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Genomic Differences Between Pure Ductal Carcinoma In Situ of the Breast and that Associated with Invasive Disease: a Calibrated aCGH Study

Authors' Affiliations: ¹ Division of Applied Medical Oncology and ² Department of Biostatistics, Ontario Cancer Institute/Princess Margaret Hospital; Departments of ³ Laboratory Medicine and Pathobiology and ⁴ Medical Biophysics, University of Toronto; ⁵ Department of Pathology, University Health Network, Toronto, Ontario, Canada; and ⁶ Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada

Requests for reprints: Susan J. Done, 610 University Avenue, Room 10-717, Toronto, Ontario, Canada M5G2M9. Phone: 416-946-2976; Fax: 416-340-5517; E-mail: sdone{at}uhnres.utoronto.ca.

Purpose: In the quest for new targets, genomes of ductal carcinoma in situ (DCIS) and infiltrating duct carcinoma (IDC) have been compared previously; however, genomic alterations associated with cancer progression were difficult to identify. We hypothesized that significant events can be detected by comparing lesions with a broader range of behavior: from pure DCIS to IDC associated with lymph node metastasis.

Experimental Design: Array comparative genomic hybridization, calibrated by self-self hybridization tests, was used to study 6 cases of pure DCIS and 17 cases of DCIS paired with IDC where 8 tumors had spread to the local lymph nodes.

Results: Pure DCIS exhibited a marginally higher degree of genomic complexity than DCIS and IDC components of invasive tumors. The latter two showed similarity between tumors and between components of the same tumor with several regions detected preferentially compared with pure DCIS. IDC associated with lymph node metastases showed similarity of genomic profiles as a group. Gain on 17q22-24.2 was associated with higher histologic grade, large IDC size, lymphatic/vascular invasion, and lymph node metastasis (P < 0.05).

Conclusions: Our findings suggest that DCIS and IDC are associated with specific genomic events. DCIS associated with IDC is genomically similar to the invasive component and therefore may represent either a clone with high invasive potential or invasive cancer spreading through the ducts. Specifically, gain on 17q22-24.2 is a candidate region for further testing as a predictor of invasion when detected in DCIS and predictor of nodal metastasis when detected in DCIS or IDC.