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NETest in advanced high-grade gastroenteropancreatic neuroendocrine neoplasms

Sorbye, H. ; Hjortland, G. O. ; Vestermark, L. W. ; Sundlov, A. LU orcid ; Assmus, J. ; Couvelard, A. ; Perren, A. and Langer, S. W. (2024) In Journal of Neuroendocrinology 36(11).
Abstract

Molecular blood biomarkers are lacking for high-grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN). To histologically distinguish between neuroendocrine carcinoma (NEC), neuroendocrine tumors G3 (NET G3), adenocarcinoma and MINEN is often challenging. The mRNA-based NETest has diagnostic, prognostic and predictive value in neuroendocrine tumors G1-2 but has not been studied in HG GEP-NEN. Patients with advanced HG GEP-NEN were prospectively included in an observational study. A blood sample was collected before the start of chemotherapy and pseudonymised before NETest was performed. NETest results are expressed as an activity index (NETest score) from 0 to 100. The normal score cut-off is 20. Histological sections... (More)

Molecular blood biomarkers are lacking for high-grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN). To histologically distinguish between neuroendocrine carcinoma (NEC), neuroendocrine tumors G3 (NET G3), adenocarcinoma and MINEN is often challenging. The mRNA-based NETest has diagnostic, prognostic and predictive value in neuroendocrine tumors G1-2 but has not been studied in HG GEP-NEN. Patients with advanced HG GEP-NEN were prospectively included in an observational study. A blood sample was collected before the start of chemotherapy and pseudonymised before NETest was performed. NETest results are expressed as an activity index (NETest score) from 0 to 100. The normal score cut-off is 20. Histological sections were pseudonymised before centralized pathological re-evaluation. Samples from 60 patients were evaluable with the NETest. Main primary tumor sites were colon (14), rectum (12), pancreas (11) and esophagus (7). Re-classification: 30 NEC, 12 NET G3, 3 HG-NEN ambiguous morphology, 8 MiNEN, 3 adenocarcinomas with neuroendocrine differentiation (ADNE), 3 adenocarcinomas and 1 NET G2. Elevated NETest (>20) was seen in 38/45 (84%) HG GEP-NEN, all 17 large-cell NEC (100%), 11/13 (85%) small-cell NEC, all ambiguous cases and 7/12 (64%) NET G3. NETest was elevated in 5/8 (63%) MiNEN, 2/3 ADNE, however not in 3 adenocarcinomas. Median survival was 10.2 months (9.6–10.8 95%CI) for evaluable HG GEP-NEN treated with palliative chemotherapy (n = 39), and survival was significantly shorter in patients with NETest >60 with an OS of only 6.5 months. This is the first study to evaluate use of the NETest in advanced HG GEP-NEN. The NETest was almost always elevated in GEP-NEC and in all large-cell NEC. The NETest was also frequently elevated in NET G3 and MiNEN, however cases were limited. Baseline NETest was not predictive for benefit of chemotherapy, however a NETest >60 was prognostic with a shorter survival for patients receiving chemotherapy.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
gastroenteropancreatic, high-grade neuroendocrine neoplasms, NEC, NET G3, NETest
in
Journal of Neuroendocrinology
volume
36
issue
11
article number
e13428
publisher
Wiley-Blackwell
external identifiers
  • scopus:85197274235
  • pmid:38937137
ISSN
0953-8194
DOI
10.1111/jne.13428
language
English
LU publication?
yes
id
5b6136ac-a1d7-4bfd-848f-3bc34cf06aa6
date added to LUP
2024-12-12 10:59:09
date last changed
2025-07-11 04:07:42
@article{5b6136ac-a1d7-4bfd-848f-3bc34cf06aa6,
  abstract     = {{<p>Molecular blood biomarkers are lacking for high-grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN). To histologically distinguish between neuroendocrine carcinoma (NEC), neuroendocrine tumors G3 (NET G3), adenocarcinoma and MINEN is often challenging. The mRNA-based NETest has diagnostic, prognostic and predictive value in neuroendocrine tumors G1-2 but has not been studied in HG GEP-NEN. Patients with advanced HG GEP-NEN were prospectively included in an observational study. A blood sample was collected before the start of chemotherapy and pseudonymised before NETest was performed. NETest results are expressed as an activity index (NETest score) from 0 to 100. The normal score cut-off is 20. Histological sections were pseudonymised before centralized pathological re-evaluation. Samples from 60 patients were evaluable with the NETest. Main primary tumor sites were colon (14), rectum (12), pancreas (11) and esophagus (7). Re-classification: 30 NEC, 12 NET G3, 3 HG-NEN ambiguous morphology, 8 MiNEN, 3 adenocarcinomas with neuroendocrine differentiation (ADNE), 3 adenocarcinomas and 1 NET G2. Elevated NETest (&gt;20) was seen in 38/45 (84%) HG GEP-NEN, all 17 large-cell NEC (100%), 11/13 (85%) small-cell NEC, all ambiguous cases and 7/12 (64%) NET G3. NETest was elevated in 5/8 (63%) MiNEN, 2/3 ADNE, however not in 3 adenocarcinomas. Median survival was 10.2 months (9.6–10.8 95%CI) for evaluable HG GEP-NEN treated with palliative chemotherapy (n = 39), and survival was significantly shorter in patients with NETest &gt;60 with an OS of only 6.5 months. This is the first study to evaluate use of the NETest in advanced HG GEP-NEN. The NETest was almost always elevated in GEP-NEC and in all large-cell NEC. The NETest was also frequently elevated in NET G3 and MiNEN, however cases were limited. Baseline NETest was not predictive for benefit of chemotherapy, however a NETest &gt;60 was prognostic with a shorter survival for patients receiving chemotherapy.</p>}},
  author       = {{Sorbye, H. and Hjortland, G. O. and Vestermark, L. W. and Sundlov, A. and Assmus, J. and Couvelard, A. and Perren, A. and Langer, S. W.}},
  issn         = {{0953-8194}},
  keywords     = {{gastroenteropancreatic; high-grade neuroendocrine neoplasms; NEC; NET G3; NETest}},
  language     = {{eng}},
  number       = {{11}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Neuroendocrinology}},
  title        = {{NETest in advanced high-grade gastroenteropancreatic neuroendocrine neoplasms}},
  url          = {{http://dx.doi.org/10.1111/jne.13428}},
  doi          = {{10.1111/jne.13428}},
  volume       = {{36}},
  year         = {{2024}},
}