Lung Cancer Immunohistochemistry Markers
Lung cancer is the second most common cause of cancer deaths in the U.S. Lung cancers exist as three subtypes: non-small cell lung cancers (NSCLC),
which are comprised of the adenocarcinoma and squamous cell carcinoma subtypes that together account for 75% of cases, and small cell lung cancers (neuroendocrine origin)
which account for the remainder.
The availability of targeted therapies makes it essential to correctly subtype NSCLCs: IHC markers such as
NKX2-1 / TTF-1
, Napsin A
and surfactant A (adenocarcinoma)
(squamous cell carcinoma) can be used to identify the subtype in cases where the morphology is unclear, or with biopsies where there is
insufficient material to make the diagnosis (Noh, 2012; Gurda, 2015). Small cell lung cancers can be identified with markers such as
, and NKX2-1 / TTF-1
Although platinum-based chemotherapy has been the standard treatment for metastatic NSCLC, lung cancers with mutations associated with epidermal growth factor receptor
) and anaplastic lymphoma kinase (ALK) may respond to specific kinase inhibitors
, so there is a
need to identify the subset that show these mutations (Cooper, 2011; Malhotra, 2017; Kumar, Curr Probl Cancer 2017 Mar - Apr;41(2):111-124). Furthermore...
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Aryl hydrocarbon receptor (AHR) is a transcription factor involved in xenobiotic metabolism and autophagy and it is expressed in many tissues including lung. In cancer, AHR is involved in migration and proliferation, and is upregulated in pancreatic, liver, head and neck, lung, thyroid and gastrointestinal tumors. AHR appears to function in both tumor suppression and tumorigenesis depending on the cell type and tissue (Tsai, 2017; Safe, 2013). In the lung, AHR expression is correlated with smoking-induced tumors, where carcinogens such as BaP directly bind to AHR and induce xenobiotic metabolism. Activation of AHR leads to upregulation of CYP1A1 and other cytochrome P450 enzymes, which are responsible for metabolizing carcinogens but can sometimes create a more damaging substance in error (Tsay, 2013). Higher expression of AHR in lung carcinomas is associated with a worse prognosis, particularly in tumors with mutant EGFR. In these tumors, the activation of AHR induces oncogenic Src expression and functional proliferative signaling (PI3K/Akt), resulting in resistance to tyrosine kinase inhibitors that target EGFR (Ye, 2017).
AHR is expected to have nuclear and cytoplasmic staining.