Cytokeratin 19 expression in normal endometrium and in low-grade endometrioid adenocarcinoma of the endometrium.

The low-molecular-weight cytokeratin (CK) protein CK19 has been shown to have diagnostic use and prognostic significance in some types of human malignancy, but little is known of its distribution in normal endometrial mucosa or in endometrial endometrioid adenocarcinoma. However, we had observed that CK19 appeared to selectively label invasive tumor areas showing microcystic, elongated, and fragmented ("MELF") changes. Therefore, CK19 expression was assessed in 15 hysterectomy specimens showing normal proliferative, secretory, or atrophic endometrial appearances, and in 26 endometrioid adenocarcinoma cases with areas of MELF-type invasion. Normal endometrial glands were usually CK19 positive; however, there was more consistent expression in the functional layer, whereas basal zone epithelium was typically only focally stained. Proliferative epithelium frequently showed basal and apical cytoplasmic accentuation of staining. Endometrial carcinomas were also CK19 positive, but in most cases there was a distinct zonal pattern of expression with strong staining only in the central aspects of the larger tumor glands and weak-to-absent staining in peripheral glandular areas. In contrast, MELF-type tumor epithelium was consistently and strongly CK19 positive even when the adjacent "conventional"-type tumor glands were not stained. Intravascular tumor cells were also highlighted, including 2 cases in which this feature was not identified on hematoxylin and eosin stains. Thus CK19 immunohistochemistry was useful in showing the extent of myometrial invasion and subtle foci of lympho-vascular space invasion. Further studies are required to determine the mechanism and biologic significance of localized alterations in CK19 expression within endometrial neoplasms.

Correlation between invasive pattern and immunophenotypic alterations in endocervical adenocarcinoma.

AIMS: To assess the immunophenotypic changes associated with epithelial-mesenchymal transition (EMT) in endocervical adenocarcinoma, and correlate the findings with tumour morphology including growth pattern. METHODS AND RESULTS: Twenty-seven endocervical adenocarcinomas were studied using a panel of immunohistochemical markers to vimentin, cyclin D1, E-cadherin, beta-catenin, p16 protein and cytokeratin 7. There were 24 moderately differentiated and three poorly differentiated tumours. Fourteen of the moderately differentiated carcinomas showed a focal infiltrative component, typically towards the deep tumour margin (invasive front), comprising attenuated glands, small cell clusters and single cells. These foci typically showed cytological alteration including loss of cellular polarity and cytoplasmic eosinophilia, while immunohistochemistry demonstrated reduced cell membrane E-cadherin and beta catenin labelling, and expression of cyclin D1 and, in some cases, vimentin. Similar immunophenotypic changes were focally observed at the deep aspect of some larger 'conventional' tumour glands. No consistent changes were observed in the poorly differentiated carcinomas. CONCLUSIONS: Endocervical adenocarcinomas that demonstrate an infiltrative growth pattern show immunophenotypic changes consistent with EMT. Frequently, these are accompanied by a morphological alteration in the tumour cells and the changes exhibit a specific micro-anatomical distribution. Epithelial-mesenchymal transition may represent an important mechanism in the progression of some endocervical neoplasms.