Abstract:
:Demonstration of identical allelic loss on chromosome 11q13 in synchronous in situ (DCIS) and invasive ductal (IDC) breast carcinoma has provided molecular evidence of the progression of DCIS to IDC. We investigated loss of heterozygosity (LOH) at chromosome 11q13 in the spectrum of "marker/premalignant" and "malignant" lobular lesions of the breast, including atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and infiltrating lobular carcinoma (ILC). Thirty-eight cases with various combinations of ALH, LCIS, and ILC were studied. Synchronous ductal lesions were present in 9 of 38 cases. Areas of interest were specifically isolated by tissue microdissection. The extracted DNA was amplified by polymerase chain reaction (PCR) and analyzed with two polymorphic markers for chromosome 11q13 (INT2 and PYGM). LOH at 11q13 was identified in ILC and LCIS in approximately one third of informative cases. LCIS in association with ILC showed a loss in 50% of cases, whereas pure LCIS in the absence of ILC had a much lower frequency of LOH, which was comparable to that of pure ALH. These results suggest that LOH on chromosome 11q13 may play an important role in development of ILC, similar to that of IDC from DCIS/ADH. Additionally, frequent LOH in ILC and LCIS associated with ILC and a significantly lower and comparable frequency of LOH in LCIS without ILC and ALH implies that genetic alteration(s) on chromosome 11q13 may be important in the transition of LCIS to ILC. LOH was detected in three of nine synchronous ductal lesions (one IDC and two DCIS), confirming our earlier findings and indicating that lobular and ductal neoplasia in the breast show some similar genetic changes. We hypothesize that LOH may help in separating morphologically similar yet genetically different subgroups of ALH and LCIS into one group with genetic changes and an increased potential to progress to invasive cancer and another group, the "marker" lesions of LCIS/ALH, that remain stable or possibly regress.
journal_name
Hum Patholjournal_title
Human pathologyauthors
Nayar R,Zhuang Z,Merino MJ,Silverberg SGdoi
10.1016/s0046-8177(97)90124-6subject
Has Abstractpub_date
1997-03-01 00:00:00pages
277-82issue
3eissn
0046-8177issn
1532-8392pii
S0046-8177(97)90124-6journal_volume
28pub_type
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