]. For this purpose, the authors carried out a broad classification of the cases.…”

“…The cases of invasive lobular carcinoma were grouped according to immunoreactivity for CD34 and αSMA in stromal cells. A semiquantitative analysis was carried out by two independent observers, following the procedure used with prognostic purposes by other authors [ 42 ] and modified and simplified by us. Thus, depending on the immunoreactivity of the stromal cells, the groups were (a) predominantly positive for CD34 (>70% in the tumour area), (b) balanced for CD34 and αSMA (30–70%) and (c) predominantly positive for αSMA (>70% in the tumour area).…”

“…A recent study of invasive lobular carcinoma confirmed the partial preservation of expression in tumour stromal cells, with varying presentation of CD34+ and αSMA+ stromal cells [42]. Thus, each type of stromal cell could be absent or present (focally, predominantly or uniformly) in the tumour [42]. Both types of stromal cells can therefore coincide in the same tumour.…”

“…In addition, the characteristics, distribution and behaviour of CD34+SCs/TCs in the normal breast have been well established [3,[35][36][37][38][39][40][41]. A recent study of invasive lobular carcinoma confirmed the partial preservation of expression in tumour stromal cells, with varying presentation of CD34+ and αSMA+ stromal cells [42]. Thus, each type of stromal cell could be absent or present (focally, predominantly or uniformly) in the tumour [42].…”

A Comprehensive Investigation to Reveal the Relationship Between Plasmacytoid Dendritic Cells and Breast Cancer by Multiomics Data Analysis

“…Interleukin 6 (IL6)/STAT3 signaling enhances BRCA metastasis by interfering with estrogen receptor (ER) alpha ( Hu et al, 2020 ; Siersbaek et al, 2020 ). The expression of CD34 in BRCA tissues is positively correlated with angiogenesis, and its high expression will promote cancer cell infiltration and metastasis ( Shpall et al, 1994 ; Schulman et al, 1999 ; Westhoff et al, 2020 ).…”