It is known that women with non-malignant breast diseases such as breast fibroadenoma (BFA) and fibrocystic mastopathy (FCM) have a potential risk of malignant transformation of the breast tissue (BT). BFA and FCM are not considered formally as precancerous diseases and only in rare cases can cancerate, but search for molecular and cellular markers that allow to form a risk group with increased probability of malignant transformation of BT in BFA and FCM, seems relevant.

OBJECTIVE

To study the expression of molecular and cellular markers associated with epithelial-mesenchymal transition, as well as with normal and cancerous stem cells of the mammary gland, in breast tissue in non-malignant breast diseases and invasive breast carcinoma of no special type.

MATERIALS AND METHODS

BT of patients with invasive breast carcinoma (IBC) (n=53), BFA (n=13), FCM (n=16) was studied. Expression of E-cadherin (CDH1), N-cadherin (CDH2), CD24 and CD29 was determined by immunohistochemical method.

RESULTS

It has been shown that IBC and BFA samples differ in degree of CDH1, CDH2, CD24, CD29 expression and CDH1/CDH2 ratio. IBC and FCM groups had differences in CDH2, CD24 expression and CDH1/CDH2 ratio. It has been established using ROC analysis that the models characterizing the differences between IBC and BFA are formed depending on the expression of CDH2 (AUC=0.967), CD24 (AUC=1.00) and CD29 (AUC=0.965); the differences between IBC and FCM samples are formed according to the expression of CDH2 (AUC=0.847), CD24 (AUC=0.988) and CD29 (AUC=0.662). Clustering of the integrated database of BT of patients with non-malignant breast diseases and IBC (on CDH1, CDH2, CD24, CD29, CDH1/CDH2) led to the formation of three large clusters: cluster 1 included indicators of patients IBC (95%), FCM (5%), BFA (0%); cluster 2 — IBC (73%), FCM (20%), BFA (7%); cluster 3 — IBC (0%), FCM (29%), BFA (71%).

CONCLUSION

The obtained data allow to form a methodological basis for the detection of malignant transformation risk in patients with benign mammary dysplasia depending on the expression of epithelial-mesenchymal transition markers and markers, associated with normal and cancerous stem cells of the mammary gland.