Folate Receptor Alpha Immunohistochemistry in Cytology Specimens of Metastatic Breast Carcinoma

Background: Folate receptor alpha (FRA) is involved in folate accumulation and utilization, and is expressed in varying proportions in breast, ovary and parotid epithelial cells, among others. FRA overexpression by immunohistochemistry (IHC) has been shown in estrogen/progesterone receptor (ER/PR)-negative carcinoma (40-74%) and in triple-negative breast carcinoma (TNBC; 50-86%) in histological specimens of primary breast cancers. We assessed the feasibility of IHC in detecting FRA expression and its patterns and clinical significance in metastatic TNBC in fine-needle aspiration (FNA) cell blocks (CBs). Materials and Methods: Metastatic breast ductal carcinoma cases were retrospectively immunostained with FRA IHC on FNA CBs. FRA staining was scored qualitatively (+/-), by intensity (0-3) and by staining area (0-100%). Of these metastatic cases, a subset of primary breast carcinoma cases was also immunostained with FRA. The results were correlated with ER, PR and human epidermal growth factor receptor 2 (Her2/Neu) performed by routine IHC. Results: A total of 40 FNA CBs with metastatic disease were studied, including hormone (ER/PR) positive (n = 5), triple positive (n = 5), Her2/Neu-only positive (n = 5) and TNBC (n = 25). FRA IHC showed immunoreactivity with moderate positivity in only 1 (4%) TNBC. All the remaining 39 cases were negative for FRA expression. Five cases of primary TNBC were stained with FRA IHC and were negative for FRA expression. Conclusions: Our data suggest that FRA expression by IHC was rarely associated with ER/PR-negative tumors relative to ER/PR-positive tumors and, more importantly, with TNBC in FNA CBs. This finding may have a clinical significance and prognostic implications in metastatic breast carcinoma. Furthermore, 5 primary TNBC cases did not overexpress FRA by IHC. Hence, antifolate receptor therapies do not appear to be clinically relevant in TNBC based on immunostaining of FNA CBs of metastatic breast cancers.

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Utility of folate receptor alpha immunohistochemistry in cytology specimens of metastatic breast carcinoma, metastatic serous carcinoma of Müllerian origin, and primary lung adenocarcinoma

Diagnostic Cytopathology ◽

10.1002/dc.23448 ◽

2016 ◽

Vol 44 (5) ◽

pp. 369-376 ◽

Cited By ~ 1

Author(s):

Umer N. Sheikh ◽

Cynthia Cohen ◽

Momin T. Siddiqui

Keyword(s):

Breast Carcinoma ◽

Lung Adenocarcinoma ◽

Folate Receptor ◽

Metastatic Breast ◽

Serous Carcinoma ◽

Folate Receptor Alpha ◽

Metastatic Breast Carcinoma ◽

Receptor Alpha ◽

Primary Lung Adenocarcinoma

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945 Characterization of the immune landscape of malignant pleural effusion composition from patients with metastatic breast carcinoma: a pilot study

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-sitc2021.945 ◽

2021 ◽

Vol 9 (Suppl 3) ◽

pp. A993-A994

Author(s):

Caddie Dy Laberiano ◽

Edwin Parra ◽

Qiong Gan ◽

Heladio Ibarguen ◽

Shanyu Zang ◽

...

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Ductal Carcinoma ◽

Cytotoxic T Cells ◽

Metastatic Breast ◽

Absolute Number ◽

List Type ◽

Clinicopathologic Features ◽

Metastatic Breast Carcinoma ◽

Promising Tool

BackgroundBreast cancer(BC) is the second most common cause after lung cancer of malignant pleural effusions(MPEs),in approximately one third of all MPEs.Although,MPEs are relativity easy to be collated are still not well characterized in their cellular compositions. This opens new avenues to characterize the cellular milieu comprising the MPE, as it has the potential to be highly informative about mutational markers and immune response –ultimately guiding targeted therapy and predicting therapeutic outcomes with their study. The proposed study will characterize immune landscape of the cellular composition of MPE from patients with metastatic breast carcinoma and characterize their relationship with clinicopathologic features in these patients.Abstract 945 Figure 1Comparison between the cell block in H-E and mIF expression CK, CD68 and CD3Abstract 945 Figure 2Composite image in mIF expressing 8 markers. In higher magnification is possible to observe the co expression of CK+Ki67+, CK PDL1, CD3+Foxp3+ and CD3+CD8+Abstract 945 Table 1Results: cell phenotypes in percentage in the six cases analyzedAbstract 945 Table 2Clinical data of the six patients. L: left . R: right , BR : Breast cáncer, CRC: Colorrectal cáncer, NE: No evaluable , IDC : Invasive ductal carcinoma , CT: chemotherapy and BT : biotherapy* Last appointment of the patient.MethodsFive microns thickness paraffin cell pellet blocks from six cases randomly selected of breast carcinoma MPE were stained using a quantitative multiplex immunofluorescence(mIF) panel containing 8 markers against pancytokeratin(CK), PD-L1, PD-1, CD3, CD8, Foxp3, CD68, Ki67, and DAPI (figure 1). Representative regions of interest were scanned using a multispectral scanner (Vectra Polaris) in high magnification (20x) to capture different cell populations. Markers co-expression were processed and analyzed using a quantitative image analysis software (InForm). The final results were obtained as absolute number of cells from each phenotype and were characterized with clinicopathologic features.ResultsWe analyzed and stained six breast cancer MPE cases with previously optimized and validated mIF panel for formalin fixed and paraffin embedded (FFPE) tumor tissues against CK, CD3, CD68, CD8, Foxp3, Ki67, PD1 and PD-L1 (figure 2). The median cellular density was 5870.53 cells. Median for each marker: CK+ was presented in 75.9% (between malignant cells and reactive mesothelial cells) in these cells the expression of Ki67 was 8% and PD-L1+ was present in 0.2%.CD3+ was 0.72% and being the cytotoxic T-cells CD3+CD8+ was 12.13% of these cells and it expression for CD3+PD1+ was in 1.14% without concomitant expression for PD-L1. The median of the macrophages CD68+ was 8.1% of the total cells (table 2).ConclusionsmIF is a promising tool to study diverse corporal effusion from different origin. Although more studies are needed, this new perspective can help us to resolve some clues and possible prognosis in advanced stages of BC.ReferenceNicholas D T, Matthew A. S. Diagnosis and Management of Pleural Metastases and Malignant Effusion in Breast Cancer.En: Kirby I B, Edward M C, V. Suzanne K, William J. G. The Breast (Fifth Edition): Elsevier; 2018. P 934.

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