Estrogen Receptorα, a Sex-Dependent Predictor of Aggressiveness in Nonfunctioning Pituitary Adenomas: SSTR and Sex Hormone Receptor Distribution in NFPA

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Abstract

Context:

Nonfunctioning pituitary adenomas (NFPAs) are fairly common and require a multidisciplinary approach. Reliable markers of a clinically aggressive course are lacking. Medical treatment is not available, and transsphenoidal surgery is the preferred primary treatment.

Objective:

We aimed to characterize the somatostatin, estrogen, and progesterone receptor distribution for NFPAs and compare it with factors of tumor aggressiveness.

Design:

Tumor samples for immunohistochemistry (n = 145) and quantitative reverse transcription polymerase chain reaction (n = 106) analyses of somatostatin receptor (SSTR) 1, SSTR2, SSTR3, SSTR5, estrogen receptor α (ERα), and progesterone receptor (PR) were measured by immunoreactive score (IRS) and messenger RNA relative quantity and retrospectively compared with variables of aggressiveness.

Setting:

All patients were operated at the same tertiary referral center.

Participants:

A total of 164 patients with NFPA and tumor tissue from the primary operation were included.

Results:

SSTR3 was expressed abundantly by immunohistochemistry in all NFPAs. The IRS of ERα correlated with that of SSTR2 in male patients only (males, P < 0.001; females, P = 0.8). Low ERα level was linked to a higher reintervention rate (P = 0.001) and earlier reintervention (P = 0.004) in male patients only (females, P = 0.95 and P = 0.65, respectively). Absence of ERα together with age provided a good prediction model for reintervention in male patients with gonadotroph adenomas.

Conclusions:

SSTR3 is expressed abundantly in NFPAs and is therefore a possible target for medical treatment. Absence of ERα together with young age may predict tumor recurrence in groups of NFPAs. Further validation in systematic prospective studies is needed.

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