Immunodetectable cyclin D-1 is associated with oestrogen receptor but not Ki67 in normal, cancerous and precancerous breast lesions

Cyclin D-1 is associated with cell cycle regulation and has more recently b een shown to stimulate the transcriptional functions of the oestrogen recep tor (ER). Furthermore, in normal breast there is a negative association bet ween expression of ER and the proliferation marker Ki67 indicating that eit her ER positive cells are non-dividing or that the receptor is down-regulat ed as cells enter cycle. This important relationship breaks down in many ER -positive cancers and precancerous breast lesions where the receptor is oft en detected on proliferating cells. The aims of the present study were to d etermine the interplay between ER, Ki67 and cyclin D-1 in individual cells within the spectrum of human breast lesions ranging from normal to invasive carcinoma by using dual staining immunofluorescence. We found that in norm al breast there was a strong positive association between ER and cyclin D-1 expression. In contrast there was a strong negative association between cy clin D-1 and Ki67 expression. Similar findings were seen for the other prec ancerous and cancerous breast lesions. Thus immunodetectable cyclin D-1 wit hin individual cells does not appear to be associated with cell cycle progr ession in the benign or malignant breast but instead may have important int eractions with ER. (C) 2001 Cancer Research Campaign.