Date of Submission
Master of Science in Cellular and Molecular Biology
Biology and Environmental Sciences
Eva Sapi, Ph.D.
Alireza G. Senejani, Ph.D.
Nikolas Stasulli, Ph.D.
Breast Cancer Tissues, Fluorescent Immunohistochemical (IHC) Staining, TNM Staging System, Cancer Associated Infectious Agents
Borrelia burgdorferi, Breast Neoplasms, Immunohistochemistry, Chemokines, Neoplasm Staging
Borrelia burgdorferi, Breast--Cancer--Research, Immunohistochemistry--Technique, Chemokines
Borrelia burgdorferi, the causative agent of Lyme disease has been found to disseminate and colonize various organs and tissues. B. burgdorferi shows exceptional survivability by modulating its surrounding tissue environment, regulating host genes, evading the immune system, and displaying resistant forms for escaping the immune response and antibiotic treatment. Recently B. burgdorferi DNA was detected in various types of breast cancer tissues associated with poor prognosis. In vitro evidence suggests that B. burgdorferi is capable of invading and increasing the migration and invasive properties of breast cancer cells. Yet, the presence of B. burgdorferi in invasive breast cancer tissues has not been explored. This study used commercially available, FDA approved breast cancer tissue microarrays with a total of 350 ductal, 32 lobular, 22 intraductal invasive breast carcinomas, along with 29 normal breast tissues for the evaluation of the presence of B. burgdorferi by fluorescent immunohistochemical (IHC) staining technique using B. burgdorferi s.s. specific antibodies. Immunohistochemistry staining paired with high resolution (3D) tissue imaging demonstrated the presence of not only spirochetal form but also B. burgdorferi aggregates deep inside the tissues. B. burgdorferi was detected in about 20% of the invasive lobular and ductal carcinoma followed by 14% for intraductal carcinoma but none of the normal breast tissues. Further, nested PCR and direct sequencing analysis confirmed the presence of B. burgdorferi DNA. We also analyzed CXCL chemokines which are known to be involved inflammatory and tumorigenic processes and found that B. burgdorferi-positive tissues expressed both CXCL8 and CXCL10 markers 25% of the times. We further analyzed any associated trends from the available individual patient data with B. burgdorferi infection available for those commercial tissues’ array. We found cancer grades I-II and II-III correlated with the highest B. burgdorferi positive tissues. For TNM staging system, results showed that T1N0M0 and T3N1M0 have the highest percentage of B. burgdorferi positive tissues. Additionally, samples from older age groups contained the most B. burgdorferi positive breast cancer tissues. Overall, this exploratory study provided evidence to the cancer associated infectious agents’ hypothesis. Based on this study we were able to confirm the presence of B. burgdorferi in invasive breast cancer tissues and show the involvement of major CXCL family members associated inflammatory processes.
Patel, Niraj, "Evidence for the Presence of Borrelia burgdorferi in Invasive Breast Cancer Tissues" (2023). Master's Theses. 200.
Available for download on Wednesday, November 08, 2028