Comparative mutational profiling in the assessment of lung lesions: should it be the standard of care?

Abstract

Background: Discerning primary versus metastatic lung lesions is problematic. Comparative mutational profiling (CMP) involves genetic and point mutation analysis of lesions to facilitate this. We sought to review our experience in cases of two lung lesions or head and neck cancer and lung lesions to determine whether a significantly clinical problem existed, what standard processes were in place to address it, and whether a new diagnostic standard was required.

Methods: Between January 1, 2007, and October 31, 2008, CMP was used in 24 cases of two lung lesions or a head and neck cancer and lung lesion. Routine hematoxylin and eosin stain examination and immunohistochemistry were performed as appropriate. The CMP involved DNA sequencing for specific oncogene point mutations and a panel of allelic imbalance markers. Metastatic cancer required demonstration of concordant mutations affecting the same allele copy in different cancer deposits.

Results: The patient mean age was 62 years; there were 13 men and 11 women. The cases involved two lung lesions (n = 13) or a head and neck cancer and a lung lesion (n = 11). Standard pathology examination was unable to discriminate the lesions, and they were subsequently differentiated by CMP. Fifteen discordant CMP results were interpreted as independent primaries; 9 cases were concordant, consistent with metastatic disease.

Conclusions: Discerning primary versus metastatic disease when dealing with lung lesions is a clinically significant problem. Comparative mutational profiling was found to be useful and reliable to assess the relatedness of multiple cancer lesions when routine pathology assessment was unable to.