Ki-67 index as an ancillary tool in the differential diagnosis of proliferative endometrial lesions with secretory change

"Secretory change" can accompany a variety of proliferative endometrial lesions, ranging from hyperplasia to carcinoma. It is characterized by subnuclear or supranuclear vacuolization, mimicking early secretory endometrium (SEM). As an additional diagnostic challenge, mitotic activity and cytologic atypia are often low in hyperplastic lesions with secretory change. As mitotic activity in lesions with secretory change is decreased, the mitotic index may not be useful to distinguish SEM with glandular crowding from hyperplasia with secretory change. We therefore hypothesized that Ki-67 immunohistochemistry, an alternative marker of proliferative activity, might be useful in this setting. Forty-four endometrial lesions with secretory change and 30 controls were stained for Ki-67. Three "hot spot" areas per case were photographed and 200 to 300 cells were manually counted to obtain the ratio of Ki-67-positive cells versus total cells. A second pathologist performed an independent review of the same preselected fields and estimates without preselection. There was an incremental increase in the Ki-67 index from 2.6% in SEM to 17% in nonatypical hyperplasia, 36% in atypical hyperplasia, and 60% in endometrial carcinoma. The Ki-67 index for SEM was significantly (P<0.01) lower than hyperplastic lesions and carcinoma with secretory change. Similar, statistically significant results were obtained by independent estimates of Ki-67 immunopositivity. In the setting of secretory morphology, the Ki-67 index was highly sensitive and specific (>90%) for the differential diagnosis of SEM with crowding versus nonatypical hyperplasia, atypical hyperplasia, and endometrial carcinoma. In summary, the Ki-67-labeling index is a useful technique to distinguish SEM with crowding, an exaggerated physiological condition, from cancer precursors.