Navigating prognostic strategies for GH- and PRL-secreting pituitary neuroendocrine tumors: key insights from a clinicopathological study
The classification of pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, has progressed significantly since 2004. The PitNET lineage now serves as the foundation of the classification. We investigated the prognostic value of clinicopathological markers in a cohort of patien...
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| Vydáno v: | Frontiers in endocrinology (Lausanne) Ročník 16; s. 1541514 |
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10.04.2025
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| Abstract | The classification of pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, has progressed significantly since 2004. The PitNET lineage now serves as the foundation of the classification. We investigated the prognostic value of clinicopathological markers in a cohort of patients diagnosed with acromegaly and prolactinomas who underwent transsphenoidal tumor resection.
A total of 50 patients (45 patients with confirmed acromegaly and 5 with prolactinomas) in evidence at 'C. I. Parhon National Institute of Endocrinology (Pituitary and Neuroendocrine Pathology Department, Bucharest, Romania), who underwent tumor resection between 2010 and 2023, was recruited, with a median follow-up time of 7.02 years (IQR: 3-10). Surgical samples were stained for anterior pituitary hormones, ki-67 labeling index, CAM 5.2 expression, and the following transcription factors (TFs): steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (PIT-1). Additionally, somatostatin receptor 5 (SSTR 5) and 2 (SSTR 2) expression was evaluated in all patients.
Based on the 2022 WHO classification, the majority of cases were PIT-1 lineage tumors (n=40, 72.7%), followed by TPIT-lineage (n=4, 7.3%), and SF-1 lineage (n=3, 5.5%) and 14.5% (n=4) were classified as tumors with no distinct cell lineage (NDCL). In the multivariate Cox regression analysis, the postoperative GH value was independently associated with the outcome (HR 1.042, 95% CI 1.004-1.081, p=0.030), as well as the postoperative PRL value (HR 1.95% CI 1,1.001, p=0.019), the ki-67 labelling index (HR 2.43, 95% CI 1.109-5.330, p=0.026). Other factors associated as well with the success of the treatment were the postoperative tumor diameter (HR 1.038 95% CI 0.997-1.080, p=0.068) and the expression of SSTRs 2 and 5. Combining the four parameters, ki-67, SSTR 2, SSTR 5, GH, IGF-1 and the maximal tumor diameter (postoperative values), we established a prediction model with an AUC of 0.924 and relatively high sensitivity and specificity.
A clear classification system that can guide clinical and neurosurgical management of patients with GH- and PRL-secreting PitNETs is not currently available, but certain clinicopathological factors can be used to predict patient prognosis. In our study, somatostatin receptor expression, ki-67, and postoperative values of GH and IGF-1, as well as the maximal postoperative tumor diameter, were the strongest predictors of outcome. |
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| AbstractList | The classification of pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, has progressed significantly since 2004. The PitNET lineage now serves as the foundation of the classification. We investigated the prognostic value of clinicopathological markers in a cohort of patients diagnosed with acromegaly and prolactinomas who underwent transsphenoidal tumor resection.
A total of 50 patients (45 patients with confirmed acromegaly and 5 with prolactinomas) in evidence at 'C. I. Parhon National Institute of Endocrinology (Pituitary and Neuroendocrine Pathology Department, Bucharest, Romania), who underwent tumor resection between 2010 and 2023, was recruited, with a median follow-up time of 7.02 years (IQR: 3-10). Surgical samples were stained for anterior pituitary hormones, ki-67 labeling index, CAM 5.2 expression, and the following transcription factors (TFs): steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (PIT-1). Additionally, somatostatin receptor 5 (SSTR 5) and 2 (SSTR 2) expression was evaluated in all patients.
