Imunoexpressão da proteína tirosina fosfatase do tipo receptor N2 no curso clínico do carcinoma inflamatório da mama: associação com macrófagos e células endoteliais

Abstract

Inflammatory Breast Carcinoma (IBC) is a rare clinical presentation, affecting 1 to 5% of breast cancer patients, with rapid progression and an unfavorable prognosis. Due to its inflammatory signs, such as hyperemia, edema, and pain, the intertwined roles of the immune system and tyrosine phosphatases in its progression are questioned. Evidence suggests a significant ally in neoplastic progression in IBC: the tumormicroenvironment. Thus, it was hypothesized that the Protein Tyrosine Phosphatase Receptor N2 (PTPRN2), as well as macrophages and endothelial cells, contribute to the aggressive clinical course of the disease. However, the role of PTPRN2 in IBC has notbeen investigated, which makes this work innovative. This study aimed to analyze theexpression of PTPRN2 in the primary tumor and adjacent tissue of inflammatorycarcinoma, as well as macrophages (CD68) and endothelial cells (CD34) in the IBC and Non-IBC (Non-Inflammatory Carcinoma) groups, associating them with clinical-pathological parameters and survival curves. This is a retrospective, cross-sectionalstudy of 34 patients, including 18 with IBC and 16 with non-IBC, at Haroldo Juaçaba Hospital. PTPRN2, CD68, and CD34 expression was quantified by immunohistochemistry and immunofluorescence. PTPRN2 demonstrated strong cytoplasmic positivity in the tumor cells. In the intergroup analysis between inflammatory and non-inflammatory breast carcinoma, the mean age of patients was 57years, with most being overweight/obese, with Ki-67 greater than 20% and positive for distant metastasis. No statistical difference was observed in PTPRN2 expression, as determined by the pathologist's analysis or histoscore. By immunofluorescence, the percentage of fluorescent area for PTPRN2 was similar between the groups. However, samples with the presence of hormone receptors and HER2 exhibited higher scores. By deconvolution analysis, higher PTPRN2 expression of PTPRN2 was observed in samples with the most favorable prognosis. Evaluation of CD68 expression by immunofluorescence revealed greater macrophage infiltration in IBC samples, with a significant association in HER2-amplified samples. Furthermore, there was increase dendothelial cell infiltration in IBC samples with negative estrogen receptor and triple-negative molecular subtypes (p < 0.05). The global survival curve showed no difference. Correlation analysis showed that PTPRN2 and CD68 are negative lycorrelated, while CD68 and CD34 are positively correlated. Thus, the present study demonstrates that PTPRN2immunostaining was more highly expressed in the primary tumor than in adjacent IBC tissue. Higher expression of the luminal subtype and amplified HER2 was observed in IBC and CANI. Furthermore, it was more highly expressed in early non-inflammatory triple-negative tumors compared to CIM,indicating a role in the disease. Macrophage and endothelial cell infiltration were prominent in the IBC tumor microenvironment and are correlated with disease progression.