Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma

• Published in: Cancer 2004-06, Vol.100 (12), p.2562-2572
• Main Authors: Shelley Hwang, E., Nyante, Sarah J., Yi Chen, Yunn, Moore, Dan, DeVries, Sandy, Korkola, James E., Esserman, Laura J., Waldman, Frederic M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; breast neoplasms; Breast Neoplasms - genetics; Carcinoma in Situ - genetics; Carcinoma, Lobular - genetics; Chromosome Aberrations; Chromosome Deletion; comparative genomic hybridization; ductal carcinoma in situ; Female; Humans; lobular carcinoma in situ; Medical sciences; Middle Aged; Nucleic Acid Hybridization; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.20273

BACKGROUND Lobular carcinoma in situ (LCIS) of the breast is considered a marker for an increased risk of carcinoma in both breasts. However, the frequent association of LCIS with invasive lobular carcinoma (ILC) suggests a precursor‐product relation. The possible genomic relation between synchronous LCIS and ILC was analyzed using the technique of array‐based comparative genomic hybridization (CGH). METHODS Twenty‐four samples from the University of California–San Francisco pathology archives that contained synchronous LCIS and ILC were identified. Array CGH was performed using random primer–amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within synchronous LCIS and ILC were compared. RESULTS A substantial proportion of the genome was altered in samples of both LCIS and ILC. The most frequent alterations were gain of 1q and loss of 16q, both of which usually occurred as whole‐arm changes. Smaller regions of gain and loss were seen on other chromosome arms. Fourteen samples of LCIS were related more to their paired samples of ILC than to any other ILC, as demonstrated by a weighted similarity score. CONCLUSIONS LCIS and ILC are neoplastic lesions that demonstrate a range of genomic alterations. In the current study, the genetic relation between synchronous LCIS and ILC suggested clonality in a majority of the paired specimens. These data were consistent with a progression pathway from LCIS to ILC. The authors conclude that LCIS, which is known to be a marker for an environment that is permissive of neoplasia, may itself represent a precursor to invasive carcinoma. Cancer 2004. © 2004 American Cancer Society. Lobular carcinoma in situ (LCIS) of the breast is considered a marker for increased risk of carcinoma in both the ipsilateral and contralateral breast. The authors explored the genomic relation between LCIS and invasive lobular carcinoma (ILC) using the technique of array‐based comparative genomic hybridization. A clonal correlation between LCIS and ILC was found, supporting a precursor‐product correlation for LCIS and ILC. These findings support the proposition that LCIS is more than a marker for increased breast carcinoma risk.