Double adenomas of the pituitary reveal distinct lineage markers, copy number alterations, and epigenetic profiles
Standard
Double adenomas of the pituitary reveal distinct lineage markers, copy number alterations, and epigenetic profiles. / Hagel, Christian; Schüller, Ulrich; Flitsch, Jörg; Knappe, Ulrich J; Kellner, Udo; Bergmann, Markus; Buslei, Rolf; Buchfelder, Michael; Rüdiger, Thomas; Herms, Jochen; Saeger, Wolfgang.
In: PITUITARY, Vol. 24, No. 6, 12.2021, p. 904-913.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Double adenomas of the pituitary reveal distinct lineage markers, copy number alterations, and epigenetic profiles
AU - Hagel, Christian
AU - Schüller, Ulrich
AU - Flitsch, Jörg
AU - Knappe, Ulrich J
AU - Kellner, Udo
AU - Bergmann, Markus
AU - Buslei, Rolf
AU - Buchfelder, Michael
AU - Rüdiger, Thomas
AU - Herms, Jochen
AU - Saeger, Wolfgang
N1 - © 2021. The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - PURPOSE: Pituitary adenoma (PA) constitutes the third most common intracranial neoplasm. The mostly benign endocrine lesions express no hormone (null cell PA) or the pituitary hormone(s) of the cell lineage of origin. In 0.5-1.5% of surgical specimens and in up to 10% of autopsy cases, two or three seemingly separate PA may coincide. These multiple adenomas may express different hormones, but whether or not expression of lineage-restricted transcription factors and molecular features are distinct within multiple lesions remains unknown.METHODS: Searching the data bank of the German Pituitary Tumor Registry 12 double pituitary adenomas with diverse lineage were identified among 3654 adenomas and 6 hypophyseal carcinomas diagnosed between 2012 and 2020. The double adenomas were investigated immunohistochemically for expression of hormones and lineage markers. In addition, chromosomal gains and losses as well as global DNA methylation profiles were assessed, whenever sufficient material was available (n = 8 PA).RESULTS: In accordance with the literature, combinations of GH/prolactin/TSH-FSH/LH adenoma (4/12), GH/prolactin/TSH-ACTH adenoma (3/12), and ACTH-FSH/LH adenoma (3/12) were observed. Further, two out of 12 cases showed a combination of a GH/prolactin/TSH adenoma with a null-cell adenoma. Different expression pattern of hormones were confirmed by different expression of transcription factors in 11/12 patients. Finally, multiple lesions that were molecularly analysed in 4 patients displayed distinct copy number changes and global methylation pattern.CONCLUSION: Our data confirm and extend the knowledge on multiple PA and suggest that such lesions may origin from distinct cell types.
AB - PURPOSE: Pituitary adenoma (PA) constitutes the third most common intracranial neoplasm. The mostly benign endocrine lesions express no hormone (null cell PA) or the pituitary hormone(s) of the cell lineage of origin. In 0.5-1.5% of surgical specimens and in up to 10% of autopsy cases, two or three seemingly separate PA may coincide. These multiple adenomas may express different hormones, but whether or not expression of lineage-restricted transcription factors and molecular features are distinct within multiple lesions remains unknown.METHODS: Searching the data bank of the German Pituitary Tumor Registry 12 double pituitary adenomas with diverse lineage were identified among 3654 adenomas and 6 hypophyseal carcinomas diagnosed between 2012 and 2020. The double adenomas were investigated immunohistochemically for expression of hormones and lineage markers. In addition, chromosomal gains and losses as well as global DNA methylation profiles were assessed, whenever sufficient material was available (n = 8 PA).RESULTS: In accordance with the literature, combinations of GH/prolactin/TSH-FSH/LH adenoma (4/12), GH/prolactin/TSH-ACTH adenoma (3/12), and ACTH-FSH/LH adenoma (3/12) were observed. Further, two out of 12 cases showed a combination of a GH/prolactin/TSH adenoma with a null-cell adenoma. Different expression pattern of hormones were confirmed by different expression of transcription factors in 11/12 patients. Finally, multiple lesions that were molecularly analysed in 4 patients displayed distinct copy number changes and global methylation pattern.CONCLUSION: Our data confirm and extend the knowledge on multiple PA and suggest that such lesions may origin from distinct cell types.
U2 - 10.1007/s11102-021-01164-1
DO - 10.1007/s11102-021-01164-1
M3 - SCORING: Journal article
C2 - 34478014
VL - 24
SP - 904
EP - 913
JO - PITUITARY
JF - PITUITARY
SN - 1386-341X
IS - 6
ER -