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The role of hormonal status, morphological subtypes and proliferative marker Ki-67 labeling index on long-term outcomes in patients with acromegaly: a single tertiary center’s experience

Year 2023, , 383 - 388, 27.10.2023
https://doi.org/10.38053/acmj.1343934

Abstract

Aims: Acromegaly is a rare disorder resulting from benign growth hormone secreting pituitary adenomas. Many factors affect long-term outcomes in acromegaly. In this study we aimed to investigate effects of hormonal status, morphological subtypes, immunohistochemical expression of pituitary hormones and Ki-67 labeling index on long-term outcomes in patients with acromegaly.
Methods:. We collected the medical and pathological records of sixty-four patients who underwent surgery for growth hormone (GH) secreting somatotroph tumors between 2005-2017.
Results: The remission rate after surgery was 48% (31/64) in all patients (33% for macroadenomas, 94% for microadenomas; p <0.001) with a median follow up of 48 months (12-198). There was no significant relationship between Ki-67 labeling index and remission status (p=0.140). The remission group were significantly older than the nonremission group [47 (21-67) vs 36 (18-56); p=0.012]. We found a statistically significant positive correlation between insulin-like growth factor 1 (IGF-1) levels and Ki-67 labeling index (r=+0.382, p=0.004). Also, there was a significant positive correlation between tumor size and GH (r=+0.368, p=0.027). There was no difference between densely and sparsely granulated adenomas in terms of surgical remission (p=0.866). In multivariate regression analysis, tumor size ≥ 10 mm (macroadenoma) was significant independent variable in predicting remission [95% CI [16.95 (1.92-142)]; p=0.011]. The baseline cortisol levels was correlated negatively with the Ki-67 labeling index (r=+0.293, p=0.02).
Conclusion: The Ki-67 labeling index was not associated with surgical remission in patients with acromegaly. However, the Ki-67 labeling index was higher in younger patients and those with larger adenomas.

