Survivin: A Potential Marker of Resistance to Somatostatin Receptor Ligands

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Borba Herkenhoff, Clarissa G. ; Trarbach, Ericka B. ; Batista, Rafael Loch ; Soares, Ibere Cauduro ; Frassetto, Fernando Pereira ; Pereira do Nascimento, Felipe Barjud ; Pajaro Grande, Isabella Pacetti ; Silva, Paula P. B. ; Duarte, Felipe H. G. ; Bronstein, Marcello D. ; Jallad, Raquel S.

• Document type: Journal article
• Source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. N/A, p. 12-pg., 2022-10-24.

Abstract

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. (AU)

• FAPESP's process: 16/23765-0 - Acromegaly: mineral density, microarquitecture and bone strength before and after treatment with biphosphonate NEW TITLE: Bone microarchitecture and strength evaluation in adults with diagnosis of acromegaly
• Grantee: Raquel Soares Jallad
• Support Opportunities: Regular Research Grants