Based on the 2022 WHO classification, the majority of cases were PIT-1 lineage tumors (n=40, 72.7%), followed by TPIT-lineage (n=4, 7.3%), and SF-1 lineage (n=3, 5.5%) and 14.5% (n=4) were classified as tumors with no distinct cell lineage (NDCL). In the multivariate Cox regression analysis, the postoperative GH value was independently associated with the outcome (HR 1.042, 95% CI 1.004-1.081, p=0.030), as well as the postoperative PRL value (HR 1.95% CI 1,1.001, p=0.019), the ki-67 labelling index (HR 2.43, 95% CI 1.109-5.330, p=0.026). Other factors associated as well with the success of the treatment were the postoperative tumor diameter (HR 1.038 95% CI 0.997-1.080, p=0.068) and the expression of SSTRs 2 and 5. Combining the four parameters, ki-67, SSTR 2, SSTR 5, GH, IGF-1 and the maximal tumor diameter (postoperative values), we established a prediction model with an AUC of 0.924 and relatively high sensitivity and specificity.
A clear classification system that can guide clinical and neurosurgical management of patients with GH- and PRL-secreting PitNETs is not currently available, but certain clinicopathological factors can be used to predict patient prognosis. In our study, somatostatin receptor expression, ki-67, and postoperative values of GH and IGF-1, as well as the maximal postoperative tumor diameter, were the strongest predictors of outcome. BackgroundThe classification of pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, has progressed significantly since 2004. The PitNET lineage now serves as the foundation of the classification. We investigated the prognostic value of clinicopathological markers in a cohort of patients diagnosed with acromegaly and prolactinomas who underwent transsphenoidal tumor resection.MethodsA total of 50 patients (45 patients with confirmed acromegaly and 5 with prolactinomas) in evidence at ‘C. I. Parhon National Institute of Endocrinology (Pituitary and Neuroendocrine Pathology Department, Bucharest, Romania), who underwent tumor resection between 2010 and 2023, was recruited, with a median follow-up time of 7.02 years (IQR: 3–10). Surgical samples were stained for anterior pituitary hormones, ki-67 labeling index, CAM 5.2 expression, and the following transcription factors (TFs): steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (PIT-1). Additionally, somatostatin receptor 5 (SSTR 5) and 2 (SSTR 2) expression was evaluated in all patients.ResultsBased on the 2022 WHO classification, the majority of cases were PIT-1 lineage tumors (n=40, 72.7%), followed by TPIT-lineage (n=4, 7.3%), and SF-1 lineage (n=3, 5.5%) and 14.5% (n=4) were classified as tumors with no distinct cell lineage (NDCL). In the multivariate Cox regression analysis, the postoperative GH value was independently associated with the outcome (HR 1.042, 95% CI 1.004–1.081, p=0.030), as well as the postoperative PRL value (HR 1.95% CI 1,1.001, p=0.019), the ki-67 labelling index (HR 2.43, 95% CI 1.109–5.330, p=0.026). Other factors associated as well with the success of the treatment were the postoperative tumor diameter (HR 1.038 95% CI 0.997–1.080, p=0.068) and the expression of SSTRs 2 and 5. Combining the four parameters, ki-67, SSTR 2, SSTR 5, GH, IGF-1 and the maximal tumor diameter (postoperative values), we established a prediction model with an AUC of 0.924 and relatively high sensitivity and specificity.ConclusionA clear classification system that can guide clinical and neurosurgical management of patients with GH- and PRL-secreting PitNETs is not currently available, but certain clinicopathological factors can be used to predict patient prognosis. In our study, somatostatin receptor expression, ki-67, and postoperative values of GH and IGF-1, as well as the maximal postoperative tumor diameter, were the strongest predictors of outcome. The classification of pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, has progressed significantly since 2004. The PitNET lineage now serves as the foundation of the classification. We investigated the prognostic value of clinicopathological markers in a