p16, pRb, and p53 in Feline Oral Squamous Cell Carcinoma

Abstract

Feline oral squamous cell carcinoma (FOSCC) is a highly aggressive head and neck cancer in cats, but the molecular pathogenesis of this cancer is still uncertain. In this study, p16, p53, and pRb proteins were detected and quantified by immunohistochemistry in forty-three FOSCC primary tumors and three FOSCC xenografts. p16 mRNA levels were also measured in three FOSCC cell lines (SCCF1, F2, and F3), which were consistent with their p16 immunoreactivity. Feline SCCF1 cells had very high levels of p16 protein and mRNA (55-fold greater) compared to SCCF2 and F3. A partial feline p16 cDNA sequence was amplified and sequenced. The average age of cats with FOSCC with high p16 immunoreactivity was significantly lower than the average age in the low p16 group. Eighteen of 43 (42%) FOSCCs had low p16 intensity, while 6/43 (14%) had high p16 immunoreactivity. Feline papillomavirus L1 (major capsid) DNA was not detected in the SCC cell lines or the FOSCCs with high p16 immunostaining. Five of 6 (83%) of the high p16 FOSCC had low p53, but only 1/6 (17%) had low pRb immunoreactivity. In summary, the staining pattern of p16, p53, and pRb in FOSCC was different from human head and neck squamous cell carcinoma and feline cutaneous squamous cell carcinoma. The majority of FOSCCs have low p16 immunostaining intensity, therefore, inactivation of CDKN2A is suspected to play a role in the pathogenesis of FOSCC. A subset of FOSCCs had increased p16 protein, which supports an alternate pathogenesis of cancer in these cats.

A virome sequencing approach to feline oral squamous cell carcinoma to evaluate viral causative factors

“…FcaPV was only detected in 1 of 20 FOSCC samples. These results are consistent with all published literature that includes > 1 FOSCC patient, where PV infection was detected in only 0-6.9% of patients (Munday and French, 2015;Munday et al, 2019Munday et al, , 2009Munday et al, 2011b;O'Neill et al, 2011;Supsavhad et al, 2016;Yamashita-Kawanishi et al, 2018). It is possible that PV was not detected but causes FOSCC via a 'hit and run' mechanism, where E6 and E7 contribute to tumor initiation, the virus is lost in overt neoplasms, and it is not required to maintain the transformed phenotype.…”

“…Increased expression of p16, E6 and E7 and decreased expression of pRb and p53 would be expected in high-risk PV induced lesions. Decreased p53 and pRB expression and increased p16 expression was found in only 2.3% of FOSCC samples and all samples with high p16 expression were negative for PV (Supsavhad et al, 2016). Increased p16 expression has been identified as a positive prognostic factor in FOSCC but has only been seen in a minority of samples, 6.7% to 19%, and has not been associated with PV infection (Munday et al, 2019(Munday et al, , 2011b.…”

Prevalence of p53 dysregulations in feline oral squamous cell carcinoma and non-neoplastic oral mucosa

“…Serial sections of FOSCC, eosinophilic granuloma, chronic gingivostomatitis and normal oral mucosa were immunolabeled for p53 using a commercial mouse monoclonal antibody (Pab 240 clone, BD Biosciences, San Jose, California, USA) with validated reactivity in feline tissues. [20, 22, 28]…”

“…In FOSCC, the IHC expression of p53 has been reported in 24% to 65% of cases, [20–22] and an association between p53 expression and exposure to household environmental tobacco smoke (ETS) was hypothesized. [21] Although an anecdotal report exists of a TP53 mutation in a FOSCC, [23] no study has systematically evaluated the presence of TP53 mutations in these tumors, nor their association with IHC protein expression.…”

CD147 and Cyclooxygenase Expression in Feline Oral Squamous Cell Carcinoma

“…The importance of HPV infection in human OSCC has inspired researchers to look for feline papillomaviruses in feline OSCC. Although the feline oral cavity can be infected with papillomavirus [ 11 ], a link between papillomavirus infection and feline OSCC has yet to be demonstrated [ 12 ].…”