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Review
. 2011 Aug;108(31-32):525-31.
doi: 10.3238/arztebl.2011.0525. Epub 2011 Aug 8.

The morphological and molecular diagnosis of lung cancer

Iver Petersen  1
Affiliations
Review

The morphological and molecular diagnosis of lung cancer

Iver Petersen. Dtsch Arztebl Int. 2011 Aug.

Abstract

Background: In Germany, lung cancer causes more deaths than any other malignant disease. Its main etiology is smoking, but other risk factors need to be considered as well. The morphological, molecular and biological phenotype is complex and should no longer be just categorized as either small-cell or non-small cell lung cancer.

Methods: This review article is based on the authors' longstanding involvement in the scientific investigation and diagnostic evaluation of lung cancer, including contributions to the current WHO classification and collaboration in the new interdisciplinary classification of adenocarcinoma. The relevant literature was selectively reviewed.

Results: Lung cancer is morphologically classified into four main subtypes-small-cell carcinoma, squamous-cell carcinoma, adenocarcinoma, and large-cell carcinoma. Genetic and molecular analyses have revealed distinct differences within subtypes; in particular, adenocarcinomas can be further subdivided. Complex techniques of genomic analysis are now available, but clinicopathological data are still the most important determinants of prognosis and are clearly better for this purpose than molecular classification alone. Nonetheless, the assessment of specific molecular markers is becoming increasingly important.

Conclusion: The morphological and molecular classification of lung cancer is undergoing a re-evaluation which will lead to more accurate assessment of individual prognoses and to improved prediction of the response to specific treatment regimens.

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Figures

Figure 1
Figure 1
Examples of the histomorphology of the four main types of lung cancer: a) squamous cell carcinoma (p63, CK5/6); b) adenocarcinoma (TTF1, CK7); c) large cell carcinoma. These three main types constitute the group of non–small cell lung cancers. d) Small cell carcinoma (synaptophysin, chromogranin, CD56/NCAM). Typical immunochemical marker proteins of each individual entity are listed in parentheses. These may, however, be lacking or expressed in other entities, and the immunophenotype should therefore always be interpreted in the morphological context
Figure 2
Figure 2
Classification of lung cancer by means of hierarchical clustering (adapted from [12]). The columns correspond to individual tumor specimens, the rows to individual genes, which are grouped according to their similarity by means of cluster analysis. The analysis identified the four main types of lung cancer and the three subtypes of adenocarcinoma. Characteristic genes that are responsible for the grouping of the tumor types are listed to the right. In case of green coloring the respective genes of the tumor specimens were subject to reduced expression at the mRNA level, red signifies overexpression.
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