cohort of patients diagnosed with acromegaly and prolactinomas who underwent transsphenoidal tumor resection.BackgroundThe classification of pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, has progressed significantly since 2004. The PitNET lineage now serves as the foundation of the classification. We investigated the prognostic value of clinicopathological markers in a cohort of patients diagnosed with acromegaly and prolactinomas who underwent transsphenoidal tumor resection.A total of 50 patients (45 patients with confirmed acromegaly and 5 with prolactinomas) in evidence at 'C. I. Parhon National Institute of Endocrinology (Pituitary and Neuroendocrine Pathology Department, Bucharest, Romania), who underwent tumor resection between 2010 and 2023, was recruited, with a median follow-up time of 7.02 years (IQR: 3-10). Surgical samples were stained for anterior pituitary hormones, ki-67 labeling index, CAM 5.2 expression, and the following transcription factors (TFs): steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (PIT-1). Additionally, somatostatin receptor 5 (SSTR 5) and 2 (SSTR 2) expression was evaluated in all patients.MethodsA total of 50 patients (45 patients with confirmed acromegaly and 5 with prolactinomas) in evidence at 'C. I. Parhon National Institute of Endocrinology (Pituitary and Neuroendocrine Pathology Department, Bucharest, Romania), who underwent tumor resection between 2010 and 2023, was recruited, with a median follow-up time of 7.02 years (IQR: 3-10). Surgical samples were stained for anterior pituitary hormones, ki-67 labeling index, CAM 5.2 expression, and the following transcription factors (TFs): steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (PIT-1). Additionally, somatostatin receptor 5 (SSTR 5) and 2 (SSTR 2) expression was evaluated in all patients.Based on the 2022 WHO classification, the majority of cases were PIT-1 lineage tumors (n=40, 72.7%), followed by TPIT-lineage (n=4, 7.3%), and SF-1 lineage (n=3, 5.5%) and 14.5% (n=4) were classified as tumors with no distinct cell lineage (NDCL). In the multivariate Cox regression analysis, the postoperative GH value was independently associated with the outcome (HR 1.042, 95% CI 1.004-1.081, p=0.030), as well as the postoperative PRL value (HR 1.95% CI 1,1.001, p=0.019), the ki-67 labelling index (HR 2.43, 95% CI 1.109-5.330, p=0.026). Other factors associated as well with the success of the treatment were the postoperative tumor diameter (HR 1.038 95% CI 0.997-1.080, p=0.068) and the expression of SSTRs 2 and 5. Combining the four parameters, ki-67, SSTR 2, SSTR 5, GH, IGF-1 and the maximal tumor diameter (postoperative values), we established a prediction model with an AUC of 0.924 and relatively high sensitivity and specificity.ResultsBased on the 2022 WHO classification, the majority of cases were PIT-1 lineage tumors (n=40, 72.7%), followed by TPIT-lineage (n=4, 7.3%), and SF-1 lineage (n=3, 5.5%) and 14.5% (n=4) were classified as tumors with no distinct cell lineage (NDCL). In the multivariate Cox regression analysis, the postoperative GH value was independently associated with the outcome (HR 1.042, 95% CI 1.004-1.081, p=0.030), as well as the postoperative PRL value (HR 1.95% CI 1,1.001, p=0.019), the ki-67 labelling index (HR 2.43, 95% CI 1.109-5.330, p=0.026). Other factors associated as well with the success of the treatment were the postoperative tumor diameter (HR 1.038 95% CI 0.997-1.080, p=0.068) and the expression of SSTRs 2 and 5. Combining the four parameters, ki-67, SSTR 2, SSTR 5, GH, IGF-1 and the maximal tumor diameter (postoperative values), we established a prediction model with an AUC of 0.924 and relatively high sensitivity and specificity.A clear classification system that can guide clinical and neurosurgical management of patients with GH- and PRL-secreting PitNETs is not currently available, but certain clinicopathological factors can be used to predict patient prognosis. In our study, somatostatin receptor expression, ki-67, and postoperative values of GH and IGF-1, as well as the maximal postoperative tumor diameter, were the strongest predictors of outcome.ConclusionA clear classification system that can guide clinical and neurosurgical management of patients with GH- and PRL-secreting PitNETs is not currently available, but certain clinicopathological factors can be used to predict patient prognosis. In our study, somatostatin receptor expression, ki-67, and postoperative values of GH and IGF-1, as well as the maximal postoperative tumor diameter, were the strongest predictors of outcome. |
