{"entity":{"id":"ttf1-p40","kind":"term","name":"TTF-1 and p40 (how lung histology is decided)","aka":["TTF-1","TTF1","p40","thyroid transcription factor 1","TTF-1 and p40 panel","NSCLC-NOS"],"tldr":"The two stains that decide whether a poorly differentiated lung cancer is called adenocarcinoma or squamous cell carcinoma. TTF-1 positive with p40 negative means adenocarcinoma; p40 positive with TTF-1 negative means squamous. The answer decides whether the tumour is sequenced and which drugs are safe.","summary":"Most lung cancers are diagnosed on a small biopsy or a cytology sample, not on a resection, and many of those tumours are too poorly differentiated for morphology alone to assign a type. The 2021 WHO classification keeps the order of evidence, morphology first, immunohistochemistry to support it, molecular tests last, and adds a section devoted to classifying small diagnostic samples, because that is where most of the decisions are made. In practice a minimal panel of two markers does the work: thyroid transcription factor 1 (TTF-1) marks adenocarcinoma of the lung, and p40, an isoform of p63, marks squamous cell carcinoma. A tumour positive for one and negative for the other is reported as that type, rather than as non-small-cell carcinoma not otherwise specified, and the panel is kept small deliberately so that tissue is left for molecular testing. The label is not cosmetic. Adenocarcinoma and non-squamous tumours are sequenced for EGFR, ALK, ROS1, BRAF, MET, RET, NTRK, KRAS and HER2, and squamous tumours usually are not, because those drivers are rare in them. Pemetrexed and bevacizumab are used in non-squamous disease and avoided in squamous disease, the latter because of fatal haemorrhage. A tumour that stains for neither is left as non-small-cell carcinoma not otherwise specified, and a tumour with neuroendocrine morphology needs a different panel again.","asOf":"2026-09-25","wikipedia":"https://en.wikipedia.org/wiki/Thyroid_transcription_factor_1","links":[{"label":"Nicholson, J Thorac Oncol 2022: the 2021 WHO classification of lung tumours, impact of advances since 2015","url":"https://doi.org/10.1016/j.jtho.2021.11.003"},{"label":"NICE NG122: lung cancer, diagnosis and staging (published 28 March 2019, last updated 8 March 2024)","url":"https://www.nice.org.uk/guidance/ng122/chapter/Diagnosis-and-staging"}],"tags":["lung"],"related":[],"cancers":["nsclc","lung-adenocarcinoma","lung-squamous-cell-carcinoma","large-cell-lung-carcinoma","lung-lcnec","lung-cancer"],"sections":[],"technologies":["histopathology-ihc","cgp"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["spread-through-air-spaces","ebus-tbna","tumour-differentiation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},"route":"/terms/ttf1-p40/","neighbours":{"cancer":[{"id":"lung-adenocarcinoma","kind":"cancer","name":"Adenocarcinoma of the lung","route":"/cancers/lung-adenocarcinoma/"},{"id":"pleuropulmonary-blastoma","kind":"cancer","name":"Childhood lung and airway tumours (pleuropulmonary blastoma, tracheobronchial tumours)","route":"/cancers/pleuropulmonary-blastoma/"},{"id":"large-cell-lung-carcinoma","kind":"cancer","name":"Large cell carcinoma of the lung","route":"/cancers/large-cell-lung-carcinoma/"},{"id":"lung-lcnec","kind":"cancer","name":"Large cell neuroendocrine carcinoma of the lung","route":"/cancers/lung-lcnec/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"lung-net","kind":"cancer","name":"Lung neuroendocrine tumours (typical and atypical carcinoid)","route":"/cancers/lung-net/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"lung-squamous-cell-carcinoma","kind":"cancer","name":"Squamous cell carcinoma of the lung","route":"/cancers/lung-squamous-cell-carcinoma/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"}],"term":[{"id":"ebus-tbna","kind":"term","name":"Endobronchial ultrasound (EBUS-TBNA)","route":"/terms/ebus-tbna/"},{"id":"spread-through-air-spaces","kind":"term","name":"Spread through air spaces (STAS)","route":"/terms/spread-through-air-spaces/"},{"id":"tumour-differentiation","kind":"term","name":"Tumour differentiation (well / moderately / poorly differentiated)","route":"/terms/tumour-differentiation/"}]}}