Ductal Carcinoma In Situ (DCIS) Pathology 2

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Immunohistochemical features suggestive of progression:
    • Proliferation index (Ki-67):
      • DCIS grade 2 / DIN 2 have a low proliferation index
      • DCIS grade 3 / DIN 3 have a high proliferation index
  • Immunohistochemical features suggestive of progression:
    • Protein markers:
      • Hormone receptor status:
        • ER, PR, HER2
          • Nearly all low- and intermediate-grade DCIS are ER-positive
          • 50% of high-grade DCIS are ER-negative
        • HER2 is amplified in ~34% of DCIS (vs. 13% in invasive cancer) – predominantly in high-grade lesions
        • Other protein markers:
          • COX2, p16, p53, etc
        • The majority of the protein markers correlated with grade:
          • But are associated with significant heterogeneity
  • At this point in time we do not have a single robust biomarker:
    • That can predict the risk of progression of DCIS to IBC
  • Can combinations of biomarkers predict the risk of progression (clinico-pathological prediction models)?
    • Unclear clinical validity of prediction models combining biomarkers (Schmitz, R. Cancers. 2022):
      • They lack of external validation
      • They do not include the option of active surveillance
  • Molecular features suggestive of progression:
    • Gene expression analysis:
      • Intrinsic subtypes of DCIS:
        • Higher frequency of luminal B and HER2 subtypes
        • They are NOT prognostic of recurrence in DCIS
      • Gene expression differs extensively across tumors:
        • No specific gene expression profile exists that can predict progression in DCIS
        • Confounded by intrinsic subtypes?
        • The intrinsic subtypes are related to different pathways:
          • One of the pathways is tumor micro environment
    • Genetic alterations:
      • There is an increase in genetic alterations in the progression from usual ductal hyperplasia to IBC:
        • P53 mutation within the epithelial cell
      • DCIS is a genetically advanced lesion with marked intratumoral heterogeneity:
        • The higher the grade (grade 3 DCIS / DIN3) the more genetic alterations identified
  • The majority of the studies on molecular analysis in DCIS are describing synchronous alterations:
    • They are comparing tumor cells from the DCIS or IBC from the same lesion
    • Not subsequent events from the same (untreated) lesion
  • In these lesions DCIS and IBC share most genetic mutations and copy number alterations:
    • Most common mutations:
      • PIK3CA and TP53
  • No known genetic mutations can differentiate progressive from indolent DCIS:
    • Progression of DCIS varies from patient to patient
      • The lack of clear genetic alterations helping us identify progression points us towards:
        • Tumor micro environment and stroma
  • Summary:
    • DCIS is a very heterogenous disease
    • Biological question is what drives or inhibits progression of DCIS
    • The majority of studies describes observations of varying events
    • Synchronous DCIS and IBC share most genetic alterations:
      • Though not universal, but case to case based
    • No known genetic alterations / morphological features can estimate risk of progression:
      • Leading interest towards micro environment
    • Awaiting active surveillance studies
#Arrangoiz #BreastSurgeon
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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