Molecular and genetic abnormalities in radial scar.
Hyperplasia of usual type (HUT) may be an early precursor of breast carcinoma and has been shown to contain molecular and genetic abnormalities previously seen in more advanced breast lesions, such as allelic imbalance (AI) and coexpression of estrogen receptor-alpha (ER) and the proliferation marker Ki67. We have examined hyperplastic and other areas from within radial scar (RS) for such abnormalities, to explore whether such regions of RS are similar at the molecular and genetic level to histologically similar lesions found independent of RS. Abnormal expression of ER and Ki67 in hyperplastic foci and other histologically distinct areas within RS was detected by dual-label immunofluorescence. Subtle differences in expression patterns were seen compared to similar lesions outside RS, with a lower overall level of ER overexpression in HUT within RS (P = 0.0012) and less evidence of the abnormal ER association with Ki67 (P = 0.004). AI of chromosome 16q and 8p was detected in RS, indicating that at least some areas of RS are clonal and neoplastic, but no clear relationship to ER dysregulation was found. Different genetic losses seen in microdissected areas of the same RS indicated clonal differences between these areas. The role of RS as a marker of malignancy and relative risk of breast cancer remains uncertain. Nonetheless, here we provide evidence that some molecular and genetic changes that occur to a greater degree in breast cancer and some premalignant breast lesions are present in a minority of RS.
Iqbal
Mussawar
M
Clatterbridge Cancer Research Trust, J.K. Douglas Laboratories, Clatterbridge Hospital, Bebington, United Kingdom.
Shoker
Balvinder S
BS
Foster
Christopher S
CS
Jarvis
Christine
C
Sibson
D Ross
DR
Davies
Michael P A
MP
D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002869:Chromosome Aberrations; D002885:Chromosomes, Human, Pair 16; D002898:Chromosomes, Human, Pair 8; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D019656:Loss of Heterozygosity; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011960:Receptors, Estrogen / Q000378:metabolism
D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen