Aberrantly expressed GFRα-1/RET in patients with lacrimal adenoid cystic carcinoma is associated with high recurrence risk:a retrospective study of 51 LACC cases

Objective:Because of the poor prognosis of lacrimal adenoid cystic carcinoma(LACC),we aimed to investigate the effects of perineural invasion(PNI)and consequent aberrations in GDNF/GFRα-1/RET protein expression on LACC recurrence.Methods:Clinicopathological data for 51 histologically confirmed patients with LACC enrolled between 2001 and 2017 were retrospectively analyzed.Hematoxylin and eosin staining was applied to assess PNI.Tissue-based immunohistochemistry(IHC)detection of GDNF,GFRα-1,and RET proteins was performed on LACC formalin-fixed,paraffin-embedded specimens.We generated semi-quantitative data of the IHC results and compared them with the clinicopathological data for the 51 patients.Results:Of the 51 patients,19(37.3%)were PNI positive.Recurrence was more common for LACC with than without PNI(73.7%vs.37.5%,P=0.01).GDNF,GFRα-1,and RET proteins were expressed in 62.7%,62.7%,and 54.9%of the 51 patients with LACC,respectively.The expression of all 3 proteins was more common in patients with than without PNI.In agreement with previous findings,PNI-associated GFRα-1 and RET positivity,as detected by IHC,remained significantly associated with recurrence,whereas GDNF expression,as detected by IHC,was not correlated with LACC recurrence.Specifically,patients with concurrent GFRα-1 and RET expression may have a high risk of PNI(89.5%positivity rate)and recurrence(84.2%positivity rate).Conclusions:PNI may contribute to LACC recurrence.The concurrent expression of GFRα-1 and RET proteins,as detected by IHC,may potentially be associated with LACC PNI and recurrence.