Immunohistochemistry in lung cancer diagnostics and research

Adenocarcinoma diagnostiska markörer.jpg
NKX2-1 (top) and NAPSA (bottom) show high protein expression in lung adenocarcinoma and no expression in lung squamous cell carcinoma.
Squamous carcinoma diagnostiska markörer.jpg
KRT5 (top) and TP53 (bottom) show no protein expression in lung adenocarcinoma and high expression in lung squamous cell carcinoma.
S100A10 is expressed in lung cancer at variable levels. Left: adenocarcinoma; right: squamous cell carcinoma.

Previous news articles featured the history and technology behind two powerful tools for visualizing proteins in tissues: immunohistochemistry and microscopy. These tools are applied to investigate and answer a wide range of questions, both in healthcare and research. This article focuses on two applications related to lung cancer: diagnostics in clinical pathology and discovery of genes associated with prognosis.

In clinical pathology, immunohistochemistry is applied to identify and characterize cancer in patients. Correct diagnosis has profound effects on patients, including receiving suitable treatment. There are a large number of established diagnostic markers and exactly which of these proteins are examined in any given patient sample depends on the suspected cancer type.

A part of lung cancer pathology is differentiation between the two major subtypes of non-small cell carcinoma: adenocarcinoma (LUAD) and squamous cell carcinoma (LSCC). Diagnosis with immunohistochemistry is based on that proteins NKX2-1 (TTF1) and NAPSA (Napsin A) are expressed by LUAD and not LSCC, while TP53 (p40) and KRT5 (cytokeratin 5) are expressed by LSCC and not LUAD.

NKX2-1 is a nuclear protein that plays an important role in transcription. NAPSA is a protease with a suggested role in post-translation modification of a surfactant protein essential for normal lung function. KRT5 is a component of stratified epithelia and expressed in the basal layer of epidermis. P40, also known as delta-Np63, is an isoform of the tumor suppressor protein p53 encoded by the gene TP53.

One question that researchers investigate is how expression of genes may be related to survival outcome in cancer patients. An example of this is a study by Uhlén et al, which provides the basis for the Pathology Atlas. By comparing global gene expression and overall survival in over 8,000 patients, they found that over two thirds of protein-coding genes are associated with cancer prognosis. Immunohistochemical staining of an independent cohort of lung cancer patients contributed to further validation of eight different prognostic genes in lung cancer (CADM1, ANLN, TACC3, SLC2A1, MKI67, S100A16, S100A10, ERO1A). Results showed that not only gene expression, but also corresponding protein expression was associated with prognosis.

S100A10 is one of the proteins whose prognostic value was confirmed. It is a member of the S100 calcium binding family located in the cell membrane. Immunohistochemical analysis showed widespread expression at variable levels and high expression of S100A10 was found to be associated with poor survival outcome.

Would you like to know more about prognostic genes in lung cancer? Read the full publication by Uhlén et al.

Lung cancer diagnostics is described in more detail in the report WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart 2015.

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