Evaluation of the Potential of the Ki67 Index to Predict Tumor Evolution in Patients with Pituitary Adenoma

Overview

Journal Int J Clin Exp Pathol

Specialty Pathology

Date 2020 Jan 15

PMID 31933748

Citations 10

Authors

Carolina Petry

Jefferson Henrique Zwir Poli

Isabella de Azevedo Dossin

Carolina Garcia Soares Leaes Rech

Julia Fernanda Semmelmann Pereira Lima

Nelson Pires Ferreira

Miriam da Costa Oliveira

Affiliations

Soon will be listed here.

Abstract

The aggressive course of a number of pituitary adenomas requires the investigation of potential predictors. This study aimed to investigate the proliferation marker Ki67 as a predictor of postoperative outcome in patients with pituitary adenoma regarding recurrence and regrowth of the tumor, using a Ki67 cut-off value of 3%. This retrospective study included 52 patients with pituitary adenoma who had undergone adenomectomy and had a pituitary image taken at least 1 year after surgery. Patients were divided according to Ki67 expression into high (≥3%) vs. low (<3%) levels of Ki67. The two groups were similar regarding the preoperative tumor invasion grade. The Ki67 index ranged from 0 to 30%; in 23 cases, Ki67 was ≥3%. The two groups were similar regarding tumor recurrence and regrowth: 4 cases (28%) of recurrence in the Ki67<3% group vs. none in the Ki67≥3% group (P=0.26); and 2 cases (13%) of regrowth in the Ki67<3% group vs. 7 cases (43%) in the Ki67≥3% group (P=0.11). A subgroup analysis was performed for nonfunctioning adenomas. Recurrence rates remained similar between groups (Ki67<3% group: 1 case [20%]; Ki67≥3% group: none; P>0.99), whereas regrowth rates were higher in the Ki67≥3% group (6 cases [67%] vs. 2 cases [17%] in the Ki67<3% group; P=0.03). The patient with the highest Ki67 index (30%) developed pituitary carcinoma. The results allow us to suggest the adoption of a stricter control of image monitoring in nonfunctioning adenomas with incomplete resection associated with a Ki67 index ≥3%.

Citing Articles

Spontaneous Cerebrospinal Fluid Rhinorrhea in Pre-operative Pituitary Adenoma: A Report of Two Cases.

Eisold J, Dimante D, Pollock J, Shoakazemi A, Stojanovic N Cureus. 2024; 16(10):e71642.

PMID: 39553112 PMC: 11566357. DOI: 10.7759/cureus.71642.

Risk factor analysis and prediction model to establish recurrence or progression of non-functioning pituitary adenomas in men after transnasal sphenoidal surgery.

Zhong J, Chen Y, Wang M, Li J, Li Z, Li H Sci Rep. 2024; 14(1):21607.

PMID: 39284867 PMC: 11405691. DOI: 10.1038/s41598-024-72944-5.

Pituitary Adenoma: rs2236750, rs34037914, and rs267606574 Genetic Variants, Serum Levels, and Ki-67 Labeling Index Associations.

Gedvilaite-Vaicechauskiene G, Kriauciuniene L, Tamasauskas A, Rovite V, Mandrika I, Wu S Medicina (Kaunas). 2024; 60(8).

PMID: 39202532 PMC: 11356775. DOI: 10.3390/medicina60081252.

[Quantification of Ki-67 in PitNET (pituitary neuroendocrine tumors)/adenomas].

Klein J, Saeger K, Saeger W Pathologie (Heidelb). 2024; 45(5):339-343.

PMID: 38992316 PMC: 11343892. DOI: 10.1007/s00292-024-01319-4.

Clinicopathological analysis of non-functioning pituitary adenomas (PAs) according to the 2022 WHO classification.

Kim Y, Ahn S, Lee Y, Jeun S, Park J Pituitary. 2024; 27(5):665-672.

PMID: 38896347 DOI: 10.1007/s11102-024-01414-y.

References

Zhao D, Tomono Y, Nose T . Expression of P27kip1 and Ki-67 in pituitary adenomas: an investigation of marker of adenoma invasiveness. Acta Neurochir (Wien). 1999; 141(2):187-92. DOI: 10.1007/s007010050285. View

Gruppetta M, Formosa R, Falzon S, Ariff Scicluna S, Falzon E, Degeatano J . Expression of cell cycle regulators and biomarkers of proliferation and regrowth in human pituitary adenomas. Pituitary. 2017; 20(3):358-371. DOI: 10.1007/s11102-017-0803-0. View

Madsen H, Borges T, Knox A, Michaelis K, Xu M, Lillehei K . Giant pituitary adenomas: pathologic-radiographic correlations and lack of role for p53 and MIB-1 labeling. Am J Surg Pathol. 2011; 35(8):1204-13. DOI: 10.1097/PAS.0b013e31821e8c96. View

