Abstract 3360: Identification of the pathway of BIA-ALCL by analyzing the difference in immune response according to the texture of the breast implant
Authors: An Sanyeowool , Ha Jeong Hyun , Koh Youngil , Jin Ung Sik , Yoon Sung-Soo 
Published: June 2022

Abstract
Breast implant-associated ALCL (BIA-ALCL) is an extremely rare type of T-cell lymphoma. According to the American Society of Plastic Surgeons (ASPS), it was first reported in 1997 and 993 cases were reported worldwide by January 2021. Scar capsule is formed around the breast implant, and effusion exists surrounding the implant. BIA-ALCL arises either from the peri-implant capsule or seroma. We tried to understand the pathogenesis of BIA-ALCL by validating the difference in immune response according to implant texture with next generation sequencing (NGS) analysis and identifying the relevant genetic variables. Peri-implant capsule tissues were collected during the implant removal surgery and used for RNA-Seq. Breast implants were inserted for either breast reconstruction or aesthetic purposes. Implant types were grouped following the surface texturing; macrotextured, microtexturedm and smooth. Three macrotextured, four microtextured, and three smooth type samples were used in this study. After aligning the data to the GRCh38 genomic reference with a STAR aligner, the expression level was quantified using RSEM. Differentially expressed gene analysis was performed between groups using DESeq2 based on the obtained TPM values. Gene set enrichment analysis (GSEA) and enrichR were performed to obtain enriched pathways. In addition, the proportion of the cell type of the dataset was calculated using CIBERSORTx.DEG analysis identified a total of 185 up-regulated genes and 81 down-regulated genes between groups (Fold change &gt; 2, fold change &lt; 0.5, Q-value &lt;= 0.05). As a result of pathway enrichment analysis using enrichR for up-regulated genes, the peroxisome proliferator-activated receptors (PPARs) signaling pathway was significantly enriched in microtextured type and smooth type compared to macrotextured type. There are three subtypes of PPAR, of which PPARγ inhibits the JAK-STAT pathway and is known to increase the suppressor of cytokine signaling. In this regard, it is expected that the macrotextured implant group, in which the PPAR signaling pathway is not enriched compared to other groups, may have affected the function of T helper cells due to dysregulation of the JAK-STAT pathway. It has been demonstrated at the whole exome level that mutations in JAK1 and STAT3 are associated with the pathogenesis of BIA-ALCL. As a result of CIBERSORTx analysis, the ratio of fibroblast in the Smooth type was small and the T cell distribution was relatively high. Identifying the various factors involved in these PPARγ related pathways and the correlation between them will lead to the development of the prognosis of breast reconstruction and the diagnosis and treatment of BIA-ALCL.
Citation Format: Sanyeowool An, Jeong Hyun Ha, Youngil Koh, Ung Sik Jin, Sung-Soo Yoon. Identification of the pathway of BIA-ALCL by analyzing the difference in immune response according to the texture of the breast implant [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3360.