Comparative genomic hybridization analysis of lobular carcinoma in situ and atypical lobular hyperplasia and potential roles for gains and losses of genetic material in breast neoplasia.
Lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) of the breast are cytologically similar breast lesions that reportedly carry different relative risks of subsequent development of invasive carcinoma. They are frequently multifocal and bilateral. We have identified the chromosomal copy number changes in 31 LCIS and 14 ALH lesions from 28 cases and also the 7 invasive carcinomas that subsequently developed in 6 of these cases. This was achieved by comparative genomic hybridization analysis of microdissected formalin-fixed, paraffin-embedded material. There was no significant difference between the aberrations found in the unilateral versus the bilateral cases of LCIS. Loss of material from 16p, 16q, 17p, and 22q and also gain of material from 6q were found at a similar high frequency in LCIS and ALH. Loss of these genomic regions may indicate the locations of genes that predispose to the development of the lesions, and the results are consistent with LCIS and ALH representing the same genetic stage of development. Comparison of the comparative genomic hybridization results from LCIS/ALH with those from ductal carcinoma in situ and invasive cancer showed some similarities at the chromosomal level, but it also showed significant differences, including gain of 1q and 8q and evidence for genomic amplification, which were not found in LCIS/ALH. A genetic model is postulated for the possible relationships between noninvasive lobular lesions and invasive breast carcinoma, delineating potential roles for specific chromosome copy number changes.
Lu
Y J
YJ
Section of Cell Biology and Experimental Pathology, Institute of Cancer Research, Surrey, United Kingdom.
Osin
P
P
Lakhani
S R
SR
Di Palma
S
S
Gusterson
B A
BA
Shipley
J M
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D002278:Carcinoma in Situ / Q000235:genetics*; D018275:Carcinoma, Lobular / Q000235:genetics*; D002869:Chromosome Aberrations; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization