PDGFRs expression in dogs affected by malignant oral melanomas: correlation with prognosis

Canine malignant melanoma (CMM) is the most common canine oral tumour, and up to 70-75% of dogs in stage II-III die within 1 year after surgery. The purpose of this study was to evaluate the expression of platelet-derived growth factors receptors (PDGFR)-α and -β in stage II and III CMMs and to correlate it with prognosis. PDGFRs expression was evaluated by immunohistochemistry on 48 cases of formalin-fixed CMM samples and correlated with clinical-pathological findings and outcome after surgery. PDGFRs co-expression was observed in 37.5% of cases. Positivity for PDGFR-α and -β receptor was present in 54.2 and 47.9% of cases, respectively. Ki67 values >19.5% were ascertained in 66.7% of cases. Statistical analysis showed that PDGFRs co-expression and Ki67 values > 19.5% were both associated with worse prognosis. PDGFRs expression suggests a role in the pathogenesis and progression of CMM, and α and β co-expression appears to be associated to worse prognosi

Activation of mammalian target of rapamycin (mTOR) in triple negative feline mammary carcinomas

BACKGROUND: Triple negative breast cancer (TNBC) in humans is defined by the absence of oestrogen receptor (ER), progesterone receptor (PR) and HER2 overexpression. Mammalian target of rapamycin (mTOR) is overexpressed in TNBC and it represents a potential target for the treatment of this aggressive tumour. Feline mammary carcinoma (FMC) is considered to be a model for hormone-independent human breast cancer. This study investigated mTOR and p-mTOR expression in FMC in relation to triple negative (TN) phenotype. RESULTS: The expression of mTOR, p-mTOR, ERα, PR and HER2 was evaluated in 58 FMCs by immunohistochemistry and in six FMC cell lines by Western blot analysis. 53.5% of FMC analyzed were ER, PR, HER2 negative (TN-FMC) while 56.9% and 55.2% of cases expressed mTOR and p-mTOR respectively. In this study we found that m-TOR and p-mTOR were more frequently detected in TN-FMC and in HER2 negative samples. CONCLUSIONS: In this study, we demonstrate that there is also a FMC subset defined as TN FMC, which is characterised by a statistically significant association with m-TOR and p-mTOR expression as demonstrated in human breast cancer

Prolongation of survival of dogs with oral malignant melanoma treated by en bloc surgical resection and adjuvant CSPG4-antigen electrovaccination

Reported post-surgery 1-year survival rate for oral canine malignant melanoma (cMM) is around 30%; novel treatments are needed as the role of adjuvant chemotherapy is unclear. This prospective study regards adjuvant electrovaccination with human-CSPG4-encoded plasmid in 23 dogs with resected II/III-staged CSPG4-positive oral cMM compared with 19 dogs with resected only II/III-staged CSPG4-positive oral cMM. Vaccination resulted in 6/12/18/24-month survival rate of respectively 95.6/73.9/47.8/30.4% (MST 684 days, range 78-1694, 8/23 dogs alive) and 6/12/18/24-month DFI rate of respectively 82.6/47.8/26.1/17.4% (DFI 477 days, range 50-1694). Non-vaccinated dogs showed 6/12/18/24-month survival rate of respectively 63.2/26.3/15.8/5.3% (MST 200 days, range 75-1507, 1/19 dogs alive) and 6/12/18/24-month DFI rate of respectively 52.6/26.3/10.5/5.3% (DFI 180 days, range 38-1250). Overall survival and DFI of vaccinated dogs was longer in those <20 Kg. In vaccinated and non-vaccinated dogs local recurrence rate was respectively 34.8% and 42% while lung metastatic rate was respectively 39% and 79%