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Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions

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 es...

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Autores principales: Andrade, Victor P, Ostrovnaya, Irina, Seshan, Venkatraman E, Morrogh, Mary, Giri, Dilip, Olvera, Narciso, De Brot, Marina, Morrow, Monica, Begg, Colin B, King, Tari A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680923/
https://www.ncbi.nlm.nih.gov/pubmed/22776144
http://dx.doi.org/10.1186/bcr3222
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author Andrade, Victor P
Ostrovnaya, Irina
Seshan, Venkatraman E
Morrogh, Mary
Giri, Dilip
Olvera, Narciso
De Brot, Marina
Morrow, Monica
Begg, Colin B
King, Tari A
author_facet Andrade, Victor P
Ostrovnaya, Irina
Seshan, Venkatraman E
Morrogh, Mary
Giri, Dilip
Olvera, Narciso
De Brot, Marina
Morrow, Monica
Begg, Colin B
King, Tari A
author_sort Andrade, Victor P
collection PubMed
description 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.
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spelling pubmed-36809232013-06-25 Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions Andrade, Victor P Ostrovnaya, Irina Seshan, Venkatraman E Morrogh, Mary Giri, Dilip Olvera, Narciso De Brot, Marina Morrow, Monica Begg, Colin B King, Tari A Breast Cancer Res Research Article 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. BioMed Central 2012 2012-07-09 /pmc/articles/PMC3680923/ /pubmed/22776144 http://dx.doi.org/10.1186/bcr3222 Text en Copyright ©2012 Andrade et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Andrade, Victor P
Ostrovnaya, Irina
Seshan, Venkatraman E
Morrogh, Mary
Giri, Dilip
Olvera, Narciso
De Brot, Marina
Morrow, Monica
Begg, Colin B
King, Tari A
Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions
title Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions
title_full Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions
title_fullStr Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions
title_full_unstemmed Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions
title_short Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions
title_sort clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680923/
https://www.ncbi.nlm.nih.gov/pubmed/22776144
http://dx.doi.org/10.1186/bcr3222
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