Abstract
BackgroundFlat epithelial atypia (FEA) of the breast is characterised by a few layers of mildly atypical luminal epithelial cells. Genetic changes found in ductal carcinoma in situ (DCIS) and invasive ductal breast cancer (IDC) are also found in FEA, albeit at a lower concentration. So far, miRNA expression changes associated with invasive breast cancer, like miR-21, have not been studied in FEA.MethodsWe performed miRNA in-situ hybridization (ISH) on 15 cases with simultaneous presence of normal breast tissue, FEA and/or DCIS and 17 additional cases with IDC. Expression of the miR-21 targets PDCD4, TM1 and PTEN was investigated by immunohistochemistry.ResultsTwo out of fifteen cases showed positive staining for miR-21 in normal breast ductal epithelium, seven out of fifteen cases were positive in the FEA component and nine out of twelve cases were positive in the DCIS component. A positive staining of miR-21 was observed in 15 of 17 IDC cases. In 12 cases all three components were present in one tissue block and an increase of miR-21 from normal breast to FEA and to DCIS was observed in five cases. In three cases the FEA component was negative, whereas the DCIS component was positive for miR-21. In three other cases, normal, FEA and DCIS components were negative for miR-21 and in the last case all three components were positive. Overall we observed a gradual increase in percentage of miR-21 positive cases from normal, to FEA, DCIS and IDC. Immunohistochemical staining for PTEN revealed no obvious changes in staining intensities in normal, FEA, DCIS and IDC. Cytoplasmic staining of PDCD4 increased from normal to IDC, whereas, the nuclear staining decreased. TM1 staining decreased from positive in normal breast to negative in most DCIS and IDC cases. In FEA, the staining pattern for TM1 was similar to normal breast tissue.ConclusionUpregulation of miR-21 from normal ductal epithelial cells of the breast to FEA, DCIS and IDC parallels morphologically defined carcinogenesis. No clear relation was observed between the staining pattern of miR-21 and its previously reported target genes.
Highlights
Flat epithelial atypia (FEA) of the breast is characterised by a few layers of mildly atypical luminal epithelial cells
Using Fisher exact test, we found that the percentage of miR-21 positive cases was significantly higher in invasive ductal breast cancer (IDC) and ductal carcinoma in situ (DCIS) compared with normal breast tissue
Our results showed that there was an obvious decrease in the percentage of positive cases for Tropomyosin 1 (TM1) with progression, i.e. the majority of cases being positive in both normal and FEA and a minority of cases being positive in IDC
Summary
Flat epithelial atypia (FEA) of the breast is characterised by a few layers of mildly atypical luminal epithelial cells. Genetic changes found in ductal carcinoma in situ (DCIS) and invasive ductal breast cancer (IDC) are found in FEA, albeit at a lower concentration. Flat epithelial atypia (FEA) was first proposed as an entity in 2003 in the World Health Organization classification of tumours of the breast [1]. It is defined as an intraductal neoplasm, characterized by the replacement of original epithelial cells by a single or 3–5 thick layer of mildly atypical cells with loss of polarization. For that reason it is interesting to study whether FEA has to be regarded as a true premalignant lesion or only as an indolent precursor lesion, with or without relationship with DCIS
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