References

  • Hazer DB, Işık S, Berker D, et al. Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria. J Neurosurg. 2013;119(6):1467-1477.
  • Nomikos P, Buchfelder M, Fahlbusch R. The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical ‘cure’. Eur J Endocrinol. 2005;152(3):379-387.
  • Katznelson L, Laws ER, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951.
  • Rieger A, Rainov NG, Ebel H, et al. Factors predicting pituitary adenoma invasiveness in acromegalic patients. Neurosurg Rev. 1997;20(3):182-187.
  • Fusco A, Zatelli MC, Bianchi A, et al. Prognostic significance of the Ki-67 labeling index in growth hormone-secreting pituitary adenomas. J Clin Endocrinol Metab. 2008;93(7):2746-2750.
  • Alimohamadi M, Ownagh V, Mahouzi L, Ostovar A, Abbassioun K, Amirjmshidi A. The impact of immunohistochemical markers of Ki-67 and p53 on the long-term outcome of growth hormone-secreting pituitary adenomas: a cohort study. Asian J Neurosurg. 2014;9(3):130-136.
  • Thapar K, Kovacs K, Scheithauer BW, et al. Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery. 1996;38(1):99-106; discussion -7.
  • Filippella M, Galland F, Kujas M, et al. Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas: a clinical and immunohistochemical study. Clin Endocrinol (Oxf). 2006;65(4):536-543.
  • Salehi F, Agur A, Scheithauer BW, Kovacs K, Lloyd RV, Cusimano M. Ki-67 in pituitary neoplasms: a review--part I. Neurosurgery. 2009;65(3):429-437; discussion 37.
  • Knosp E, Kitz K, Perneczky A. Proliferation activity in pituitary adenomas: measurement by monoclonal antibody Ki-67. Neurosurgery. 1989;25(6):927-930.
  • Giustina A, Chanson P, Bronstein MD, et al. A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab. 2010;95(7):3141-148.
  • Melmed S, Braunstein GD, Horvath E, Ezrin C, Kovacs K. Pathophysiology of acromegaly. Endocr Rev. 1983;4(3):271-290.
  • Wang YY, Waqar M, Abou-Zeid A, et al. Value of early post-operative growth hormone testing in predicting long-term remission and residual disease after transsphenoidal surgery for acromegaly. Neuroendocrinology. 2022;112(4):345-357.
  • Antunes X, Ventura N, Camilo GB, et al. Predictors of surgical outcome and early criteria of remission in acromegaly. Endocrine. 2018;60(3):415-422.
  • Babu H, Ortega A, Nuno M, et al. Long-term endocrine outcomes following endoscopic endonasal transsphenoidal surgery for acromegaly and associated prognostic factors. Neurosurgery. 2017;81(2):357-366.
  • Jaffrain-Rea ML, Di Stefano D, Minniti G, et al. A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas. Endocr Relat Cancer. 2002;9(2):103-113.
  • Mohseni S, Aboeerad M, Sharifi F, Tavangar SM, Mohajeri-Tehrani M. Associations of Ki-67 labeling index with clinical and paraclinical features of growth hormone-secreting pituitary adenomas: a single center report from Iran. Int J Endocrinol Metab. 2019;17(2):e81983.
  • Pinto EM, Bronstein MD. [Molecular aspects of pituitary tumorigenesis]. Arq Bras Endocrinol Metabol. 2008;52(4):599-610.
  • Mastronardi L, Guiducci A, Puzzilli F. Lack of correlation between Ki-67 labelling index and tumor size of anterior pituitary adenomas. BMC Cancer. 2001;1:12.
  • Mazal PR, Czech T, Sedivy R, et al. Prognostic relevance of intracytoplasmic cytokeratin pattern, hormone expression profile, and cell proliferation in pituitary adenomas of akromegalic patients. Clin Neuropathol. 2001;20(4):163-171.
  • Yamada S, Aiba T, Sano T, et al. Growth hormone-producing pituitary adenomas: correlations between clinical characteristics and morphology. Neurosurgery. 1993;33(1):20-27.
  • Obari A, Sano T, Ohyama K, et al. Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form. Endocr Pathol. 2008;19(2):82-91.
  • Brzana J, Yedinak CG, Gultekin SH, Delashaw JB, Fleseriu M. Growth hormone granulation pattern and somatostatin receptor subtype 2A correlate with postoperative somatostatin receptor ligand response in acromegaly: a large single center experience. Pituitary. 2013;16(4):490-498.
  • Swanson AA, Erickson D, Donegan DM, et al. Clinical, biological, radiological, and pathological comparison of sparsely and densely granulated somatotroph adenomas: a single center experience from a cohort of 131 patients with acromegaly. Pituitary. 2021;24(2):192-206.
  • Shahrestani S, Cardinal T, Micko A, et al. Neural network modeling for prediction of recurrence, progression, and hormonal non-remission in patients following resection of functional pituitary adenomas. Pituitary. 2021;24(4):523-529.
  • Sakayama K, Mashima N, Kidani T, Miyazaki T, Yamamoto H, Masuno H. Effect of cortisol on cell proliferation and the expression of lipoprotein lipase and vascular endothelial growth factor in a human osteosarcoma cell line. Cancer Chemother Pharmacol. 2008;61(3):471-479.
  • Dong J, Li J, Cui L, et al. The proliferative effect of cortisol on bovine endometrial epithelial cells. Reprod Biol Endocrinol. 2019;17(1):97.
  • Fernandez-Rodriguez E, Casanueva FF, Bernabeu I. Update on prognostic factors in acromegaly: is a risk score possible? Pituitary. 2015;18(3):431-440.
  • Yildirim AE, Sahinoglu M, Divanlioglu D, et al. Endoscopic endonasal transsphenoidal treatment for acromegaly: 2010 consensus criteria for remission and predictors of outcomes. Turk Neurosurg. 2014;24(6):906-912.
  • Shirvani M, Motiei-Langroudi R. Transsphenoidal surgery for growth hormone-secreting pituitary adenomas in 130 patients. World Neurosurg. 2014;81(1):125-130.
Year 2023, , 383 - 388, 27.10.2023
https://doi.org/10.38053/acmj.1343934

