Overexpression of mdm2 and p53 and association with progesterone receptor expression in benign meningiomas.
The progesterone receptor is frequently found expressed in meningiomas at robust levels. As several studies of breast and endometrial tumors have shown an inverse correlation between progesterone receptor expression and p53 overexpression, we sought to determine if a similar relationship existed in meningiomas. As p53 may also be inactivated by the overexpression of mdm2, we examined a cohort of 90 benign meningiomas immunohistochemically for the presence of the progesterone receptor as well as overexpression of p53 and mdm2. The progesterone receptor was detected in 67% (61/90) of cases, while p53 and mdm2 overexpression were detected in 14% (13/90) and 46% (42/90) of cases, respectively. An absolute correlation was observed between the overexpression of nuclear mdm2 and overexpression of the progesterone receptor, with nuclear mdm2 overexpression being confined to progesterone receptor-positive tumors (P = 0.001). While p53 overexpression was not associated with progesterone receptor expression, a combination of mdm2 overexpression and/or p53 overexpression was significantly associated with the presence of the progesterone receptor (P = 0.025). These results suggest the existence of a novel relationship between p53 (and its regulatory control) and the presence of the progesterone receptor and, as such, may have fundamental consequences in developing progesterone receptor-targeted therapies for meningiomas.
Das
Asha
A
Tan
Wan-Loo
WL
Teo
Jennifer
J
Smith
Duncan R
DR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism*; D008579:Meningioma / Q000378:metabolism*; D008875:Middle Aged; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051736:Proto-Oncogene Proteins c-mdm2; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2