Journal of Pathology and Translational Medicine

Original Articles

Association of PTTG1 expression with invasiveness of non-functioning pituitary adenomas: Su Jung Kum, Hye Won Lee, Soon Gu Kim, Hyungsik Park, Ilseon Hwang, Sang Pyo Kim; J Pathol Transl Med. 2022;56(1):22-31. Published online October 15, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.31

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Background
Pituitary tumor transforming gene 1 (PTTG1), paired-like homeodomain 2 (PITX2), and galectin-3 have been widely studied as predictive biomarkers for various tumors and are involved in tumorigenesis and tumor progression. We evaluated the usefulness of PTTG1, PITX2, and galectin-3 as predictive biomarkers for invasive non-functioning pituitary adenomas (NFPAs) by determining the relationship between the expressions of these three proteins and the invasiveness of the NFPAs. We also investigated whether PTTG1, E-cadherin, and Ki-67, which are known to be related to each other, show a correlation with NFPA features.
Methods
A retrospective study was conducted on 87 patients with NPFAs who underwent surgical removal. The NFPAs were classified into three groups based on magnetic resonance imaging findings of suprasellar extension and cavernous sinus invasion. Immunohistochemical staining for PTTG1, PITX2, galectin-3, E-cadherin, and Ki-67 was performed on tissue microarrays.
Results
PTTG1 expression showed a statistically significant correlation with the invasiveness of NFPAs, whereas PITX2 and galectin-3 did not have a relationship with the invasiveness of NFPAs. Moreover, there was no association among PTTG1, E-cadherin, and Ki-67 expression.
Conclusions
PTTG1 has the potential to serve as a predictive biomarker for invasive NFPA. Furthermore, this study may serve as a reference for the development of PTTG1-targeted therapeutic agents.

Citations

Citations to this article as recorded by

High-throughput Screening for Cushing Disease: Therapeutic Potential of Thiostrepton via Cell Cycle Regulation
Takuro Hakata, Ichiro Yamauchi, Daisuke Kosugi, Taku Sugawa, Haruka Fujita, Kentaro Okamoto, Yohei Ueda, Toshihito Fujii, Daisuke Taura, Nobuya Inagaki
Endocrinology.2024;[Epub] CrossRef
Neoplasms and tumor-like lesions of the sellar region: imaging findings with correlation to pathology and 2021 WHO classification
Lorenzo Ugga, Raduan Ahmed Franca, Alessandra Scaravilli, Domenico Solari, Sirio Cocozza, Fabio Tortora, Luigi Maria Cavallo, Marialaura Del Basso De Caro, Andrea Elefante
Neuroradiology.2023; 65(4): 675. CrossRef
A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide
Prodromos Chatzikyriakou, Dimitria Brempou, Mark Quinn, Lauren Fishbein, Roberta Noberini, Ioannis N. Anastopoulos, Nicola Tufton, Eugenie S. Lim, Rupert Obholzer, Johnathan G. Hubbard, Mufaddal Moonim, Tiziana Bonaldi, Katherine L. Nathanson, Louise Izat
Clinical Epigenetics.2023;[Epub] CrossRef
Expression and clinical significance of Cathepsin K and MMPs in invasive non-functioning pituitary adenomas
Hongyan Liu, Saichun Zhang, Ting Wu, Zhaohui Lv, Jianming Ba, Weijun Gu, Yiming Mu
Frontiers in Oncology.2022;[Epub] CrossRef

Functional Inactivation of pRb Associated with Cyclin D1- and Cyclin-dependent Kinase 4 Overexpression Plays A Key Role in Human Pituitary Tumorigenesis.: Na Hye Myong; Korean J Pathol. 2009;43(1):56-62.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.56

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Abstract PDF

BACKGROUND
Human pituitary adenoma (PA) is a common intracranial tumor, but the mechanism underlying tumorigenesis has not been established. Functional inactivation of retinoblastoma protein (pRb) following cyclin D1- and cyclin-dependent kinase (CDK) 4-dependent hyperphosphorylation is one of the most important mechanisms in tumor cell proliferation. We evaluated immunohistochemical expressions of cyclin D1, CDK4 and phosphorylated pRb (p-pRb) in 50 PAs to investigate a role for functional inactivation of pRb associated with cyclin D1/CDK4 overexpression in pituitary tumorigenesis and to correlate it with clinicopathologic variables.
METHODS
Fifty human PAs were immunohistochemically stained for cyclin D1, CDK4 and p-pRb (Thr 356). Correlations between their expression and the clinicopathologic characteristics were statistically analyzed.
RESULTS
Cyclin D1 and CDK4 were overexpressed in 56% and 64%, respectively; pRb was hyperphosphorylated in 64%. Forty one cases (82%) showed one or more of these altered expressions. Overexpressions of cyclin D1 and CDK4 were correlated with functional pRb inactivation. Cyclin D1 overexpression was associated with apoplexy and growth hormone production.
CONCLUSIONS
Functional inactivation of pRb associated with the cyclin D1/CDK4 overexpression might play a key role in human pituitary tumorigenesis. CDK4 worked in concert with cyclin D1 to hyperphosphorylate pRb. Pituitary apoplexy appeared to be associated with cyclin D1 overexpression.