Abstract

References

  • Hazer DB, Işık S, Berker D, et al. Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria. J Neurosurg. 2013;119(6):1467-1477.
  • Nomikos P, Buchfelder M, Fahlbusch R. The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical ‘cure’. Eur J Endocrinol. 2005;152(3):379-387.
  • Katznelson L, Laws ER, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951.
  • Rieger A, Rainov NG, Ebel H, et al. Factors predicting pituitary adenoma invasiveness in acromegalic patients. Neurosurg Rev. 1997;20(3):182-187.
  • Fusco A, Zatelli MC, Bianchi A, et al. Prognostic significance of the Ki-67 labeling index in growth hormone-secreting pituitary adenomas. J Clin Endocrinol Metab. 2008;93(7):2746-2750.
  • Alimohamadi M, Ownagh V, Mahouzi L, Ostovar A, Abbassioun K, Amirjmshidi A. The impact of immunohistochemical markers of Ki-67 and p53 on the long-term outcome of growth hormone-secreting pituitary adenomas: a cohort study. Asian J Neurosurg. 2014;9(3):130-136.
  • Thapar K, Kovacs K, Scheithauer BW, et al. Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery. 1996;38(1):99-106; discussion -7.
  • Filippella M, Galland F, Kujas M, et al. Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas: a clinical and immunohistochemical study. Clin Endocrinol (Oxf). 2006;65(4):536-543.
  • Salehi F, Agur A, Scheithauer BW, Kovacs K, Lloyd RV, Cusimano M. Ki-67 in pituitary neoplasms: a review--part I. Neurosurgery. 2009;65(3):429-437; discussion 37.
  • Knosp E, Kitz K, Perneczky A. Proliferation activity in pituitary adenomas: measurement by monoclonal antibody Ki-67. Neurosurgery. 1989;25(6):927-930.
  • Giustina A, Chanson P, Bronstein MD, et al. A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab. 2010;95(7):3141-148.
  • Melmed S, Braunstein GD, Horvath E, Ezrin C, Kovacs K. Pathophysiology of acromegaly. Endocr Rev. 1983;4(3):271-290.
  • Wang YY, Waqar M, Abou-Zeid A, et al. Value of early post-operative growth hormone testing in predicting long-term remission and residual disease after transsphenoidal surgery for acromegaly. Neuroendocrinology. 2022;112(4):345-357.
  • Antunes X, Ventura N, Camilo GB, et al. Predictors of surgical outcome and early criteria of remission in acromegaly. Endocrine. 2018;60(3):415-422.
  • Babu H, Ortega A, Nuno M, et al. Long-term endocrine outcomes following endoscopic endonasal transsphenoidal surgery for acromegaly and associated prognostic factors. Neurosurgery. 2017;81(2):357-366.
  • Jaffrain-Rea ML, Di Stefano D, Minniti G, et al. A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas. Endocr Relat Cancer. 2002;9(2):103-113.
  • Mohseni S, Aboeerad M, Sharifi F, Tavangar SM, Mohajeri-Tehrani M. Associations of Ki-67 labeling index with clinical and paraclinical features of growth hormone-secreting pituitary adenomas: a single center report from Iran. Int J Endocrinol Metab. 2019;17(2):e81983.
  • Pinto EM, Bronstein MD. [Molecular aspects of pituitary tumorigenesis]. Arq Bras Endocrinol Metabol. 2008;52(4):599-610.
  • Mastronardi L, Guiducci A, Puzzilli F. Lack of correlation between Ki-67 labelling index and tumor size of anterior pituitary adenomas. BMC Cancer. 2001;1:12.
  • Mazal PR, Czech T, Sedivy R, et al. Prognostic relevance of intracytoplasmic cytokeratin pattern, hormone expression profile, and cell proliferation in pituitary adenomas of akromegalic patients. Clin Neuropathol. 2001;20(4):163-171.
  • Yamada S, Aiba T, Sano T, et al. Growth hormone-producing pituitary adenomas: correlations between clinical characteristics and morphology. Neurosurgery. 1993;33(1):20-27.
  • Obari A, Sano T, Ohyama K, et al. Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form. Endocr Pathol. 2008;19(2):82-91.
  • Brzana J, Yedinak CG, Gultekin SH, Delashaw JB, Fleseriu M. Growth hormone granulation pattern and somatostatin receptor subtype 2A correlate with postoperative somatostatin receptor ligand response in acromegaly: a large single center experience. Pituitary. 2013;16(4):490-498.
  • Swanson AA, Erickson D, Donegan DM, et al. Clinical, biological, radiological, and pathological comparison of sparsely and densely granulated somatotroph adenomas: a single center experience from a cohort of 131 patients with acromegaly. Pituitary. 2021;24(2):192-206.
  • Shahrestani S, Cardinal T, Micko A, et al. Neural network modeling for prediction of recurrence, progression, and hormonal non-remission in patients following resection of functional pituitary adenomas. Pituitary. 2021;24(4):523-529.
  • Sakayama K, Mashima N, Kidani T, Miyazaki T, Yamamoto H, Masuno H. Effect of cortisol on cell proliferation and the expression of lipoprotein lipase and vascular endothelial growth factor in a human osteosarcoma cell line. Cancer Chemother Pharmacol. 2008;61(3):471-479.
  • Dong J, Li J, Cui L, et al. The proliferative effect of cortisol on bovine endometrial epithelial cells. Reprod Biol Endocrinol. 2019;17(1):97.
  • Fernandez-Rodriguez E, Casanueva FF, Bernabeu I. Update on prognostic factors in acromegaly: is a risk score possible? Pituitary. 2015;18(3):431-440.
  • Yildirim AE, Sahinoglu M, Divanlioglu D, et al. Endoscopic endonasal transsphenoidal treatment for acromegaly: 2010 consensus criteria for remission and predictors of outcomes. Turk Neurosurg. 2014;24(6):906-912.
  • Shirvani M, Motiei-Langroudi R. Transsphenoidal surgery for growth hormone-secreting pituitary adenomas in 130 patients. World Neurosurg. 2014;81(1):125-130.
There are 30 citations in total.

