Characterisation of DOG-1 Expression in Salivary Gland Tumours and Comparison with Myoepithelial Markers

Abstract

DOG1 is an established diagnostic marker for gastrointestinal stromal tumours (GIST), but has been reported in salivary gland tumours (SGT) as an acinar and intercalated duct marker. However, its specificity and distribution is not well established. The aim of this study was to evaluate the diagnostic utility of DOG-1 expression in SGT in addition to comparing it with myoepithelial markers. Normal salivary tissue and SGT (n = 184) were examined for expression of DOG1 and a range of myoepithelial markers. SGT included: acinic cell carcinoma (ACC, n = 15), secretory carcinoma (SC, n = 9), pleomorphic adenoma (PA, n = 49), carcinoma ex-PA (Ca ex-PA, n = 11), adenoid cystic carcinoma (AdCC, n = 20), polymorphous adenocarcinoma (PAC, n = 6), myoepithelioma (n = 6), myoepithelial carcinoma (MC, n = 2), basal cell adenoma (BCA, n = 14), canalicular adenoma (CA, n = 19), mucoepidermoid carcinoma (MEC, n = 11), oncocytoma (n = 2), adenocarcinoma NOS (AdNOS, n = 4), basal cell adenocarcinoma (BCAC, n = 2), salivary duct carcinoma (SDC, n = 3) and papillary cystadenocarcinoma (PCAC, n = 1). Normal acini and ACC (14/15) showed strong luminal DOG1 staining; SC were largely negative with only focal expression in 3/9 cases. Luminal staining was seen in PA (14/49), PAC (4/6), Ca ex-PA (4/11) and AdCC (6/20). 8/11 MEC showed luminal and/or mucous cell staining. No staining was seen in myoepithelioma, MC, CA, adNOS and BCAC. BCA showed strong staining of myoepithelial cells in some cases (5/14). Variable myoepithelial DOG1 staining was seen in PA, Ca ex PA, BCA, SDC and PCAC which was not as consistent as myoepithelial markers such as calponin, p63 and αSMA. Absence of DOG1 can differentiate ACC from SC, but staining is variable in PA, PLGA and Ca ex-PA. Myoepithelial staining in some tumours but not in normal gland suggests a wider distribution in SGT than originally envisaged.

Keywords: Acinic cell carcinoma; DOG-1; Luminal; Myoepithelial; Salivary gland tumours; Secretory carcinoma.

Fig. 1

Representative photomicrographs showing DOG-1 staining pattern in a normal gland; b acinic cell CA; c secretory carcinoma—negative; d secretory carcinoma—focal positive, e pleomorphic adenoma; f adenoid cystic CA; g mucoepidermoid carcinoma; h basal cell adenoma; i carcinoma in pleomorphic adenoma; j papillary cystadenocarcinoma. g Solid arrow—mucous cells, dotted arrow—intermediate cells, double arrow—luminal spaces with DOG1 positivity

Fig. 2

Calponin staining in a pleomorphic adenoma, b Ca ex-pleomorphic adenoma, c myoepithelioma and d PAC. Staining was predominantly seen in myoepithelial cells surrounding the ductal areas in (a, b). In c, scattered staining in spindle cells was seen throughout. PAC were negative except with one case showing focal staining. d Calponin staining highlighting the abluminal/myoepithelial cells Cribriform AdCC and e tubular AdCC (original magnification ×20)

Fig. 3

CK14 staining in salivary gland tumours a in normal tissue CK14 staining was mainly seen as a cytoplasmic staining of myoepithelial cells surrounding acini and in some basal cell in ducts, b CK14 in ACC was variable with one case showing diffuse abluminal staining, c CK14 in one SC with diffuse cytoplasmic staining of abluminal cells, d CK14 staining in PA was predominantly seen in the cytoplasm of most tumour cells, but plasmacytoid cells were negative, e CK14 expression in CA ex-PA was mainly seen in the cytoplasm of the abluminal type cells, f CK14 staining in myoepithelioma was variably positive in the cytoplasm of the neoplastic myoepithelial cells, mainly spindle cells, g CK14 staining in MC was focal with cytoplasmic staining of scattered tumour cells, i CK14 staining in AdCC (cribriform variant) and j PAC—diffuse staining was seen throughout the tumour (original magnification ×20)

Fig. 4

S100 staining in salivary gland tumours. a Nuclear and cytoplasmic staining in myoepithelial cells in PA whereas luminal cells were largely negative, b S100 expression in Ca ex-PA with diffuse staining in the cytoplasm of luminal, abluminal and scattered stromal cells, c myoepithelioma showing diffuse cytoplasmic S100 staining in the neoplastic spindle cells, d S100 staining in MC with strong cytoplasmic staining in the plasmacytoid cells, e PAC showed diffuse staining in almost all the tumour cells (original magnification ×20)