Pizarro C, Oliveira M, Coutinho L, Ferreira N . Measurement of Ki-67 antigen in 159 pituitary adenomas using the MIB-1 monoclonal antibody. Braz J Med Biol Res. 2004; 37(2):235-43. DOI: 10.1590/s0100-879x2004000200011. View

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. 2015; 9(3):130-6. PMC: 4323896. DOI: 10.4103/1793-5482.142732. View

Righi A, Agati P, Sisto A, Frank G, Faustini-Fustini M, Agati R . A classification tree approach for pituitary adenomas. Hum Pathol. 2012; 43(10):1627-37. DOI: 10.1016/j.humpath.2011.12.003. View

Tortosa F, Webb S . Atypical pituitary adenomas: 10 years of experience in a reference centre in Portugal. Neurologia. 2015; 31(2):97-105. DOI: 10.1016/j.nrl.2015.06.010. View

Ekramullah S, Saitoh Y, Arita N, Ohnishi T, Hayakawa T . The correlation of Ki-67 staining indices with tumour doubling times in regrowing non-functioning pituitary adenomas. Acta Neurochir (Wien). 1996; 138(12):1449-55. DOI: 10.1007/BF01411125. View

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. PMC: 56633. DOI: 10.1186/1471-2407-1-12. View

10.

Pan L, Chen Z, Liu Y, Zhao J . Magnetic resonance imaging and biological markers in pituitary adenomas with invasion of the cavernous sinus space. J Neurooncol. 2005; 74(1):71-6. DOI: 10.1007/s11060-004-6150-9. View

11.

Wolfsberger S, Wunderer J, Zachenhofer I, Czech T, Bocher-Schwarz H, Hainfellner J . Expression of cell proliferation markers in pituitary adenomas--correlation and clinical relevance of MIB-1 and anti-topoisomerase-IIalpha. Acta Neurochir (Wien). 2004; 146(8):831-9. DOI: 10.1007/s00701-004-0298-0. View

12.

Yokoyama S, Hirano H, Moroki K, Goto M, Imamura S, Kuratsu J . Are nonfunctioning pituitary adenomas extending into the cavernous sinus aggressive and/or invasive?. Neurosurgery. 2001; 49(4):857-62; discussion 862-3. DOI: 10.1097/00006123-200110000-00014. View

13.

Ramirez C, Cheng S, Vargas G, Asa S, Ezzat S, Gonzalez B . Expression of Ki-67, PTTG1, FGFR4, and SSTR 2, 3, and 5 in nonfunctioning pituitary adenomas: a high throughput TMA, immunohistochemical study. J Clin Endocrinol Metab. 2012; 97(5):1745-51. DOI: 10.1210/jc.2011-3163. View

14.

Trouillas J . In search of a prognostic classification of endocrine pituitary tumors. Endocr Pathol. 2014; 25(2):124-32. DOI: 10.1007/s12022-014-9322-y. View

15.

Chiloiro S, Bianchi A, Doglietto F, de Waure C, Giampietro A, Fusco A . Radically resected pituitary adenomas: prognostic role of Ki 67 labeling index in a monocentric retrospective series and literature review. Pituitary. 2013; 17(3):267-76. DOI: 10.1007/s11102-013-0500-6. View

16.

Mizoue T, Kawamoto H, Arita K, Kurisu K, Tominaga A, Uozumi T . MIB1 immunopositivity is associated with rapid regrowth of pituitary adenomas. Acta Neurochir (Wien). 1997; 139(5):426-31; discussion 431-2. DOI: 10.1007/BF01808879. View

17.

Righi A, Morandi L, Leonardi E, Farnedi A, Marucci G, Sisto A . Galectin-3 expression in pituitary adenomas as a marker of aggressive behavior. Hum Pathol. 2013; 44(11):2400-9. DOI: 10.1016/j.humpath.2013.05.020. View

18.

Ferreira J, de Mello P, Magalhaes A, Botelho C, Naves L, Nose V . [Non-functioning pituitary adenomas: clinical features and immunohistochemistry]. Arq Neuropsiquiatr. 2006; 63(4):1070-8. DOI: 10.1590/s0004-282x2005000600029. View

19.

Filippella M, Galland F, Kujas M, Young J, Faggiano A, Lombardi G . 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):536-43. DOI: 10.1111/j.1365-2265.2006.02630.x. View

20.

Chatzellis E, Alexandraki K, Androulakis I, Kaltsas G . Aggressive pituitary tumors. Neuroendocrinology. 2015; 101(2):87-104. DOI: 10.1159/000371806. View