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

被引:5
作者
Grass, Albert [1 ,2 ]
Kasajima, Atsuko [3 ]
Foersch, Sebastian [4 ]
Kriegsmann, Mark [5 ]
Brobeil, Alexander [5 ]
Schmitt, Maxime [1 ,2 ]
Wagner, Daniel [4 ]
Poppinga, Jelte [2 ,6 ]
Wiese, Dominik [2 ,6 ]
Maurer, Elisabeth [2 ,6 ]
Kirschbaum, Andreas [2 ,6 ]
Muley, Thomas [7 ,8 ]
Winter, Hauke [7 ,8 ,9 ]
Rinke, Anja [2 ,10 ]
Gress, Thomas M. [2 ,10 ]
Kremer, Markus [11 ]
Evert, Matthias [12 ]
Maerkl, Bruno [13 ]
Quaas, Alexander [14 ]
Eckstein, Markus [15 ]
Tschurtschenthaler, Markus [16 ]
Kloeppel, Guenter [3 ]
Denkert, Carsten [1 ,2 ]
Bartsch, Detlef K. [2 ,6 ]
Jesinghaus, Moritz [1 ,2 ]
机构
[1] Phillips Univ Marburg, Dept Pathol, Marburg, Germany
[2] Univ Hosp Marburg, Marburg, Germany
[3] Tech Univ Munich, Dept Pathol, Munich, Germany
[4] Univ Hosp Mainz, Dept Pathol, Mainz, Germany
[5] Univ Hosp Heidelberg, Dept Pathol, Heidelberg, Germany
[6] Phillips Univ Marburg, Dept Surg, Marburg, Germany
[7] Translat Lung Res Ctr Heidelberg TLRC H, Heidelberg, Germany
[8] Heidelberg Univ Hosp, Translat Res Unit, Thoraxklin, Heidelberg, Germany
[9] Heidelberg Univ Hosp, Dept Thorac Surg, Thoraxklin, Heidelberg, Germany
[10] Phillips Univ Marburg, Dept Gastroenterol Endocrinol & Infect Dis, Marburg, Germany
[11] Stadt Klinikum Munchen, Inst Pathol, Munich, Germany
[12] Univ Hosp Regensburg, Dept Pathol, Regensburg, Germany
[13] Univ Hosp Augsburg, Inst Pathol, Augsburg, Germany
[14] Univ Hosp Cologne, Inst Pathol, Cologne, Germany
[15] Friedrich Alexander Univ Erlangen Nurnberg, Dept Pathol, Univ Hosp Erlangen, Erlangen, Germany
[16] German Canc Consortium DKTK, Inst Translat Canc Res, Partner Site Munich, Munich, Germany
关键词
midgut; neuroendocrine carcinoma; neuroendocrine neoplasms; neuroendocrine tumor; Pituitary Homeobox 2; CLASSIFICATION; CARCINOIDS; CDX-2; TTF-1; IRS;
D O I
10.1016/j.modpat.2024.100442
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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. (c) 2024 THE AUTHORS. Published by Elsevier Inc. on behalf of the United States & Canadian Academy of Pathology. This is an open access article under the CC BY -NC -ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).
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页数:10
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