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Survivin: A Potential Marker of Resistance to Somatostatin Receptor Ligands
Clarissa G Borba Herkenhoff1, Ericka B Trarbach2, Rafael Loch Batista1,3
1Neuroendocrine Unit, Division of Endocrinology and Metabolism, Clinics Hospital, University of São Paulo Medical School, São Paulo, CEP 05403-010, Brazil.
Context:
Invasive and somatostatin receptor ligand (SRL)-resistant pituitary tumors represent a challenge in the clinical practice of endocrinologists. Efforts have been made to elucidate reliable makers for both. Survivin and eukaryotic translation initiation factor-binding protein 1 (4EBP1) are upregulated in several cancers and involved in apoptosis and cell proliferation.
Objective:
We explored the role of these markers in somatotropinomas.
Methods:
Immunostains for survivin and 4EBP1, and also for somatostatin receptor type 2 (SSTR2), Ki-67, and cytokeratin 18, were analyzed in tissue microarrays containing 52 somatotropinoma samples. Tumor invasiveness was evaluated in all samples while drug resistance was evaluated in 34 patients who received SRL treatment. All these parameters were correlated with first-generation SRL (fg-SRL) responsiveness and tumor invasiveness.
Results:
Low survivin expression (P = 0.04), hyperintense signal on T2 weighted image (T2WI) (P = 0.01), younger age (P = 0.01), sparsely granular adenomas (SGA) (P = 0.04), high postoperative growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels (P = 0.049 and P < 0.001, respectively), and large postoperative tumor size (P = 0.02) were associated with resistance to fg-SRL. Low survivin and SSTR2 expression and high 4EBP1 expression were associated with SGA (P = 0.04, P = 0.01, and P = 0.001, respectively). Younger age (P = 0.03), large tumor pre- and postoperative (P = 0.04 and P = 0.006, respectively), low SSTR2 expression (P = 0.03), and high baseline GH and IGF-1 (P = 0.01 and P = 0.02, respectively) were associated with tumor invasiveness. However, survivin, 4EBP1, Ki-67, and granulation patterns were not associated with tumor invasion.
Conclusion:
This study suggests that low survivin expression is predictive of resistance to fg-SRL in somatotropinomas, but not of tumor invasiveness.
Insights
Low survivin expression predicts resistance to somatostatin receptor ligand (SRL) treatment in pituitary tumors called somatotropinomas. This marker was not associated with tumor invasiveness.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Pituitary tumors, specifically somatotropinomas, can be invasive and resistant to somatostatin receptor ligand (SRL) treatment, posing clinical challenges.
- Survivin and eukaryotic translation initiation factor-binding protein 1 (4EBP1) are proteins implicated in cancer cell apoptosis and proliferation, making them potential markers for tumor behavior.
Purpose of the Study:
- To investigate the role of survivin and 4EBP1 as potential markers for SRL resistance and invasiveness in somatotropinomas.
Main Methods:
- Immunohistochemical analysis of survivin, 4EBP1, SSTR2, Ki-67, and cytokeratin 18 in 52 somatotropinoma samples.
- Evaluation of tumor invasiveness and correlation with SRL treatment response in 34 patients.
Main Results:
- Low survivin expression, along with other factors like T2WI signal and high postoperative GH/IGF-1, was associated with resistance to first-generation SRL (fg-SRL).
- Low survivin and SSTR2 expression, and high 4EBP1 expression were linked to sparsely granular adenomas (SGA).
- Tumor invasiveness correlated with younger age, larger tumor size, low SSTR2, and high baseline GH/IGF-1, but not with survivin, 4EBP1, Ki-67, or granulation patterns.
Conclusions:
- Low survivin expression serves as a predictive marker for resistance to fg-SRL in somatotropinomas.
- Survivin expression is not a reliable indicator of tumor invasiveness in somatotropinomas.
