Elsevier

Human Pathology

Volume 28, Issue 3, March 1997, Pages 277-282
Human Pathology

Original contribution
Loss of heterozygosity on chromosome 11 q 13 in lobular lesions of the breast using tissue microdissection and polymerase chain reaction,☆☆,

https://doi.org/10.1016/S0046-8177(97)90124-6Get rights and content

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 llql3 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 llql3 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 l1ql3 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.

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      LCIS and DCIS can be so strictly interrelated that both lesions are occasionally seen intermingled within the same lobule [17-20]. In addition, Lakhani et al [21,22] and Buerger et al [23-25] found genetic similarities between grade 1 DCIS and LN/LCIS, with losses at 16q being the central genetic event, whereas different genetic profile was observed in grades 2 and 3 DCIS [26,27]. Therefore, it seems that there are more similarities than the differences between well-differentiated DCIS/LN, and that this is more than coincidental.

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      Lakhani et al [18] reported that loss of heterozygosity at chromosomal arms exhibiting imbalance at high frequency in invasive cancer was also detected in LCIS. Nayar et al [19] showed loss of heterozygosity on the 11q13 chromosome in 50% of LCIS associated with invasive lobular cancer, whereas pure LCIS in the absence of invasive lobular cancer had a much lower frequency of loss of heterozygosity. Berx et al [20] reported that 56% of invasive lobular cancers and adjacent LCIS were characterized by loss of expression of E-cadherin adhesion molecule.

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    Presented in part at the USCAP Meeting in March 1996, Washington, DC.

    ☆☆

    Supported in part by the Elaine Snyder Research Award to Dr Silverberg.

    This is a US government work. There are no restrictions on its use.

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