{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:26:11Z","timestamp":1786955171531,"version":"build-2736575974"},"reference-count":27,"publisher":"AOSIS","issue":"1","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Background:\u00a0In Nigeria, patients with pituitary neuroendocrine tumours (PitNETs) commonly present late with complications. Early identification of aggressive PitNETs could improve outcomes.\nObjective:\u00a0This study aimed to determine frequency and degree of cyclin D1 expression in PitNETs and compare levels in aggressive versus non-aggressive tumours and normal pituitary.\nMethods:\u00a0Retrospective case\u2013control study (2010\u20132019) using two tissue microarrays from mitotically active hotspots on paraffin blocks: 70 histologically diagnosed PitNETs and 29 normal pituitary controls. Immunohistochemistry was performed for Ki-67, cyclin D1, anterior pituitary transcription factors, CK MNF116, and hormones. Aggressive PitNETs were classified per 2022 WHO criteria (mitotic rate &gt; 2\/10 HPF, Ki-67 \u2265 3% or radiological invasion).\nResults:\u00a0Fourteen (20%) PitNETs were classified as aggressive (8 invasive, 6 proliferative). Median age in the aggressive group was 36.5 years with equal gender distribution. The commonest aggressive subtype was PIT-1 lineage lactotroph PitNET (5\/14, 35.7%). Moderate\u2013strong nuclear cyclin D1 expression (IRS \u2265 5) occurred in 85.7% of aggressive PitNETs versus 67.9% of non-aggressive tumours and 0% of controls (p\u00a0&lt; 0.01). Positive predictive value of cyclin D1 for aggressiveness among PitNETs was 24% (12\/50 positive cases).\nConclusion:\u00a0Cyclin D1 is significantly overexpressed in aggressive PitNETs compared with non-aggressive tumours and normal pituitary, suggesting its potential as a biomarker for early detection, risk stratification, and therapeutic targeting, especially in resource-limited settings.\nWhat the study adds:\u00a0This study demonstrates marked cyclin D1 overexpression in aggressive PitNETs, supporting its use as a biomarker for early detection, more precise risk stratification, and as a potential therapeutic target in resource-limited environments.<\/jats:p>","DOI":"10.4102\/ajlm.v15i1.3077","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:08:38Z","timestamp":1786954118000},"update-policy":"https:\/\/doi.org\/10.4102\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential expression of cyclin D1 in pituitary neuroendocrine tumours: Relation to aggressive potential"],"prefix":"10.4102","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0427-7424","authenticated-orcid":false,"given":"Kasiemobi E.","family":"Uchime","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00gkd5869","id-type":"ROR","asserted-by":"publisher"}],"name":"Lagos University Teaching Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5251-9689","authenticated-orcid":false,"given":"Nicholas A.","family":"Awolola","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00gkd5869","id-type":"ROR","asserted-by":"publisher"}],"name":"Lagos University Teaching Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1623-5536","authenticated-orcid":false,"given":"Charles C.","family":"Anunobi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00gkd5869","id-type":"ROR","asserted-by":"publisher"}],"name":"Lagos University Teaching Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5316-1831","authenticated-orcid":false,"given":"Olufemi B.","family":"Bankole","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00gkd5869","id-type":"ROR","asserted-by":"publisher"}],"name":"Lagos University Teaching Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8235-3461","authenticated-orcid":false,"given":"Adekunbiola A.","family":"Banjo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00gkd5869","id-type":"ROR","asserted-by":"publisher"}],"name":"Lagos University Teaching Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8681-1597","authenticated-orcid":false,"given":"Sung-Hye","family":"Park","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01z4nnt86","id-type":"ROR","asserted-by":"publisher"}],"name":"Seoul National University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2580","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"Asa SL, Mete O, Perry A, Osamura RY. Overview of the 2022 WHO Classification of Pituitary Tumors. Endocr Pathol. 