| Author | Nastase, Valeria Nicoleta Raica, Marius Dobre, Ramona Dumitriu-Stan, Roxana-Ioana Molnar, Catalina Gabriela Burcea, Iulia-Florentina Ceausu, Raluca Amalia Poiana, Catalina |
| AuthorAffiliation | 2 Deparment of Endocrinology I, ‘C. I. Parhon National Institute of Endocrinology , Bucharest , Romania 4 Angiogenesis Research Centre, ‘Victor Babes’ University of Medicine and Pharmacy , Timisoara , Romania 3 Department of Microscopic Morphology/Histology, ‘Victor Babes’ University of Medicine and Pharmacy , Timisoara , Romania 1 Department of Endocrinology, ‘Carol Davila’ University of Medicine and Pharmacy , Bucharest , Romania 5 Deparment of Internal Medicine, Florida Atlantic University , Boca Raton, FL , United States |
| AuthorAffiliation_xml | – name: 5 Deparment of Internal Medicine, Florida Atlantic University , Boca Raton, FL , United States – name: 2 Deparment of Endocrinology I, ‘C. I. Parhon National Institute of Endocrinology , Bucharest , Romania – name: 4 Angiogenesis Research Centre, ‘Victor Babes’ University of Medicine and Pharmacy , Timisoara , Romania – name: 1 Department of Endocrinology, ‘Carol Davila’ University of Medicine and Pharmacy , Bucharest , Romania – name: 3 Department of Microscopic Morphology/Histology, ‘Victor Babes’ University of Medicine and Pharmacy , Timisoara , Romania |
| Author_xml | – sequence: 1 givenname: Roxana-Ioana surname: Dumitriu-Stan fullname: Dumitriu-Stan, Roxana-Ioana – sequence: 2 givenname: Iulia-Florentina surname: Burcea fullname: Burcea, Iulia-Florentina – sequence: 3 givenname: Ramona surname: Dobre fullname: Dobre, Ramona – sequence: 4 givenname: Valeria Nicoleta surname: Nastase fullname: Nastase, Valeria Nicoleta – sequence: 5 givenname: Raluca Amalia surname: Ceausu fullname: Ceausu, Raluca Amalia – sequence: 6 givenname: Catalina Gabriela surname: Molnar fullname: Molnar, Catalina Gabriela – sequence: 7 givenname: Marius surname: Raica fullname: Raica, Marius – sequence: 8 givenname: Catalina surname: Poiana fullname: Poiana, Catalina |
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| Keywords | 2022 WHO classification acromegaly prognostic factors prolactinoma pituitary tumor |
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| Snippet | The classification of pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, has progressed significantly since 2004. The PitNET lineage... BackgroundThe classification of pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, has progressed significantly since 2004. The... |
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| SubjectTerms | 2022 WHO classification acromegaly Acromegaly - metabolism Acromegaly - pathology Acromegaly - surgery Adult Aged Endocrinology Female Follow-Up Studies Growth Hormone-Secreting Pituitary Adenoma - metabolism Growth Hormone-Secreting Pituitary Adenoma - pathology Growth Hormone-Secreting Pituitary Adenoma - surgery Human Growth Hormone - metabolism Humans Male Middle Aged Neuroendocrine Tumors - diagnosis Neuroendocrine Tumors - metabolism Neuroendocrine Tumors - pathology Neuroendocrine Tumors - surgery Pituitary Neoplasms - diagnosis Pituitary Neoplasms - metabolism Pituitary Neoplasms - pathology Pituitary Neoplasms - surgery pituitary tumor Prognosis prognostic factors prolactinoma Prolactinoma - metabolism Prolactinoma - pathology Prolactinoma - surgery |
| Title | Navigating prognostic strategies for GH- and PRL-secreting pituitary neuroendocrine tumors: key insights from a clinicopathological study |
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