TP53 was the sole highly recurrently mutated gene (75% in microglandular adenosis versus 88% in acinic cell carcinomas), and TP53 mutations were consistently coupled with loss of heterozygosity of the wild-type allele.
Our results demonstrate the heterogeneity of MGAs, and that MGAs associated with TNBC, but not necessarily pure MGAs, are genetically advanced, clonal, and neoplastic lesions harbouring recurrent mutations in TP53 and/or other cancer genes, supporting the notion that a subset of MGAs and AMGAs may constitute non-obligate precursors of TNBCs.
Microglandular adenosis (MGA) is a rare proliferative lesion of the breast composed of small glands lacking myoepithelial cells and lined by S100-positive, oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative epithelial cells.
Microglandular adenosis (MGA) is a rare proliferative lesion of the breast composed of small glands lacking myoepithelial cells and lined by S100-positive, oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative epithelial cells.
Microglandular adenosis (MGA) is a rare proliferative lesion of the breast composed of small glands lacking myoepithelial cells and lined by S100-positive, oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative epithelial cells.
Recent studies have suggested that MGA may be a non-obligate precursor of invasive carcinomas that are negative for hormone receptors and lack HER-2 overexpression (triple-negative phenotype).
The aim of this study was to determine whether MGA is clonal and whether it harbours chromosomal aberrations similar to those found in matched invasive ductal carcinoma of no special type (IDC-NST).
In the MGA/AMGA associated with TNBC lacking TP53 mutations, somatic mutations affecting PI3K pathway-related genes (eg PTEN, PIK3CA, and INPP4B) and tyrosine kinase receptor signalling-related genes (eg ERBB3 and FGFR2) were identified.
To investigate the possibility of such a transition, we studied 17 cases of MGA or atypical MGA some of which had given rise to carcinoma in situ (CIS) and/or invasive ductal carcinoma using the reticulin stain, immunohistochemistry (S-100, p63, Ki-67, and p53), and a molecular approach involving microdissection and high-resolution comparative genomic hybridization and MYC chromogenic in situ hybridization.
In the MGA/AMGA associated with TNBC lacking TP53 mutations, somatic mutations affecting PI3K pathway-related genes (eg PTEN, PIK3CA, and INPP4B) and tyrosine kinase receptor signalling-related genes (eg ERBB3 and FGFR2) were identified.
In the MGA/AMGA associated with TNBC lacking TP53 mutations, somatic mutations affecting PI3K pathway-related genes (eg PTEN, PIK3CA, and INPP4B) and tyrosine kinase receptor signalling-related genes (eg ERBB3 and FGFR2) were identified.
Loss of heterozygosity/allelic imbalance was detected in six of 17 cases of apocrine adenosis; three of 12 (25%) informative cases at 1p (MYCL1), two of seven (28.6%) at 11q (INT2), one of three (33.3%) at 13q (D13S267), two of 12 (16.7%) at 16q (D16S539), and two of 10 (20%) at 17q (D17S250).
Whole sections of primary breast ACC (n=11), collagenous spherulosis (CS; n=7), and microglandular adenosis (MGA; n=5) and tissue microarrays containing 16 basal-like, triple-negative breast carcinomas (TNBC) were labeled for MYB by IHC and underwent MYB fluorescence in situ hybridization using a break-apart probe.
The relationship between microglandular adenosis and malignancy and the association between BRCA 1 and proliferative benign disorders are also discussed.
Recurrent (n=2) somatic mutations restricted to microglandular adenosis or acinic cell carcinomas included those affecting PTEN and MED12 or ERBB4, respectively.