2022;33(1):6\u201326. https:\/\/doi.org\/10.1007\/s12022-022-09703-7","DOI":"10.1007\/s12022-022-09703-7"},{"key":"ref1","doi-asserted-by":"crossref","unstructured":"De Robles P, Fiest KM, Frolkis AD, et al. The worldwide incidence and prevalence of primary brain tumors: A systematic review and meta-analysis. Neuro Oncol. 2015;17(6):776\u2013783. https:\/\/doi.org\/10.1093\/neuonc\/nou283","DOI":"10.1093\/neuonc\/nou283"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Ohaegbulam SC, Saddeqi N, Ikerionwu S. Intracranial tumours in Enugu, Nigeria. Cancer. 1980;46(10):2322\u20132324. https:\/\/doi.org\/10.1002\/1097-0142(19801115)46:10<2322::AID-CNCR2820461034>3.0.CO;2-F","DOI":"10.1002\/1097-0142(19801115)46:10<2322::AID-CNCR2820461034>3.0.CO;2-F"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Igun GO. Diagnosis and management of brain tumours at Jos University Teaching Hospital, Nigeria. East Afr Med J. 2001;78(3):148\u2013151. https:\/\/doi.org\/10.4314\/eamj.v78i3.9082","DOI":"10.4314\/eamj.v78i3.9082"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Jibrin P, Ibebuike K, Ado-wanka AN. Histo-pathological pattern of intracranial tumours in National Hospital, Abuja. Afr Health Sci. 2018;18(2):281\u2013286. https:\/\/doi.org\/10.4314\/ahs.v18i2.12","DOI":"10.4314\/ahs.v18i2.12"},{"key":"ref5","unstructured":"Lloyd RV, Osamura RY, Kl\u00f6ppel G, Rosai J, editor. WHO classification of tumours of endocrine organs. 4th ed. Lyon: IARC Press; 2017."},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Casar-Borota O, Burman P, Lopes MB. The 2022 WHO classification of tumors of the pituitary gland: An update on aggressive and metastatic pituitary neuroendocrine tumors. Brain Pathol. 2025;35(1):e13302. https:\/\/doi.org\/10.1111\/bpa.13302","DOI":"10.1111\/bpa.13302"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Villa C, Vasiljevic A, Jaffrain-Rea ML, et al. A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): A European Pituitary Pathology Group (EPPG) proposal. Virchows Archiv. 2019;475(6):687\u2013692. https:\/\/doi.org\/10.1007\/s00428-019-02655-0","DOI":"10.1007\/s00428-019-02655-0"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Trouillas J, Jaffrain-Rea ML, Vasiljevic A, et al. How to classify pituitary neuroendocrine tumors (PitNET)s according to the 2022 WHO classification. Cancers (Basel). 2023;15(4):1123. https:\/\/doi.org\/10.3390\/cancers15041123","DOI":"10.3390\/cancers15041123"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Trouillas J, Roy P, Sturm N, Dantony E, Cortet-Rudelli C, Viennet G, et al. A new prognostic clinicopathological classification of pitutiary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up. Acta Neuropathol. 2013;126(1):123\u2013135. https:\/\/doi.org\/10.1007\/s00401-013-1084-y","DOI":"10.1007\/s00401-013-1084-y"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Hewedi IH, Osman WM, El Mahdy MM. Differential expression of cyclin D1 in human pituitary tumors: relation to MIB-1 and p27\/Kip1 labeling indices. J Egypt Natl Canc Inst. 2011;23(4):171\u2013179. https:\/\/doi.org\/10.1016\/j.jnci.2011.11.003","DOI":"10.1016\/j.jnci.2011.11.003"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Sherr CJ, Beach D, Shapiro GI. Targeting CDK4 and CDK6: From Discovery to Therapy. Cancer Discov. 2016;6(4):353\u2013367. https:\/\/doi.org\/10.1158\/2159-8290.CD-15-0894","DOI":"10.1158\/2159-8290.CD-15-0894"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Anderson E, Heller RS, Lechan RM, Heilman CB. Regression of a nonfunctioning pituitary macroadenoma on the CDK4\/6 inhibitor palbociclib: Case report. Neurosurg Focus. 2018;44(6):E9. https:\/\/doi.org\/10.3171\/2018.2.FOCUS17660","DOI":"10.3171\/2018.2.FOCUS17660"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Knosp E, Kitz K, Steiner E, Matula C. Pituitary adenomas with parasellar invasion. Acta Neurochir Suppl (Wien). 1991;53:65\u201371. https:\/\/doi.org\/10.1007\/978-3-7091-9183-5_12","DOI":"10.1007\/978-3-7091-9183-5_12"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Hardy J. Transsphenoidal microsurgery of the normal and pathological pituitary. Clin Neurosurg. 