Immunohistochemical and Genomic Analysis of Ductal Carcinoma in Situ of the Human Breast

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Ductal Carcinoma in Situ (DCIS) is a non obligate precursor of invasive breast cancer. Due mainly to improved screening methods the detection of DCIS has risen over the last twenty years. The inability to reliably predict progression to invasive breast cancer results in the possible overtreatment of what can be regarded as a non-life threatening condition. Current treatment options remain controversial with no consensus upon the choice of mastectomy or breast conserving surgery with or without radiotherapy or adjuvant hormone therapies. The natural progression and molecular pathology of DCIS also still remains poorly understood.

Examination of DCIS cases with known clinical outcome has been carried out using traditional pathological criteria, immunohistochemistry and genomic analysis. Tissue microarrays have been constructed and stained with a panel of antibody markers demonstrating the presence of molecular subtypes of DCIS similar to those found in invasive breast disease, although at different frequencies.

Molecular inversion probe arrays have revealed a complex heterogeneity exists in early stages of breast cancer that may be drivers of invasion. Comparison with invasive breast disease and with DCIS associated with invasive breast disease reveals a highly complex system, where progression may rely on genomic changes already established within pure DCIS or those that occur during the DCIS phase of tumourigenesis.
Date of Award2016
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorCheryl Gillett (Supervisor) & Sarah Pinder (Supervisor)

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