Pattern of desmogleins 1 and 3 co-expression in human tumours: a TMA study on 16,100 tumours

Abstract

Desmogleins are glycoproteins of the desmosomes of squamous epithelia. To understand the roles of desmogleins (Dsgs) 1 and 3 in cancer, tissue microarrays containing 16,100 samples from 138 different tumour types were analysed by IHC. Dsg1 and Dsg3 staining was detectable in 39 (28%) and 49 (36%) of 138 tumour categories. Four of 12 squamous cell cancer types showed ≥90% positivity for Dsg1 and/or Dsg3, and another 7 SQCC types showed 80–89% positivity. Dsg1 and/or Dsg3 positivity was also found in basal cell carcinomas (52% Dsg1/3 positive), Warthin tumours (39%), basal cell adenomas (30%), teratomas (26%) and muscle invasive urothelial carcinomas (22%). High Dsg1 expression was linked to high grade, loss of ER/PR positivity (p<0.0001 each) and reduced survival (p=0.0426) in breast cancer. High Dsg3 expression was linked to invasive growth in urothelial carcinoma (p<0.0001) and to high pT (p=0.0102), pN+ (p=0.0162), blood vessel infiltration (p=0.0189) and lymph vessel infiltration (p=0.0151) in colorectal cancer. Reduced expression of Dsg1/3 was linked to high grade in 599 squamous cell carcinomas from 12 different sites (p<0.0001 each). In summary, loss of Dsg1/3 goes along with dedifferentiation in squamous cell carcinomas, while upregulation is linked to adverse tumour features in non-squamous cancers.