Abstract
Introduction:
Stage IV large cell neuroendocrine carcinoma (LCNEC) of the lung generally presents as disseminated and aggressive disease with a Ki-67 proliferation index (PI) 40–80%. LCNEC can be subdivided in two main subtypes: the first harboring TP53/RB1 mutations (small-cell lung carcinoma (SCLC)-like), the second with mutations in TP53 and STK11/KEAP1 (non-small-cell lung carcinoma (NSCLC)-like). Here we evaluated 11 LCNEC patients with only a solitary brain metastasis and evaluate phenotype, genotype and follow-up.
Methods:
Eleven LCNEC patients with solitary brain metastases were analyzed. Clinical characteristics and survival data were retrieved from medical records. Pathological analysis included histomorphological analysis, immunohistochemistry (pRB and Ki-67 PI) and next-generation sequencing (TP53, RB1, STK11, KEAP1 and MEN1).
Results:
All patients had N0 or N1 disease. Median overall survival (OS) was 12 months (95% confidence interval (CI) 5.5–18.5 months). Mean Ki-67 PI was 59% (range 15–100%). In 6/11 LCNEC Ki-67 PI was ≤40%. OS was longer for Ki-67 ≤40% compared to >40% (17 months (95% CI 11–23 months) vs 5 months (95% CI 0.7–9 months), P = 0.007). Two patients were still alive at follow-up after 86 and 103 months, both had Ki-67 ≤40%. 8/11 patients could be subclassified, and both SCLC-like (n = 6) and NSCLC-like (n = 2) subtypes were present. No MEN1 mutation was found.
Conclusion:
Stage IV LCNEC with a solitary brain metastasis and N0/N1 disease show in the majority of cases Ki-67 PI ≤40% and prolonged survival, distinguishing them from general LCNEC. This unique subgroup can be both of the SCLC-like and NSCLC-like subtype.
| Original language | English |
|---|---|
| Pages (from-to) | 1600-1606 |
| Number of pages | 7 |
| Journal | Endocrine Connections |
| Volume | 8 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2019 |
Bibliographical note
Funding Information:B C M H reports grants from Bristol-Myers Squibb, non-financial support from Abbvie, outside the submitted work. J L D reports personal fees from BMS, personal fees from Pfizer, personal fees from Boehringer-阀ngelheim, personal fees from Novartis, personal fees from Ipsen, outside the submitted work. E J M S reports grants from Bristol-Myers Squibb, Astra Zeneca, Pfizer, Novartis and MSD, personal fees from AbbVie and Roche, non-financial support from Abbvie, outside the submitted work. A-M C D reports grants from Bristol-Myers Squibb, personal fees from Roche, BMS, Eli Lily, Takeda and Boehringer 阀ngelheim, non-financial support from Abbvie, outside the submitted work. The other authors have nothing to disclose.
Publisher Copyright:
© 2019 The authors Published by Bioscientifica Ltd.
