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TTF-1 Negative NSCLC — SCE Medical Oncology MCQ

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HardLung CancerTTF-1 Negative NSCLCSCE Medical Oncology

A metastatic tumour is morphologically compatible with pulmonary adenocarcinoma but TTF-1 is negative. Imaging and a broader immunohistochemical panel support lung origin, and comprehensive molecular profiling is pending. How should TTF-1 negativity influence management?

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Correct answer: C — Treat it as adverse prognostic information, not proof of another primary or a validated reason to omit molecular profiling

Explanation lettering: E = shown as A · D = shown as B · A = shown as C · B = shown as D · C = shown as E

A is correct. TTF-1-negative pulmonary adenocarcinoma is recognised and has repeatedly shown poorer outcomes in retrospective cohorts, including during pemetrexed-based therapy. These data are prognostic and hypothesis-generating rather than a validated binary prescribing rule. TTF-1 negativity broadens the differential, so organ of origin requires morphology, the rest of the immunopanel and imaging; it does not automatically mean squamous or gastrointestinal cancer. It neither proves immunotherapy resistance nor excludes an actionable driver, so comprehensive molecular testing and PD-L1 assessment remain necessary.

Reference: TTF-1-negative advanced pulmonary adenocarcinoma cohort: https://pubmed.ncbi.nlm.nih.gov/29948461/