Quantitative Ki-67 Index as an Ancillary Tool in the Differential Diagnosis of Endometrial Lesions with Secretory Change
Grzegorz T Gurda, Alexander S Baras, Ie-Ming Shih, Robert J Kurman. Johns Hopkins Hospital, Baltimore, MD
Background: “Secretory change” or “secretory metaplasia” in various endometrial lesions, including hyperplasia and carcinoma, is characterized by vacuolization simulating normal secretory endometrium. Normal secretory endometrium (SEM) can display considerable crowding, therefore, secretory change in hyperplasia can be difficult to distinguish from SEM with glandular crowding. Proliferative activity drops precipitously in the early secretory phase; this led us to hypothesize that in contrast to SEM, hyperplastic lesions with secretory change would show significantly greater proliferation. The aim of this study was to evaluate Ki-67 labeling to confirm this hypothesis.
Design: 52 endometrial lesions with secretory features, along with 24 controls were stained for H&E and Ki-67. Three fields with hot spots of Ki-67 were photographed at 200X with each field comprising 4-22 glands and a total of ∼500-1000 cells. 200-300 cells per field were manually counted, Ki-67 positive cells were recorded and reported as a percentage (GTG); a second pathologist (AJB) performed an independent, review of the H&E slides of the same pre-selected fields as well as another estimate of hot spots within entirely imaged slides.
Results: There was an incremental increase in the Ki-67 proliferation index for endometrial lesions with secretory change that paralleled the progression of hyperplasia to endometrial carcinoma. There was no significant change in Ki-67 index between secretory endometrium and focal glandular crowding, but a significant increase compared to hyperplasia with or without cytologic atypia, and endometrial carcinoma. Similar findings were observed by two independent H&E estimates.
Conclusions: Ki-67 labeling in SEM was close to zero and increased incrementally in hyperplasia, atypical hyperplasia and endometrial carcinoma. The difference in between SEM and hyperplasia was significant (p<0.01) supporting the use of this technique in differentiating these lesions from hyperplasia.
|Ki-67 positivity:||Interval Endometrium (pos control)||Secretory Endometrium (neg control)||Focal Glandular Crowding||Hyperplasia w/o atypia||Hyperplasia with atypia||Endometrial Carcinoma|
|Manual Count (Gold Standard)||55±21%||1.4±1.3%||2.3±1.3% NS||18±7.9% **||31±10% **||57±21% NS|
|Estimate (pre-selected)||70±28%||0.8±1.9%||1.4±2.4% NS||15±16 % **||36±26% NS||86±14% **|
|Estimate (whole slides)||64±24%||0.6±0.7%||0.9±0.7% NS||11±12 % **||16±7.2% NS||72±35% **|
|Age (±SD)||41±4.6 yo||42±5.8 yo||42±5.0yo||49±15yo||49±13yo||58±12yo|
|# cases (n)||12||12||8||24||10||10|