[1077] Frequent Loss of Progesterone Response Competence in Isolated Non-Cycling Glands of Normal Secretory Endometrium.

Brooke E Lane, Nicolas M Monte, Julia Elvin, George L Mutter. Brigham and Women's Hospital, Boston, MA

Background: Small numbers of isolated non-cycling (atrophic, proliferative, or very poorly developed secretory) endometrial glands are commonly (45%) seen within the surface layer of progesterone-exposed normal secretory endometrium. We hypothesize that these glands have either lost the progesterone receptor, or developed downstream defects elsewhere in the progesterone response pathway. We here compare expression of a panel of progesterone response genes in these outlier glands to those in background secretory glands.
Design: 20 cases of normal, mid-secretory (23-24 days) endometrial curettings with two or more outlier non-secretory glands on H&E stain were immunostained for mitotic activity (MIB1), and three makers normally downregulated in response to progestins (estrogen receptor,”ER”, progesterone receptor,”PR”, and PAX2). For each marker, outlier glands were scored as high expressors (indicating defective progesterone associated downregulation) or normal expressors at the low level of the secretory background.

All or most outlier glands maintained high expression of ER, PR or PAX2 in 83% (15/18), 95% (18/19), and 84% (16/19) of informative cases, respectively, when compared to the diminished levels in background secretory endometrium. Increases in outlier gland mitotic activity (MIB1) were seen in 55% (11/20) of cases. Figure 1 shows marker results for outlier (arrows) compared to adjacent normal (asterisk) background glands.
Conclusions: Acquisition of hormonal incompetence is a common event in small numbers of endometrial glands, which present on routine stains as a dyssynchronous minor element in an otherwise normal secretory endometrium. Outlier glands maintain high levels of ER, PR, and PAX2 expression, in contrast to the low levels in normal background. Affected glands have an increase in mitotic activity. This cannot be explained simply by loss of the progesterone receptor itself, but rather reflects a defective progesterone response within affected glands. The etiology is unknown, but might be explained by a low frequency of inactivating events (mutation, deletion) occurring within the progesterone response cascade during cyclic endometrial gland regeneration.
Category: Gynecologic & Obstetrics

Monday, February 28, 2011 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 132, Monday Morning


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