Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): The NORDIC NEC study

Sørbye, Halfdan; Welin, Staffan; Langer, Seppo W.; Vestermark, Lene Weber; Holt, Nanna; Österlund, Pia; Dueland, Svein; Hofsli, Eva; Guren, Marianne G.; Ӧhrling, Katarina; Birkemeyer, Elke; Thiis‐Evensen, Espen; Biagini, Matteo; Grønbæk, Henning; Soveri, Leena‐Maija; Olsen, I; Federspiel, Birgitte; Assmus, J; Janson, Eva Tiensuu; Knigge, Ulrich

doi:10.1093/annonc/mds276

Cited by 847 publications

(1,095 citation statements)

References 32 publications

Supporting

Mentioning

976

Contrasting

Unclassified

Order By: Relevance

“…Carcinomas were divided into two groups using a cut-off value of 55% that was calculated with a model-based cluster algorithm (Fraley & Raftery 2002). This threshold value corresponded exactly to that used by Sorbye et al (2013). More precisely, 80% of MSI-and 72.3% of MSS-cancers showed a Ki67 R55%; the mean value of the Ki67 index was 68.4% for MSI and 63.6% for MSS NEC-MANECs.…”

Section: Msi Gep Nec/manecsmentioning

confidence: 99%

Microsatellite unstable gastrointestinal neuroendocrine carcinomas: a new clinicopathologic entity

Sahnane¹,

Furlan²,

Monti³

et al. 2014

Endocrine-Related Cancer

137

131

View full text Add to dashboard Cite

Gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) and mixed adenoneuroendocrine carcinomas (MANECs) are heterogeneous neoplasms characterized by poor outcome. Microsatellite instability (MSI) has recently been found in colorectal NECs showing a better prognosis than expected. However, the frequency of MSI in a large series of GEP-NEC/MANECs is still unknown. In this work, we investigated the incidence of MSI in GEP-NEC/MANECs and characterized their clinicopathologic and molecular features. MSI analysis and immunohistochemistry for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) were performed in 89 GEP-NEC/MANECs (six esophageal, 77 gastrointestinal, three pancreatic, and three of the gallbladder). Methylation of 34 genes was studied by methylation-specific multiplex ligation probe amplification. Mutation analysis of BRAF and KRAS was assessed by PCR-pyrosequencing analysis. MSI was observed in 11 NEC/MANECs (12.4%): seven intestinal and four gastric. All but two MSI-cases showed MLH1 methylation and loss of MLH1 protein. The remaining two MSI-cancers showed lack of MSH2 or PMS2 immunohistochemical expression. MSI-NEC/MANECs showed higher methylation levels than microsatellite stable NEC/MANECs (40.6% vs 20.2% methylated genes respectively, P!0.001). BRAF mutation was detected in six out of 88 cases (7%) and KRAS mutation was identified in 15 cases (17%). BRAF mutation was associated with MSI (P!0.0008), while KRAS status did not correlate with any clinicopathologic or molecular feature. Vascular invasion (PZ0.0003) and MSI (PZ0.0084) were identified as the only independent prognostic factors in multivariate analysis. We conclude that MSI identifies a subset of gastric and intestinal NEC/MANECs with distinct biology and better prognosis. MSI-NEC/MANECs resemble MSI-gastrointestinal adenocarcinomas for frequency, molecular profile and pathogenetic mechanisms.

show abstract

Section: Msi Gep Nec/manecsmentioning

confidence: 99%

Microsatellite unstable gastrointestinal neuroendocrine carcinomas: a new clinicopathologic entity

Sahnane¹,

Furlan²,

Monti³

et al. 2014

Endocrine-Related Cancer

137

131

View full text Add to dashboard Cite

show abstract

“…Running through therapy-oriented studies on EPNEC available in the literature, it can be concluded that the treatment of EPNEC of the small cell type does not differ from the pulmonary counterpart [62][63][64] with response rates and global prognosis in general overlapping with those reported for lung SCC, even though some authors reported poorer results [65]. Since LCNECs of the lung, at least in their advanced stage, are also treated similarly to SCC [66], the whole spectrum of EPNEC generally undergoes the same chemotherapy approach.…”

Section: Issue 1 221 Problem: How To Label These Tumors?mentioning

confidence: 99%

“…Since LCNECs of the lung, at least in their advanced stage, are also treated similarly to SCC [66], the whole spectrum of EPNEC generally undergoes the same chemotherapy approach. Indeed, some reports indicate that despite that the chemotherapy protocols are quite similar, response to therapy is different and the stability of disease after completion of chemotherapy may follow a different course [61,63,67].…”

Section: Issue 1 221 Problem: How To Label These Tumors?mentioning

confidence: 99%

“…Solution: Assess proliferation index in all cases; in the future, personalized treatments are expected. In the large series of GEP NEC analyzed in the NORDIC study [63] a negative prognostic role of performance status, colorectal primary, elevated platelet, and lactose dehydrogenase (LDH) levels was observed. Proliferation index differed in terms of impact on survival and response to chemotherapy.…”

Section: Issue 1 221 Problem: How To Label These Tumors?mentioning

confidence: 99%

See 1 more Smart Citation

Extrapulmonary neuroendocrine small and large cell carcinomas: a review of controversial diagnostic and therapeutic issues

et al. 2014

View full text Add to dashboard Cite

Summary Extrapulmonary neuroendocrine carcinoma (EPNEC) is a heterogeneous and rare group of high-grade neoplasms occurring in different organs. They usually share a poor prognosis, but diagnostic and therapeutic options still include several controversial issues, due to the rarity of this condition and to differences in architecture and cell size, being some cases pure small cell carcinomas, other pure large cell neuroendocrine carcinomas and some others combined/mixed neuroendocrine carcinomas with a conventional non-neuroendocrine carcinoma. In addition, the therapeutic strategy varies in different organs (surgery and/or chemotherapy and/or radiation therapy and/or targeted treatments), and clinicians and pathologists are asked to interact to reach an accurate classification of every single case, as well as the most appropriate selection of the treatment options, even considering different time points of each EPNEC natural history. This overview highlights controversial pathological and clinical issues and summarizes possible solutions to most of such EPNEC-related problems.

show abstract

“…Although G3 welldifferentiated GEP-NETs are more aggressive than G1 and G2 GEP-NETs, they are not as aggressive as true poorly differentiated neuroendocrine carcinomas. Most importantly, the G3 well-differentiated GEP-NETs do not respond as well to platinum/etoposide chemotherapy normally used for small cell carcinomas and other related neoplasms [13]. This subgroup is quite uncommon, most reported examples arising in the pancreas; however, the clinical differences between G3 well-differentiated GEPNETs and poorly differentiated neuroendocrine carcinomas suggest that it would indeed be worthwhile to re-evaluate high-grade cases lacking clear documentation of differentiation status.…”

mentioning

confidence: 99%

Reassessing the grade of gastroenteropancreatic neuroendocrine neoplasms

Klimstra

2016

Endocrine

View full text Add to dashboard Cite

Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): The NORDIC NEC study

Cited by 847 publications

References 32 publications

Microsatellite unstable gastrointestinal neuroendocrine carcinomas: a new clinicopathologic entity

Microsatellite unstable gastrointestinal neuroendocrine carcinomas: a new clinicopathologic entity

Extrapulmonary neuroendocrine small and large cell carcinomas: a review of controversial diagnostic and therapeutic issues

Reassessing the grade of gastroenteropancreatic neuroendocrine neoplasms

Contact Info

Product

Resources

About