Table 3.
Early findings of molecular features in canine InvUC, and similarities and differences between canine and human InvUC.
| Molecular feature | Human InvUC | Canine InvUC |
|---|---|---|
| Molecular subtypes | Luminal and basal are the main subtypes. Subgroupings within these occur (13–17) | Luminal and basal are the main subtypes. Early data indicating subgroupings requires confirmation in larger studies (59) |
| P53 pathway | p53 protein (presumed mutant) is detected by immunohistochemistry (IHC). Note: wildtype p53 protein is typically degraded faster than mutant p53, and thus mutant p53 is the form that is thought to be more commonly detected by IHC (15, 60) | p63 (homolog of p53) protein (presumed wildtype) is less abundant in InvUC than in normal bladder in IHC studies (61) |
| Loss of function mutations in p53 occur in 50% of cases. Thus, the tumor suppressor pathway is inactivated (15) | P53 mutations are not well defined in canine InvUC. Enrichment has been noted in genes that negatively regulate the expression of p53 in microarray and RNA-seq analyses (59, 62) | |
| Loss of p53 function is often accompanied by loss of RB1 and amplification of MDM2 and CDKN2A (15) | RB1 expression is reduced in 5 of 8 canine InvUC cell lines (63). RB1 status has not yet been reported in clinical studies. MDM2 is overexpressed in InvUC in RNA-seq data. CDKN2B is overexpressed in RNA-seq data; CDKN2A has not been reported (59) | |
| PTEN/PI3K/AKT/mTOR pathway | Aberrant pathway activation occurs in 40% of human cases (13) | Overexpression of some genes in the pathway have been observed, but further study is needed to better characterize the pathway in dogs and to define similarities and differences between dogs and humans (59) |
| RTK/RAS pathway | FGFR3 mutations occur in 20% of cases (13) | FGFR3 mutations have not yet been defined |
| BRAF mutations are rare (13) | BRAFV600E mutations are common (~80% of cases) (64, 65) | |
| EGFR | EGFR is overexpressed in 75% of high grade tumors detected by IHC (66, 67) | EGFR is overexpressed in 73% of cases as detected by IHC (62) |
| Cox-2 | Cox-2 is overexpressed in >80% of cases as detected by IHC | Cox-2 is overexpressed in >80% of cases as detected by IHC and RNA-seq analyses (30) |