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- Molecular Subtyping of Circulating Tumor Cells in Patients with Small Cell Lung Cancer

# Molecular Subtyping of Circulating Tumor Cells in Patients with Small Cell Lung Cancer

A proposed molecular classification of small cell lung cancer turns on four transcription factors normally read from tumor tissue, which this disease rarely yields; this AACR 2022 poster reports an immunofluorescence assay that reads all four on circulating tumor cells from blood, across 28 patients.

Presented by Vanderbilt University Medical Center.

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- All four subtype-defining transcription factors were read on circulating tumor cells rather than on tumor tissue. The neuroendocrine markers ASCL1 and NEUROD1 and the non-neuroendocrine markers YAP1 and POU2F3 were co-stained alongside the CTC markers across two marker sets, in blood drawn from 28 patients with small cell lung cancer; CTCs were detected in 20 of 28 (71%) of them.

- Every positivity rate is conditioned on the patients whose CTCs were actually found, and the denominators are not all the same. Among the 20 patients with detectable CTCs, ASCL1 was positive in 16 of 20 (80%) and NEUROD1 in 11 of 20 (55%), while YAP1 was positive in 9 of 18 (50%) and POU2F3 in 12 of 18 (67%) of the samples assessed for the non-neuroendocrine pair.

- Serial draws tracked how the markers moved as the disease progressed, which is the reason to read them in blood at all. Samples were collected at treatment-naive, on-treatment and relapsed timepoints, at a median of 4 collections per patient; of the three relapse samples analysed at the time of presentation, 2 of 3 carried rising CTC counts with falling ASCL1 expression, and the third lost every marker in the few CTCs still detected. Marker expression on CTCs here is investigational, not a validated subtype call and not a basis for selecting treatment.

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