WDNET
Dotaz
Zobrazit nápovědu
HoxB13 is a transcription factor involved in defining of posterior endodermal derivatives, including prostate and rectum. While it is used as a marker of prostatic adenocarcinoma, it has not been studied systematically in neuroendocrine neoplasms. Thus, we performed HoxB13 immunohistochemistry in tissue microarrays and the whole sections of 232 neuroendocrine neoplasms. These included 34 paragangliomas (PGs), 20 cauda equina neuroendocrine tumors (CENETs), 123 well-differentiated neuroendocrine tumors (WDNETs), and 55 neuroendocrine carcinomas (NECs). WDNETs were additionally analyzed with SATB2, and colorectal WDNETs with CDX2 and serotonin immunohistochemistry. In total, HoxB13 immunoreactivity was observed in 95% (19/20) CENETs, 10.6% (13/123) WDNETs, and 12.9% (7/54) NECs. No PGs were positive. Large intestine WDNETs expressed HoxB13 in 68.4% (13/19); five negative tumors originated in cecum and one in rectum. In rectum, 92.9% (13/14) WDNETs expressed HoxB13. HoxB13 was 92.9% sensitive and 100% specific, showing 100% positive predictive value for the rectal origin of WDNET. In NECs, HoxB13 was positive in 15.4% (2/13) GIT tumors and 80% (4/5) prostatic NECs, but in none of urinary bladder NECs (0/8). SATB2 was positive in 17.1% (21/123) WDNETs, including 78.9% (15/19) of colorectal WDNETs, 71.4% (5/7) appendiceal WDNETs, and 2.9% (1/34) small intestine WDNETs. All 4 SATB2-negative large bowel tumors originated in the cecum. When both markers combined, HoxB13+/SATB2+ immunoprofile was seen exclusively in rectal WDNETs (positive predictive value 100%), while HoxB13-/SATB2+ immunoprofile was highly suggestive of the appendiceal origin (positive predictive value 71.4%). Therefore, HoxB13 can be useful as an immunohistochemical marker of rectal WDNETs and prostatic NECs.
- MeSH
- homeodoménové proteiny MeSH
- kolorektální nádory * MeSH
- lidé MeSH
- nádorové biomarkery MeSH
- nádory močového měchýře * MeSH
- nádory rekta * diagnóza patologie MeSH
- neuroendokrinní karcinom * diagnóza MeSH
- neuroendokrinní nádory * diagnóza patologie MeSH
- transkripční faktory MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Phox2B is a transcription factor responsible for chromaffin cell phenotype. Although it is used routinely for diagnosis of neuroblastoma, previous reports concerning its utility in the diagnosis of neuroendocrine neoplasms have been conflicting. We assessed Phox2b immunoreactivity in different neuroendocrine neoplasms. Tissue microarrays or whole sections of 36 paragangliomas (PGs), 91 well-differentiated neuroendocrine tumours of different organs (WDNETs), 31 neuroendocrine carcinomas (NECs), and 6 olfactory neuroblastomas (ONBs) were stained with Phox2B antibody (EP312) and GATA3. The percentage of positive cells and intensity was analysed using H-score. Phox2B immunoreactivity was seen in 97.2% (35/36) PGs, 11% (10/91) WDNETs, 9.7% (3/31) NECs, and 16.7% (1/6) ONBs. PGs were significantly more often positive (p < 0.001, χ2) than other neuroendocrine tumours, showing highest H-score (mean 144.9, SD ± 75.1) and percentage of positive cells (median 81.3%, IQR 62.5-92.5%). Compared to Phox2B-positive WDNETs, PGs showed significantly higher H-score (median 145 vs 7.5, p < 0.001) and percentage of positive cells (median 82.5% vs 4.5%, p < 0.001). Phox2B positivity was 97.2% sensitive and 89% specific for the diagnosis of PG. GATA3 was 100% sensitive and 88% specific for the diagnosis of PG. When combined, any Phox2B/GATA3 coexpression was 97.1% sensitive and 99.1% specific for the diagnosis of paraganglioma. Widespread Phox2B immunoreactivity is a highly characteristic feature of PGs and it can be used as an additional marker in differential diagnosis of neuroendocrine tumours.
Hand2 is a core transcription factor responsible for chromaffin cell differentiation. However, its potential utility in surgical pathology has not been studied. Thus, we aimed to investigate its expression in paragangliomas, other neuroendocrine neoplasms (NENs), and additional non-neuroendocrine tumors. We calibrated Hand2 immunohistochemistry on adrenal medulla cells and analyzed H-scores in 46 paragangliomas (PGs), 9 metastatic PGs, 21 cauda equina neuroendocrine tumors (CENETs), 48 neuroendocrine carcinomas (NECs), 8 olfactory neuroblastomas (ONBs), 110 well-differentiated NETs (WDNETs), 10 adrenal cortical carcinomas, 29 adrenal cortical adenomas, 8 melanomas, 41 different carcinomas, and 10 gastrointestinal stromal tumors (GISTs). Both tissue microarrays (TMAs) and whole sections (WSs) were studied. In 171 NENs, previously published data on Phox2B and GATA3 were correlated with Hand2. Hand2 was positive in 98.1% (54/55) PGs, but only rarely in WDNETs (9.6%, 10/104), CENETs (9.5%, 2/21), NECs (4.2%, 2/48), or ONBs (12.5%, 1/8). Any Hand2 positivity was 98.1% sensitive and 91.7% specific for the diagnosis of PG. The Hand2 H-score was significantly higher in primary PGs compared to Hand2-positive WDNETs (median 166.3 vs. 7.5; p < 0.0001). Metastatic PGs were positive in 88.9% (8/9). No Hand2 positivity was observed in any adrenal cortical neoplasm or other non-neuroendocrine tumors, with exception of 8/10 GISTs. Parasympathetic PGs showed a higher Hand2 H-score compared to sympathetic PGs (median H-scores 280 vs. 104, p < 0.0001). Hand2 positivity in NENs serves as a reliable marker of primary and metastatic PG, since other NENs only rarely exhibit limited Hand2 positivity.
