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4 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Invasive mucinous adenocarcinoma is a type of lung cancer whose cells look like stomach or bowel lining and fill the air spaces with mucus, often appearing as pneumonia-like shadows on a scan. Most cases carry a KRAS mutation, and many of the rest carry a gene fusion, including NRG1, that new drugs can target.
The IASLC/ATS/ERS classification of 2011 separated invasive mucinous adenocarcinoma from the non-mucinous lepidic tumours because of its distinct cells (goblet or columnar with abundant mucin), its tendency to spread through the airways as multifocal or lobar consolidation, and its biology (Travis 2011). Sequencing of 72 cases found KRAS mutations in 63 percent, with a distribution of nucleotide changes closer to gastrointestinal than to other lung tumours; among the KRAS wild-type cases were the fusions CD74-NRG1, VAMP2-NRG1, TRIM4-BRAF, TPM3-NTRK1 and EML4-ALK and mutations in ERBB2 and other genes (Shim 2015). Expression profiling identified a 143-gene mucinous signature, shared with mucin-producing gastrointestinal, pancreatic and breast cancers, in which the transcription factors FOXA3, SPDEF and HNF4A drive MUC5AC and MUC5B, and in which the checkpoint VTCN1 rather than PD-L1 is expressed (EMBO Molecular Medicine 2017).
How it differs from its parent: it is TTF-1-negative and expresses gut markers, so it can be mistaken for a metastasis; it is EGFR-mutant only rarely; and it is the lung cancer richest in NRG1 fusions, for which the HER2-HER3 bispecific antibody zenocutuzumab is approved.
| Setting | Approach | Guideline |
|---|---|---|
| All stages | Treated as lung adenocarcinoma by stage, with KRAS G12C inhibitors, zenocutuzumab for NRG1 fusions and matched inhibitors for other fusions when found. | not mapped |