Molecular and genetic abnormalities in radial scar
Mussawar Iqbal1, Balvinder S Shoker, Christopher S Foster
1Clatterbridge Cancer Research Trust, J.K. Douglas Laboratories, Clatterbridge Hospital, Bebington, United Kingdom.
Human Pathology
|August 28, 2002
Summary
Radial scars (RS) show molecular changes similar to breast cancer precursors, but with lower estrogen receptor (ER) overexpression and altered ER-Ki67 association compared to similar lesions outside RS. Some RS areas are clonal, indicating neoplastic potential.
Area of Science:
- Breast pathology
- Molecular oncology
- Cancer genetics
Background:
- Usual type hyperplasia (HUT) can precede breast carcinoma.
- HUT and other breast lesions exhibit molecular abnormalities like allelic imbalance (AI) and coexpression of estrogen receptor-alpha (ER) and Ki67.
Purpose of the Study:
- To investigate molecular and genetic abnormalities within radial scars (RS).
- To compare these abnormalities to similar lesions found independently of RS.
Main Methods:
- Dual-label immunofluorescence used to detect ER and Ki67 expression in hyperplastic foci within RS.
- Analysis of allelic imbalance (AI) in specific chromosomal regions (16q, 8p) within RS.
- Microdissection to assess clonal differences within RS.
Main Results:
- Subtle differences in ER and Ki67 expression patterns were observed in HUT within RS compared to lesions outside RS.
- Lower overall ER overexpression (P = 0.0012) and reduced abnormal ER-Ki67 association (P = 0.004) were found in HUT within RS.
- AI of 16q and 8p detected in RS, suggesting some areas are clonal and neoplastic, but no clear link to ER dysregulation was found.
- Microdissected areas within the same RS showed different genetic losses, indicating intratumoral clonal heterogeneity.
Conclusions:
- Some molecular and genetic changes associated with breast cancer and premalignant lesions are present in a subset of radial scars.
- The role of RS as a malignancy marker and breast cancer risk indicator remains uncertain.
- Evidence suggests certain areas within RS possess neoplastic characteristics and molecular alterations.
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