Large-scale comparative analyses of immunomarkers for diagnostic subtyping of non-small-cell lung cancer biopsies.

AIMS

Patient stratification according to histological subtype is important for non-small-cell lung cancer (NSCLC) therapy. For specimens with uncertain histomorphology, rational and material-saving algorithms for specific and sensitive immunotyping need to be established.

METHODS AND RESULTS

One thousand one hundred and forty-five NSCLCs were immunohistochemically investigated for the expression of cytokeratin 5/6 (CK5/6), CK7, thyroid transcription factor-1 (TTF-1), p63, napsin-A, and desmocollin-3. Overall, napsin-A and desmocollin-3 were the most specific markers (specificity of each, 99%), and CK7 and CK5/6 the most sensitive markers (sensitivity, 96% and 94%) for adenocarcinomatous and squamous differentiation, respectively. However, for NSCLC not otherwise specified (NOS) cases, TTF-1, p63, CK5/6 and CK7 were found to be the most reliable markers. On the basis of morphology alone, approximately two-thirds of all NSCLCs could be reliably diagnosed in biopsy specimens. Immunohistochemistry further reduced the NOS fraction to 10%.

CONCLUSIONS

When morphology alone is not reliable, the use of selected markers and marker panels is highly sensitive and specific, and allows reliable distinction between squamous cell carcinoma and adenocarcinoma. Considering the impact of typing for the selection of molecular testing and treatment response, one must be aware of immunomarker expression patterns in NSCLC and their diagnostic value, in order to optimize typing and thereby maximize patient benefit from chemotherapy.