https://openworks.mdanderson.org/sumexp22/1011/thumbnail.jp

Balema, Wintana

Fowlkes, Natalie

Krishnamurthy, Savitri

Larson, Richard

Lawrence, Alison N

Rodriguez, Megan M

Ueno, Naoto T.

Woodward, Wendy A.

English

OpenWorks @ MD Anderson

ConclusionsSince CCR7 is present in nearly all casesof IBC, including both ER+ and ER-subtypes, it should be further studied as atarget for future personalized IBCtreatments.ReferencesMego M, Gao H, Cohen EN, Anfossi S, Giordano A, Tin S, Fouad TM, De Giorgi U, Giuliano M, Woodward WA, Alvarez RH, Valero V, Ueno NT, Hortobagyi GN, Cristofanilli M, Reuben JM. Circulating tumor cells (CTCs) are associated with abnormalities in peripheral blood dendritic cells in patients with inflammatory breast cancer. Oncotarget. 2017;8(22):35656-35668. doi: 10.18632/oncotarget.10290. Van der Auwera I, Van den Eynden GG, Colpaert CG, Van Laere SJ, van Dam P, Van Marck EA, Dirix LY, Vermeulen PB. Tumor lymphangiogenesis in inflammatory breast carcinoma: a histomorphometricstudy. Clin Cancer Res. 2005;11(21):7637-42. doi: 10.1158/1078-0432.CCR-05-1142. Woodward, WA. Inflammatory breast cancer: unique biological and therapeutic considerations. The Lancet Oncology. 2015:16 (15):e568-e576. https://doi.org/10.1016/S1470-2045(15)00146-1.Next StepsCCR7 was highly expressed in 96% of tumor-containing samples, including both ER+ and ER- subtypes. Thus, it can be further studied for future personalized IBC treatments. Additionally, since all samples lacking tumors still exhibited CCR7 positivity in the stroma, the effect of stromal CCR7 on IBC development must be further explored.Further analysis includes obtaining data for the samples of unknown ER status in this study, as well as HER2 data. Future repeated studies should include patients for whom we have medical images for comparison with CCR7 pathology, as CCR7 may influence IBC clinical presentation.CCR7 Immune Cell Receptor Expression in Inflammatory Breast CancerAlison N. Lawrence1, Wintana Balema1,2,3, Savitri Krishnamurthy4, Natalie Fowlkes5, Richard Larson1,3, Megan M. Rodriguez1, Naoto T. Ueno2,3,6, Wendy A. Woodward1,2,31Department of Radiation Oncology, 2GSBS The University of Texas Health Science,3The Morgan Welch IBC Clinic and Research Program, 4Department of Pathology, 5Department of Veterinary Medicine and Surgery, 6Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Augustana CollegeIntroductionInflammatory breast cancer (IBC) is a rare form of breast cancer that is characterized by breast skin changes, such as changes in skin color, and breast swelling caused by invasion of tumor emboli into lymphatic vessels. CCR7 is an immune cell receptor known to be upregulated in IBC tumor cells that is involved in immune cell movement into lymphatics.Our objective is to understand the prevalence of CCR7 in IBC tissues and identify its association with the presence or absence of estrogen receptors (ER) in order to understand its role in IBC proliferation and potential novel therapies.Materials/MethodsA human tissue microarray (TMA) of 36 primary breast tissue biopsies from IBC patients underwent immunohistochemical staining for CCR7. The stained TMA was converted to an e-slide and  analyzed for percent of positive stain per sample using AperioImageScope software. Positivity values reflected total CCR7 presence throughout the sample, including tumor and stromal stain.In order to differentiate between positive tumor and positive stroma, the TMA was then reviewed by an expert pathologist, where tissue cores containing tumor cells (24 out of 36 samples) were evaluated for:• CCR7 positivity• Staining pattern• Percent tumor stained• IntensityResults were interpreted alongside ER status.Results – Aperio ImageScopeTable 1. CCR7 pathology results and ER status data for all tumor-containing samples. 23 samples had CCR7 tumor positivity, of which 65% had complete membranous pattern, 91% had 3+ intensity, and 61% had 100% tumor stain. Approximately half of the samples with known ER data were ER positive.Figure 4C. Tumor cells areCCR7 positive withincomplete membranouspattern, 3+ intensity, and100% stain.Figure 4A. Negative tumor.Tumor cells are present, butdo not stain positive forCCR7.Figure 4B. Tumor cells areCCR7 positive withcomplete membranouspattern, 3+ intensity, and100% stain.Figure 3B. Positive Mammary Ducts. No tumor is present, making this a false positive.Figure 3A. Positive Stroma. No tumor is present, making this a false positive.Results - PathologyPathology DataCCR7 Positivity Percent Tumor StainedPOSNEG231100%90%80%50%10%142421PatternComplete MembranousIncomplete Membranous158Intensity ER Status2+3+221ER+ER-Unknown986Figure 2. Graph of percentCCR7 positivity. All samplesexpressed CCR7 positivity inthe stroma or tumor (Median= 44%). However, thesoftware did not discriminatebetween tumor cells andstromal cells, so manysamples expressing CCR7did not actually containpositive tumor cells (SeeFigures 3A and 3B forexamples of false positives).Figure 1. Example of ImageScopeanalysis on an 84% positive sample. Red indicates a CCR7-positive area; blue is negative.

CCR7 Immune Cell Receptor Expression in Inflammatory Breast Cancer

https://openworks.mdanderson.org/cgi/viewcontent.cgi?article=1011&context=sumexp22

CCR7 Immune Cell Receptor Expression in Inflammatory Breast Cancer

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