Lung adenocarcinoma with neuroendocrine differentiation: Molecular markers testing and treatment outcomes

J Formos Med Assoc. 2023 Aug;122(8):731-737. doi: 10.1016/j.jfma.2022.12.011. Epub 2022 Dec 30.

Abstract

Background: Among the histologic types of lung cancer, adenocarcinoma is the most common. Moreover, lung adenocarcinoma with neuroendocrine differentiation (LANED) is a rare histologic character. So far, the clinical significance remains unclear.

Material and methods: We searched for the patients diagnosed with LANED from the electronic pathology database between January 2000 and June 2020 in a tertiary hospital. The tumor specimens were reviewed by a pathologist to confirm the diagnosis. EGFR mutation, ALK translocation, as well as programmed death ligand 1 (PD-L1) and rearranged during transfection (RET) expression were tested in the specimens of LANED. The clinical data were also collected and analyzed.

Results: A total of 10 patients diagnosed with LANED were included. Most were male (80%) and ever smokers (70%). The median age was 71.5 years old. At diagnosis, most had tumors harboring no EGFR mutation (70%), negative ALK translocation (88.9%), and without PD-L1 expression (90%). All specimens tested by immunohistochemical staining for RET expression (n = 9) showed positive results. Among the 10 patients, five underwent operation (stage I, n = 4; stage II, n = 1). The patient with stage II disease had recurrence 11 months later. For patients with advanced stages (stage III, n = 1; stage IV, n = 4), the treatment modalities varied and the overall survival ranged from 11.0 to 46.7 months.

Conclusion: LANED might be associated with a high proportion of RET expression, whereas EGFR mutation, ALK alteration, and PD-L1 expression were uncommon. Further large-scale prospective studies on molecular testing profile and clinical significance of LANED are warranted.

Keywords: Adenocarcinoma; Chemotherapy; Lung cancer; Neuroendocrine differentiation; Overall survival.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma* / diagnosis
  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / therapy
  • Aged
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • B7-H1 Antigen / therapeutic use
  • Biomarkers
  • Female
  • Humans
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / therapy
  • Male
  • Mutation
  • Prospective Studies
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / therapeutic use
  • Treatment Outcome

Substances

  • B7-H1 Antigen
  • Biomarkers
  • Receptor Protein-Tyrosine Kinases