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. 2023 Nov 10;24(22):16162.
doi: 10.3390/ijms242216162.

The Value of ER∝ in the Prognosis of GH- and PRL-Secreting PitNETs: Clinicopathological Correlations

Roxana-Ioana Dumitriu-Stan  1 , Iulia-Florentina Burcea  1   2 , Valeria Nicoleta Nastase  3   4 , Raluca Amalia Ceaușu  3   4 , Anda Dumitrascu  2 , Laurentiu Catalin Cocosila  5 , Alexandra Bastian  6   7 , Sabina Zurac  6   7 , Marius Raica  3   4 , Catalina Poiana  1   2
Affiliations

The Value of ER∝ in the Prognosis of GH- and PRL-Secreting PitNETs: Clinicopathological Correlations

Roxana-Ioana Dumitriu-Stan et al. Int J Mol Sci. .

Abstract

Pituitary neuroendocrine tumors (PitNETs) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Despite their benign evolution, in some cases, prolactin (PRL) and growth hormone (GH)-secreting PitNETs may have aggressive behavior. In this study, we investigated the potential predictive role of ER∝, alongside the clinicopathological classification of PitNETs (tumor diameter, tumor type, and tumor grade). A retrospective study was conducted with 32 consecutive cases of PRL- and mixed GH- and PRL-secreting PitNETs (5 patients with prolactinomas and 27 with acromegaly, among them, 7 patients with GH- and PRL- co-secretion) who underwent transsphenoidal intervention. Tumor specimens were histologically and immunohistochemical examined: anterior pituitary hormones, ki-67 labeling index, CAM 5.2, and ER∝; ER∝ expression was correlated with basal PRL levels at diagnosis (rho = 0.60, p < 0.01) and postoperative PRL levels (rho = 0.58, p < 0.001). In our study, the ER∝ intensity score was lower in female patients. Postoperative maximal tumor diameter correlated with Knosp grade (p = 0.02); CAM 5.2 pattern (densely/sparsely granulated/mixed densely and sparsely granulated) was correlated with postoperative PRL level (p = 0.002), and with ki-67 (p < 0.001). The IGF1 level at diagnosis was correlated with the postoperative GH nadir value in the oral glucose tolerance test (OGTT) (rho = 0.52, p < 0.05). Also, basal PRL level at diagnosis was correlated with postoperative tumor diameter (p = 0.63, p < 0.001). At univariate logistic regression, GH nadir in OGTT test at diagnostic, IGF1, gender, and invasion were independent predictors of remission for mixed GH- and PRL-secreting Pit-NETs; ER∝ can be used as a prognostic marker and loss of ER∝ expression should be considered a sign of lower differentiation and a likely indicator of poor prognosis. A sex-related difference can be considered in the evolution and prognosis of these tumors, but further studies are needed to confirm this hypothesis.

Keywords: GH- and PRL-secreting PitNET; PRL-secreting PitNET; estrogen receptor alpha; pituitary neuroendocrine tumor; prognostic factors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
A case of acromegaly due to a GH- and PRL-secreting PitNET with positive intense IHC staining for GH (+3, ×20 magnification) (A), PRL (+3, ×20 magnification) (B), ki-67 = 4% (×40 magnification), (C), ER∝ positive, and moderate intensity (+2, ×80 magnification) (D).
Figure 2
Figure 2
A case of resistant PRL-secreting PitNET with intense positive IHC staining for PRL (A), (×40 magnification); Cromophobe and acidophil tinctoriality, H&E staining (B) (×20 magnification); ER∝ intense positive (C) (+3, ×60 magnification); CAM 5.2, densely granulated pattern (D) (×40 magnification); ki-67 of 6% (E) (×20 magnification); T2-weighted magnetic resonance image sagittal plane—pituitary macroadenoma: 11/10/11 mm (postoperative) (F); T2-weighted magnetic resonance image coronal plane—pituitary macroadenoma (postoperative) (G).
Figure 2
Figure 2
A case of resistant PRL-secreting PitNET with intense positive IHC staining for PRL (A), (×40 magnification); Cromophobe and acidophil tinctoriality, H&E staining (B) (×20 magnification); ER∝ intense positive (C) (+3, ×60 magnification); CAM 5.2, densely granulated pattern (D) (×40 magnification); ki-67 of 6% (E) (×20 magnification); T2-weighted magnetic resonance image sagittal plane—pituitary macroadenoma: 11/10/11 mm (postoperative) (F); T2-weighted magnetic resonance image coronal plane—pituitary macroadenoma (postoperative) (G).
Figure 3
Figure 3
(a) ER∝ expression (positive/negative) was correlated with maximal postoperative tumor diameter (31.3 ± 19.4 mm versus 20 ± 9.7 mm, p = 0.03). (b) Average age by sex: female patients had a higher age compared to males (49 years old versus 37.8 years old). Patients not cured after surgery had an average age of 45.5 years old.
Figure 4
Figure 4
Preoperative GH level associated with the granulation pattern. The sparsely granulated pattern had a higher GH level than the densely granulated (18.2 ng/mL versus 7.6 ng/mL, p = 0.51).
Figure 5
Figure 5
(a) IGF1 at diagnosis and postoperative maximal tumor diameter association. (b) Serum prolactin concentration (ln) and patients’ age.
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