1969;16:185\u2013217. https:\/\/doi.org\/10.1093\/neurosurgery\/16.CN_suppl_1.185","DOI":"10.1093\/neurosurgery\/16.CN_suppl_1.185"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Salami A, Ajani M, Adeolu A, et al. Proliferation index in pituitary adenomas from a black African population. Alexandria J Med. 2017;53(3):281\u2013284. https:\/\/doi.org\/10.1016\/j.ajme.2016.11.003","DOI":"10.1016\/j.ajme.2016.11.003"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Grimm F, Maurus R, Beschorner R, et al. Ki-67 labeling index and expression of p53 are non-predictive for invasiveness and tumor size in functional and nonfunctional pituitary adenomas. Acta Neurochir (Wien). 2019;161(6):1149\u20131156. https:\/\/doi.org\/10.1007\/s00701-019-03879-4.","DOI":"10.1007\/s00701-019-03879-4"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Hasanov R, Aydo\u011fan B\u0130, Kiremit\u00e7i S, Erden E, G\u00fcll\u00fc S. The prognostic roles of the Ki-67 proliferation index, p53 expression, mitotic index, and radiological tumor invasion in pituitary adenomas. Endocr Pathol. 2019;30(1):49\u201355. https:\/\/doi.org\/10.1007\/s12022-018-9563-2.","DOI":"10.1007\/s12022-018-9563-2"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Cottier JP, Destrieux C, Brunereau L, et al. Cavernous sinus invasion by pituitary adenoma: MR imaging. Radiology. 2000;215(2):463\u2013469. https:\/\/doi.org\/10.1148\/radiology.215.2.r00ap18463","DOI":"10.1148\/radiology.215.2.r00ap18463"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Selman WR, Laws ER Jr, Scheithauer BW, Carpenter SM, Laws ER Sr. The occurrence of dural invasion in pituitary adenomas. J Neurosurg. 1986;64(3):402\u2013407. https:\/\/doi.org\/10.3171\/jns.1986.64.3.0402","DOI":"10.3171\/jns.1986.64.3.0402"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Meij BP, Lopes MB, Ellegala DB, Alden TD, Laws ER Jr. The long-term significance of microscopic dural invasion in 354 patients with pituitary adenomas treated with transsphenoidal surgery. J Neurosurg. 2002;96(2):195\u2013208. https:\/\/doi.org\/10.3171\/jns.2002.96.2.0195","DOI":"10.3171\/jns.2002.96.2.0195"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Amar AP, Hinton DR, Krieger MD, Weiss MH. Invasive pituitary adenomas: significance of proliferation parameters. Pituitary. 1999;2(2):117\u2013122. https:\/\/doi.org\/10.1023\/A:1009931413106","DOI":"10.1023\/A:1009931413106"},{"key":"ref22","unstructured":"Liu C, Xie W, Wu D, Li Z, Li C, Zhang Y. Expression of cell-cycle regulators is associated with invasive behavior and poor prognosis in prolactinomas. Int J Clin Exp Pathol [serial online]. 2016 [cited n.d.];9(3):3245\u20133255. Available from: https:\/\/www.ijcep.com\/files\/ijcep0021009.pdf"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Xu L, Khaddour K, Chen J, Rich KM, Perrin RJ, Campian JL. Pituitary carcinoma: Two case reports and review of literature. World J Clin Oncol. 2020;11(2):91\u2013102 https:\/\/doi.org\/10.5306\/wjco.v11.i2.91","DOI":"10.5306\/wjco.v11.i2.91"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Jordan S, Lidhar K, Korbonits M, Lowe DG, Grossman AB. Cyclin D and cyclin E expression in normal and adenomatous pituitary. Eur J Endocrinol. 2000;143(5):R1\u2013R6. https:\/\/doi.org\/10.1530\/eje.0.143r001","DOI":"10.1530\/eje.0.143r001"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Turner JJ, Leen SL, Ostor AG, McNicol AM, Cummings MK. Cyclin D1 expression distinguishes pituitary adenomas from normal pituitary. J Clin Pathol. 2005;58(11):1174\u20131178. https:\/\/doi.org\/10.1136\/jcp.2005.027508","DOI":"10.1136\/jcp.2005.027508"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Hewedi IH, Farahat N, Jelassaty S, El-Zaytouny M, El-Moneim NA. Cyclin D1 and MIB-1 in pituitary adenomas: Correlation with cell proliferation and aggressiveness. Pathol Res Pract. 2012;208(2):68\u201374. https:\/\/doi.org\/10.1016\/j.prp.2011.11.007","DOI":"10.1016\/j.prp.2011.11.007"}],"container-title":["African Journal of Laboratory Medicine"],"original-title":[],"link":[{"URL":"https:\/\/ajlmonline.org\/index.php\/ajlm\/article\/view\/3077\/3629","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:09:17Z","timestamp":1786954157000},"score":1,"resource":{"primary":{"URL":"https:\/\/ajlmonline.org\/index.php\/ajlm\/article\/view\/3077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,24]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.4102\/ajlm.v15i1.3077","relation":{},"ISSN":["2225-2002","2225-2010"],"issn-type":[{"value":"2225-2002","type":"print"},{"value":"2225-2010","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,24]]},"article-number":"a3077"}}