Transcriptome-Wide Microarray Analysis to Determine Molecular Mechanisms in Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Pilot Case-Control Study

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging and potentially lethal cancer of the immune system that is associated with textured-surface breast implants. To date, over 500 cases have been reported worldwide and nearly 16 deaths have occurred as a result of receiving this type of breast implant. Conversely, no cases of BIA-ALCL have been reported in patients with smooth-surface breast implants. BIA-ALCL has been shown to occur in women undergoing breast augmentation or post-mastectomy breast reconstruction at similar frequencies. The number of reported cases continue to rise with the incidence increasing 15% over the last year alone. As such, BIA-ALCL poses a significant public health risk to women undergoing breast augmentation or implant-based breast reconstruction. Genetic susceptibility is thought to play a major role in this emerging cancer. Previous genetic studies using next-generation sequencing methods have identified oncogenic mutations in the JAK/STAT3 pathway among several others. However, both studies were limited by sample size and a lack of adequate controls, making it difficult to draw larger conclusion about the role of genetics in the pathogenesis of BIA-ALCL. As such, the molecular mechanisms that lead to tumorigenesis in BIA-ALCL remain undefined which remains a critical barrier to advancing our scientific understanding of this disease. Gene discovery by DNA microarray has led to the identification of novel genes in many cancers as well as major breakthroughs in tumor molecular biology. This study aims to utilize the systematic application of DNA microarray to measure differential gene expression in banked BIA-ALCL tumor specimens and healthy control tissue. Our study is innovative because it is the first study to use DNA microarray to determine differential gene-expression in BIA-ALCL and it is also the first study to use healthy control tissue for genetic comparisons. The genomic data generated from the microarray using ingenuity pathway analysis will provide critical information regarding the molecular mechanisms of BIA-ALCL. More importantly, these differential gene expression data will serve as the foundation for which future studies can use targeted-next generation sequencing methods to identify oncogenic mutations in this disease and will guide the direction of future BIA-ALCL research. Ultimately, the results of this study could serve as the impetus for development of clinical gene arrays that improve patient safety through preoperative risk stratification that identify high-risk women undergoing breast augmentation or implant-based breast reconstruction.