The neurotrophic
tyrosine kinase receptor TrkA (NTRK1) and its
ligand nerve growth factor (
NGF) are emerging promoters of
tumor progression. In
lung cancer, drugs targeting TrkA are in clinical trials, but the clinicopathological significance of TrkA and
NGF, as well as that of the precursor proNGF, the
neurotrophin co-receptor p75NTR and the proneurotrophin co-receptor
sortilin, remains unclear. In the present study, analysis of these
proteins was conducted by immunohistochemistry and digital quantification in a series of 204
lung cancers of different histological subtypes versus 121 normal lung tissues. TrkA immunoreactivity was increased in
squamous cell carcinoma compared with benign and other malignant
lung cancer histological subtypes (p < 0.0001).
NGF and proNGF were also increased in
squamous cell carcinoma, as well as in
adenocarcinoma (p < 0.0001). In contrast, p75NTR was increased across all
lung cancer histological subtypes compared to normal lung (p < 0.0001).
Sortilin was higher in
adenocarcinoma and
small cell carcinoma (p < 0.0001). Nerves in the tumor microenvironment were negative for TrkA,
NGF, proNGF, p75NTR and
sortilin. In conclusion, these data suggest a preferential therapeutic value of targeting the
NGF-TrkA axis in
squamous cell carcinomas of the lung.