Open Access Research article

Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions

Victor P Andrade1, Irina Ostrovnaya2, Venkatraman E Seshan2, Mary Morrogh3, Dilip Giri4, Narciso Olvera5, Marina De Brot6, Monica Morrow3, Colin B Begg2 and Tari A King3*

Author Affiliations

1 Department of Surgery, Hospital AC Camargo Anatomia Patológica, Predio Hilda Jacob Subsolo 2, Rua Prof. Antonio Prudente 210, Liberdade, Sao Paulo, SP 01509-010, Brazil

2 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA

3 Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA

4 Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA

5 Sloan-Kettering Institute, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA

6 Breast Research Laboratory, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA

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Breast Cancer Research 2012, 14:R103 doi:10.1186/bcr3222

Published: 9 July 2012

Abstract

Introduction

Lobular carcinoma in situ (LCIS) has been accepted as a marker of risk for the development of invasive breast cancer, yet modern models of breast carcinogenesis include LCIS as a precursor of low-grade carcinomas. We provide evidence favoring a clonal origin for LCIS and synchronous estrogen receptor-positive malignant lesions of the ductal and lobular phenotype.

Methods

Patients with prior LCIS undergoing mastectomy were identified preoperatively from 2003 to 2008. Specimens were widely sampled, and frozen blocks were screened for LCIS and co-existing malignant lesions, and were subject to microdissection. Samples from 65 patients were hybridized to the Affymetrix SNP 6.0 array platform. Cases with both an LCIS sample and an associated ductal carcinoma in situ (DCIS) or invasive tumor sample were evaluated for patterns of somatic copy number changes to assess evidence of clonal relatedness.

Results

LCIS was identified in 44 of the cases, and among these a DCIS and/or invasive lesion was also identified in 21 cases. A total of 17 tumor pairs had adequate DNA/array data for analysis, including nine pairs of LCIS/invasive lobular cancer, four pairs of LCIS/DCIS, and four pairs of LCIS/invasive ductal cancer. Overall, seven pairs (41%) were judged to be clonally related; in five (29%) evidence suggested clonality but was equivocal, and five (29%) were considered independent. Clonal pairs were observed with all matched lesion types and low and high histological grades. We also show anecdotal evidence of clonality between a patient-matched triplet of LCIS, DCIS, and invasive ductal cancer.

Conclusion

Our results support the role of LCIS as a precursor in the development of both high-grade and low-grade ductal and lobular cancers.