Flat Epithelial Atypia of the Breast Immunohistochemical Evaluation of Estrogen Receptor(ER) and cyclin DI protein Expression.
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Introduction: Flat epithelial atypia (PEA) is a descriptive term that encompasses lesions of breast terminal duct lobular unit in which variably dilated acini with cyst formation are lined by one to several cell layers display low grade cytologic atypia. It is considered to be one of earlier premalignant breast lesions. The cyclin DI is known to play an important role in the Gl/S check point of the cell cycle and its overexpression has been correlated with progression of breast cancer. The estrogen receptor (ER) level determinate the proliferative activity of cells which could be bearing on the development of premalignant and malignant breast lesions. It has been postulated that the effect of cyclinD1 in cooperation with ER exert effects on mammary carcinogenesis. Aim of work: this work was aimed to determine the cyclinDI and ER expression in flat epithelial atypia and correlate with other premalignant and malignant breast lesions in order to evaluate the relationship between duct carcinoma and the presence of coexistent flat epithelial atypia which could provide insight into connection between both lesions. Materials and Methods: Paraffin blocks from 80 cases of breast lesions including 15 cases of ductal carcinoma in situ ( DCIS) , 30 cases of invasive duct carcinoma ('IDC) and 27 cases of flbrocystic disease of breast( FCD) with usual ductal hyperplasia( UDH) and 8 cases of atypical ductal hyperplasia ( ADH) were collected. Examination of serial stained H&E sections were carried out and the association between the presence of PEA and these lesions was determined. Immunohistochemistry has been used to assess cyclinD1 and ER expression in PEA and its relation to different breast lesions enclosing it Adjacent terminal duct lobular unit (TDLU) of normal breast tissue were analyzed and served as control. The relationship between cyclinD1 expression and differentiation of DCIS and IDC cases and the interrelationship between cyclinD1 expression and ER in this group of cases was examined. The expression of these markers in cases of atypical ductal hyperplasia (ADH) has been compared with the expression seen in PEA, DCIS, IDC and FCD. Results: Twelve cases of flat epithelial atypia was detected in association with following lesions as follow 6 cases with DCIS , 5 cases with IDC and one case with FCD but non was seen with ADH. Cases of duct carcinoma are of low grade category. CyclinD1 overexpression was observed in 8 /12(66.7%) cases of PEA, in10/15(66.7%) cases of DCIS, in 11/30(36.6%) cases of IDC and 1/8(12.5%) case ofADH. Overexpression was not observed in breast lobules (typel and type2/3) and FCD with usual ductal hyperplasia. PEA had cyclinD1 expression similar to that expressed by the lesion harboring it The overexpression of cyclinD1 in PEA lesions and in low grade DCIS was higher than that of ADH lesions and the difference was statistically significant (p<0.05). ER expression was observed in 12/12(100%) cases of PEA, in 11/15(73.3%) cases of DCIS, 20/30(66.7%) cases of IDC, 8/8(100%) cases of ADH and 16/18(88.9%) cases of breast lobule type 1. A positive ER expression was significantly associated with well differentiated DCIS and IDC (p<0.01). In invasive duct carcinoma, there was significant association between cyclinDI expression and both grade and ER status (p<0.01). This association in cases of DCIS was lacked (p=0.06). Conclusion: This study demonstrate that flat epithelial atypia represent a distinct lesion with consistent ER and cyclinD1 immunproflle matches with that of low grade ductal carcinoma in situ supporting the concept that flat epithelial atypia is neoplastic proliferation and it might be represent either precursor of 1 or the earliest morphologic manifestation of/034' grade DCLS as ire!! as being precursor to logv grade III(. The interaction between cyclinDI and ER overexpression has an important role in early development and progression of FEA lesion to low grade in situ and invasive ductal carcinoma. Also the gyclinD1 overexpression does not correlate with progression of breast cancer frong low to high grade. tyclind 1 overexpression could of help to differentiate ADH from low grade micropapillaty and cribrifOrm DCIS.