Details

Primary Language English
Subjects Endocrinology
Journal Section Research Articles
Authors

Çağlar Keskin 0000-0001-5503-4468

Mustafa Şahin 0000-0002-4718-0083

Saba Kiremitçi 0000-0001-8868-1362

Esra Erden This is me 0000-0002-4174-8897

Asena Gökçay Canpolat 0000-0003-1186-2960

Şule Canlar 0000-0001-7695-9611

Murat Cinel 0000-0001-9241-7900

Özge Baş Aksu 0000-0003-3124-9477

Özgür Demir 0000-0001-6555-3579

Rıfat Emral 0000-0002-5732-2284

Sevim Güllü 0000-0002-8027-8891

Demet Çorapçıoğlu 0000-0003-0940-9147

Early Pub Date October 26, 2023
Publication Date October 27, 2023
Published in Issue Year 2023

Cite

AMA Keskin Ç, Şahin M, Kiremitçi S, Erden E, Gökçay Canpolat A, Canlar Ş, Cinel M, Baş Aksu Ö, Demir Ö, Emral R, Güllü S, Çorapçıoğlu D. The role of hormonal status, morphological subtypes and proliferative marker Ki-67 labeling index on long-term outcomes in patients with acromegaly: a single tertiary center’s experience. Anatolian Curr Med J / ACMJ / acmj. October 2023;5(4):383-388. doi:10.38053/acmj.1343934

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