Stewart C J R, Crook M L & Doherty D A
(2010) Histopathology 57, 46–54
Micro‐anatomical variation in cellular proliferation in endometrial adenocarcinoma, and inverse correlation between Ki67 and cytokeratin 7 expressionAims:  To investigate micro‐anatomical variations in proliferative activity within uterine endometrioid adenocarcinoma with particular emphasis on tumour areas comprising microcystic, elongated and fragmented (‘MELF’) glands.Methods and results:  Ki67 immunoreactivity was assessed in 29 low‐grade endometrial adenocarcinomas specifically comparing conventional tumour glands and areas exhibiting MELF‐type alteration. Furthermore, since Ki67 expression differed between the peripheral and central aspects of larger neoplastic glands, these micro‐anatomical compartments were assessed separately using a semiquantitative scoring system. Most MELF‐type tumour elements were negative for Ki67 or showed only rare (<5% cells) positivity. In contrast, peripheral conventional tumour glands showed prominent Ki67 labelling, but this was significantly reduced in central glandular areas. An inverse correlation between Ki67 and cytokeratin (CK) 7 expression was noted in many tumours.Conclusions:  Endometrial adenocarcinomas show micro‐anatomical variations in Ki67 expression and this is often inversely correlated with CK7 immunoreactivity. MELF‐type tumour elements show minimal proliferative activity, a finding that initially appears unexpected for areas of purported active invasion. However, an inverse correlation between cell division and local invasion has been demonstrated in other malignancies, notably during epithelial–mesenchymal transition, and this may reflect a reversible alteration in cellular activity during neoplastic progression.