PITX2 as a Sensitive and Specific Marker of Midgut Neuroendocrine Tumors: Results from a Cohort of 1157 Primary Neuroendocrine Neoplasms

Grass A, Kasajima A, Foersch S, Kriegsmann M, Brobeil A, Schmitt M, Wagner D, Poppinga J, Wiese D, Maurer E, Kirschbaum A, Muley T, Winter H, Rinke A, Gress TM, Kremer M, Evert M, Märkl B, Quaas A, Eckstein M, Tschurtschenthaler M, Klöppel G, Denkert C, Bartsch DK, Jesinghaus M (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Modern Pathology Nature Publishing Group: Open Access Hybrid Model Option B

Book Volume: 37

Article Number: 100442

Journal Issue: 4

DOI: 10.1016/j.modpat.2024.100442

Abstract

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.

Authors with CRIS profile

Markus Eckstein Institute of Pathology

Involved external institutions

Philipps-Universität Marburg DE Germany (DE) Technische Universität München (TUM) DE Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) Städtisches Klinikum München DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE) Universitätsklinikum Augsburg DE Germany (DE) Universitätsklinikum Köln DE Germany (DE)

How to cite

APA:

Grass, A., Kasajima, A., Foersch, S., Kriegsmann, M., Brobeil, A., Schmitt, M.,... Jesinghaus, M. (2024). PITX2 as a Sensitive and Specific Marker of Midgut Neuroendocrine Tumors: Results from a Cohort of 1157 Primary Neuroendocrine Neoplasms. Modern Pathology, 37(4). https://dx.doi.org/10.1016/j.modpat.2024.100442

MLA:

Grass, Albert, et al. "PITX2 as a Sensitive and Specific Marker of Midgut Neuroendocrine Tumors: Results from a Cohort of 1157 Primary Neuroendocrine Neoplasms." Modern Pathology 37.4 (2024).

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