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PITX2 as a sensitive and specific marker of midgut neuroendocrine tumors: results from a cohort of 1157 primary neuroendocrine neoplasms

As neuroendocrine tumors (NETs) often present as metastatic lesions, immunohistochemical assignment to a site of origin is one of the most important tasks in their pathologic assessment. Because a fraction of NETs eludes the typical expression profiles of their primary localization, additional sensi...

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Main Authors: Grass, Albert (Author) , Kasajima, Atsuko (Author) , Foersch, Sebastian (Author) , Kriegsmann, Mark (Author) , Brobeil, Alexander (Author) , Schmitt, Maxime (Author) , Wagner, Daniel (Author) , Poppinga, Jelte (Author) , Wiese, Dominik (Author) , Maurer, Elisabeth (Author) , Kirschbaum, Andreas (Author) , Muley, Thomas (Author) , Winter, Hauke (Author) , Rinke, Anja (Author) , Gress, Thomas M. (Author) , Kremer, Markus (Author) , Evert, Matthias (Author) , Märkl, Bruno (Author) , Quaas, Alexander (Author) , Eckstein, Markus (Author) , Tschurtschenthaler, Markus (Author) , Klöppel, Günter (Author) , Denkert, Carsten (Author) , Bartsch, Detlef K. (Author) , Jesinghaus, Moritz (Author)
Format: Article (Journal)
Language:English
Published: April 2024
In: Modern pathology
Year: 2024, Volume: 37, Issue: 4, Pages: 1-10
ISSN:1530-0285
DOI:10.1016/j.modpat.2024.100442
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.modpat.2024.100442
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S089339522400022X
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Author Notes:Albert Grass, Atsuko Kasajima, Sebastian Foersch, Mark Kriegsmann, Alexander Brobeil, Maxime Schmitt, Daniel Wagner, Jelte Poppinga, Dominik Wiese, Elisabeth Maurer, Andreas Kirschbaum, Thomas Muley, Hauke Winter, Anja Rinke, Thomas M. Gress, Markus Kremer, Matthias Evert, Bruno Märkl, Alexander Quaas, Markus Eckstein, Markus Tschurtschenthaler, Günter Klöppel, Carsten Denkert, Detlef K. Bartsch, Moritz Jesinghaus
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Summary:As neuroendocrine tumors (NETs) often present as metastatic lesions, immunohistochemical assignment to a site of origin is one of the most important tasks in their pathologic assessment. Because a fraction of NETs eludes the typical expression profiles of their primary localization, additional sensitive and specific markers are required to improve diagnostic certainty. We investigated the expression of the transcription factor Pituitary Homeobox 2 (PITX2) in a large-scale cohort of 909 NET and 248 neuroendocrine carcinomas (NEC) according to the immunoreactive score (IRS) and correlated PITX2 expression groups with general tumor groups and primary localization. PITX2 expression (all expression groups) was highly sensitive (98.1%) for midgut-derived NET, but not perfectly specific, as non-midgut NET (especially pulmonary/duodenal) were quite frequently weak or moderately positive. The specificity rose to 99.5% for a midgut origin of NET if only a strong PITX2 expression was considered, which was found in only 0.5% (one pancreatic/one pulmonary) of non-midgut NET. In metastases of midgut-derived NET, PITX2 was expressed in all cases (87.5% strong, 12.5% moderate), whereas CDX2 was negative or only weakly expressed in 31.3% of the metastases. In NEC, a fraction of cases (14%) showed a weak or moderate PITX2 expression, which was not associated with a specific tumor localization. Our study independently validates PITX2 as a very sensitive and specific immunohistochemical marker of midgut-derived NET in a very large collective of neuroendocrine neoplasms. Therefore, our data argue toward implementation into diagnostic panels applied for NET as a firstline midgut marker.
Item Description:Online verfügbar 1 February 2024, Version des Artikels 26 February 2024
Gesehen am 01.07.2024
Physical Description:Online Resource
ISSN:1530-0285
DOI:10.1016/j.modpat.2024.100442

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