TY - JOUR
T1 - Molecular evidence in support of the neoplastic and precursor nature of microglandular adenosis
AU - Geyer, Felipe C.
AU - Lacroix-Triki, Magali
AU - Colombo, Pierre Emmanuel
AU - Patani, Neill
AU - Gauthier, Arnaud
AU - Natrajan, Rachael
AU - Lambros, Maryou B.K.
AU - Khalifeh, Ibrahim
AU - Albarracin, Constance
AU - Orru, Sandra
AU - Marchiò, Caterina
AU - Sapino, Anna
AU - Mackay, Alan
AU - Weigelt, Britta
AU - Schmitt, Fernando C.
AU - Wesseling, Jelle
AU - Sneige, Nour
AU - Reis-Filho, Jorge S.
PY - 2012/5
Y1 - 2012/5
N2 - Aims: Microglandular adenosis (MGA) is a proliferative breast lesion, which has been proposed to be a potential precursor of triple-negative breast cancers. The aims of this study were to determine whether MGAs harbour genetic alterations and if any such genetic aberrations found in MGAs are similar to those found in matched invasive carcinomas. Methods and results: Twelve cases of MGA and/or atypical MGA (AMGA), 10 of which were associated with invasive carcinoma, were evaluated. Immunohistochemical profiling revealed that all invasive carcinomas were of triple-negative phenotype and expressed S100, cytokeratins 8/18 and 'basal' markers. The morphologically distinct components of each case (MGA, AMGA and/or invasive carcinoma) were microdissected and subjected to microarray comparative genomic hybridization. Apart from three typical MGAs, all samples harboured genetic alterations. The percentage of the genome affected by copy number aberrations in MGA/AMGA ranged from 0.5 to 61.9%, indicating varying levels of genetic instability. In three cases, MGA/AMGA displayed copy number aberrations similar to those found in matched invasive components, providing strong circumstantial evidence that MGA may constitute the substrate for the invasive carcinoma development. Conclusions: Our results support the contention that MGA can be a clonal lesion and non-obligate precursor of triple-negative breast cancer.
AB - Aims: Microglandular adenosis (MGA) is a proliferative breast lesion, which has been proposed to be a potential precursor of triple-negative breast cancers. The aims of this study were to determine whether MGAs harbour genetic alterations and if any such genetic aberrations found in MGAs are similar to those found in matched invasive carcinomas. Methods and results: Twelve cases of MGA and/or atypical MGA (AMGA), 10 of which were associated with invasive carcinoma, were evaluated. Immunohistochemical profiling revealed that all invasive carcinomas were of triple-negative phenotype and expressed S100, cytokeratins 8/18 and 'basal' markers. The morphologically distinct components of each case (MGA, AMGA and/or invasive carcinoma) were microdissected and subjected to microarray comparative genomic hybridization. Apart from three typical MGAs, all samples harboured genetic alterations. The percentage of the genome affected by copy number aberrations in MGA/AMGA ranged from 0.5 to 61.9%, indicating varying levels of genetic instability. In three cases, MGA/AMGA displayed copy number aberrations similar to those found in matched invasive components, providing strong circumstantial evidence that MGA may constitute the substrate for the invasive carcinoma development. Conclusions: Our results support the contention that MGA can be a clonal lesion and non-obligate precursor of triple-negative breast cancer.
KW - Basal-like
KW - Comparative genomic hybridization
KW - Immunohistochemistry
KW - Invasive ductal carcinoma
KW - Microglandular adenosis
KW - Triple-negative
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U2 - 10.1111/j.1365-2559.2012.04207.x
DO - 10.1111/j.1365-2559.2012.04207.x
M3 - Article
C2 - 22486256
AN - SCOPUS:84860335910
SN - 0309-0167
VL - 60
SP - E115-E130
JO - Histopathology
JF - Histopathology
IS - 6 B
ER -