Citations

Citations to this article as recorded by

Differential expression of cyclin D1 in human pituitary tumors: relation to MIB-1 and p27/Kip1 labeling indices
Iman H. Hewedi, Wesam M. Osman, Manal M. El Mahdy
Journal of the Egyptian National Cancer Institute.2011; 23(4): 171. CrossRef

Comparison between Immunohistochemical Stains and Serum Hormone Level on Pituitary Adenomas.: Hye Seung Han, Yeon Lim Suh; Korean J Pathol. 1998;32(2):88-93.

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Abstract PDF: The current classification of pituitary adenomas is based on cell type, largely ascertained by immunohistochemistry and electron microscopy. In an application of immunohistochemistry, pathologists have some problems in judging the results. An immunostaining result does not always correspond with a serum hormone level. It is also difficult to determine the nature of a tumor when a few cells are positive. We performed the immunohistochemical stains on 34 pituitary adenomas using polyclonal antibodies to six pituitary hormones [PRL (prolactin), GH (growth hormone), ACTH (adrenocorticotropic hormone), FSH (follicle-stimulating hormone), LH (luteinizing hormone), TSH (thyroid-stimulating hormone)] and compared with serum hormone level. The serum hormone level was increased in 14 cases (41.2%) of PRL, 7 cases (20.6%) of PRL & GH, 6 pleurihormonal cases (17.6%), 4 nonfunctioning cases (11.8%), 2 cases (5.9%) of FSH, and 1 case (2.9%) of GH. The most common immunohistochemical type of pituitary adenoma was 10 prolactinoma cases (38.5%), followed by 7 pleurihormonal cases (26.9%), 4 null cell cases (15.4%), 3 cases of mixed PRL & GH (11.5%), 1 case of ACTH (3.8%) and 1 FSH & LH case (3.8%). The corresponding rates of the serum hormone level and immunostaining results were 94.1% in GH, 88.9% in TSH, 85.7% in LH, 82.4% in ACTH, 66.7% FSH, and 61.8% in PRL. In the immunostaining for FSH, 12 cases showed less than 5% positivity and most of them exhibited the normal serum hormone level. In conclusion, the most common elevated serum hormone and immunohistochemical type of pituitary adenoma was prolactinoma. The corresponding rate of the serum hormone level and immunostaining result was the highest in GH cell adenoma and was the lowest in prolactinoma. The cells showing less than 5% positivity seem to be entrapped normal cells.

Case Report

Mixed Gangliocytoma-Pituitary Adenoma: A case report.: Dong Sug Kim, Dae Hong Suh, Mi Jin Kim, O Lyong Kim; Korean J Pathol. 1998;32(2):138-141.

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Abstract PDF: The mixed gangliocytoma-pituitary adenoma is a very rare intracranial neoplasm, and it is frequently associated with endocrine symptoms; acromegaly, Cushing's disease, galactorrhea and amenorrhea. Morphologically it shows a mixture of gangliocytoma and pituitary adenoma in various proportions. In the area of gangliocytoma, there is no neoplastic glial component. The portion of pituitary adenoma consists mainly of chromophobe cells. There are three hypotheses in its histogenesis. We report a case of a 41 year-old lady presented with acromegaly and amenorrhea existing for 3 years. On magnetic resonance image, there is a dumbell-shaped mass in the sellar region. Histologically it showed typical features of mixed gangliocytoma-pituitary adenoma. This case is presented in the view of its rarity and interesting possible histogeneses.

Original Article

Immunohistochemical Study on Pituitary Aednoma.: Yong Hee Lee, Tai Seung Kim; Korean J Pathol. 1994;28(6):629-635.

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Abstract PDF: The development of immuohistochemistry and the application of electron microscopy have revolutionized our understanding of the pathopysiology of pituitart adenoma. The clinical value of functional characterization of pituitary adenoma has been realized. Immunohistochemical stains using polyclonal antibodies to six pituitary hormones (GH, PRL, ACTH, TSH, FSH & LH) were performed to classify the pituitary adenoma and to investigate the relationship between the results of the immunohistochemical study and pared to the serum hormone level. The results are summarized as follows: The Most common clinical type of pituitary adenoma was prolactinoma and the second was nonfunctioning adenoma. However, the most common immunohistological type of pituitary adenoma was null cell adenoma, the second one, lactotrope adenoma and the third one, mixed sommatotrope & lactotrope adenoma. In the clinically nonfunctioning adenoma cases, null cell adenoma were present in 75%; gonadotrope adenoma and corticotrope adenoma were present in 25%, while the serum prolactin level was increased in ten of the twenty cases(50%) of the null cell adenoma. When the serum prolactin level was increased above the 150ng/ml, the tumor cells gave positive reactions in 95.2% of cases immunohistochemically. But in the cases of GH, FSH & LH, the tumor cells gave positive reactions in 100%, 75%, and 66.7%, respectively. In the case of increased serum prolactin level, more than 50% and 30% proportion of tumor cells showed positive reactions in the micro- and macroadenoma, respectively.

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