A tissue micro array analysis of Src kinase expression and activity in HNSCC

Introduction:

In a recent study analyzing the kinome of HNSCC tumors we have identified the family of Src kinases (SFK) to be frequently hyperactivated in HPV-negative HNSCC. In the present study we have analyzed the expression of Src as well as the SFK phosphorylation in an HNSCC tissue micro array (TMA).

Methods:

A tissue micro array, containing 553 HNSCC samples, was stained for Src and for phosphorylated Src kinase family members (pSFK). The immunohistological staining of the tissue samples was scored as negative, weak, moderate or strong by an established algorithm based on staining intensity (0, 1, 2, 3) and the percentage of stained tumor cells.

Results:

Strong SFK phosphorylation as a surrogate marker for high SFK activation was observed in 82.2% of the tissue samples and is therefore a common feature in HNSCC. In contrast pSFK negativity is a rare event (1.3%). Regarding Src kinase expression, 50.2% displayed strong and only 11.6% negative staining. For locally advanced HPV-negative HNSCC, a high Src staining intensity of 3 was associated with a significantly worse overall survival (logrank p = 0.0032). Regarding pSFK staining both, maximal overall scoring (strong), as well as maximal staining intensity (3) trended towards worse overall survival but did not reach significance. No trends in survival were observed for HPV-positive or early stage tumors.

Conclusions:

Our analyses identified a frequent upregulation of SFK in HNSCC and show that the extent of expression/activity may be of prognostic relevance. This indicates an important role of SFK in HNSCC tumorigenesis and points to a possible use of SFK targeting in the setting of personalized treatment strategies for HNSCC.

Publication History

Publication Date:
23 April 2019 (online)