Accurate characterisation of gastrointestinal stromal tumours (GIST) is important
for prognosis and the choice of targeted therapies. Histologically the diagnosis relies
on positive immunostaining of tumours for KIT (CD117) and DOG1. Here we report that
GISTs also abundantly express the type 3 Sarco/Endoplasmic Reticulum Calcium ATPase
(SERCA3). SERCA enzymes transport calcium ions from the cytosol into the endoplasmic
reticulum and play an important role in regulating the intensity and the periodicity
of calcium-induced cell activation. GISTs from various localisations, histological
and molecular subtypes or risk categories were intensely immunopositive for SERCA3
with the exception of PDGFRA-mutated cases where expression was high or moderate.
Strong SERCA3 expression was observed also in normal and hyperplastic interstitial
cells of Cajal. Decreased SERCA3 expression in GIST was exceptionally observed in
a zonal pattern, where CD117 staining was similarly decreased, reflecting clonal heterogeneity.
In contrast to GIST, SERCA3 immunostaining of spindle cell tumours and other gastrointestinal
tumours resembling GIST was negative or weak. In conclusion, SERCA3 immunohistochemistry
may be useful for the diagnosis of GIST with high confidence, when used as a third
marker in parallel with KIT and DOG1. Moreover, SERCA3 immunopositivity may be particularly
helpful in cases with negative or weak KIT or DOG1 staining, a situation that may
be encountered de novo, or during the spontaneous or therapy-induced clonal evolution
of GIST.
