Increased p16CDKN2A, but not p53, immunostaining is predictive of longer survival time in cats with oral squamous cell carcinomas

Munday, John S.; He, Yanyu; Klobukowska, Hanna J.

doi:10.1016/j.tvjl.2019.04.007

Cited by 14 publications

(32 citation statements)

References 32 publications

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“…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.…”

Section: Discussionsupporting

confidence: 91%

“…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. High-risk PVs encode an E6 protein that binds to p53 sufficiently to induce ubiquitin proteolysis (Faraji et al, 2017).…”

Section: Discussionmentioning

confidence: 95%

“…None of the PV-positive FOSCC lesions from previous studies were classified as oropharyngeal ( Supplementary Table 2). To the author's knowledge PV status of oropharyngeal FOSCC has been evaluated in only 15 cats to date (Munday and French, 2015;Munday et al, 2019Munday et al, , 2009Munday et al, 2011b;O'Neill et al, 2011). Tonsillar FOSCC lesions have been associated with a better prognosis, than FOSCC lesions located in the oral cavity, when treated with an accelerated radiation therapy and carboplatin protocol (Fidel et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

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

Chu

Wylie

et al. 2020

Veterinary Microbiology

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Feline oral squamous cell carcinoma (FOSCC) may be the best naturally-occurring model of human head and neck squamous cell carcinoma (HNSCC). HNSCC can be broadly divided into human papillomavirus (HPV)negative cancers and HPV-positive cancers where HPV is the causative agent. Previous studies in FOSCC have used both species-specific and species-nonspecific PCR primers that may be insensitive to the detection of PVs and other viruses that may be divergent from known sequences. ViroCap is a targeted capture and next generation sequencing tool that was designed to identify all known vertebrate DNA and RNA viruses. In this study we used a metagenomic approach using ViroCap for DNA viruses in 20 FOSCC, 9 normal feline oral mucosal, and 8 suspected PV positive control samples. We tested the hypothesis that viruses would be enriched in FOSCC compared to normal oral mucosa. The virome of the FOSCC and normal feline oral mucosa consisted of feline foamy virus in 7/20 and 2/9 (35% and 22%), feline torque teno virus in 2/20 and 0/9 (10% and 0%), alphaherpesvirus in 2/10 and 0/9 (10% and 0%), FIV (0% and 22%), Epstein-Barr virus in 1/20 and 0/9 (5% and 0%) and feline papillomavirus in 1/20 and 0/9 samples (5% and 0% respectively). Felis catus papillomavirus-3 was found in 1 of 20 FOSCC samples. A virus was not associated consistently with FOSCC. If PVs have a role in FOSCC it is at most a supplementary or uncommon role. FOSCC appears most closely related to HPV-negative HNSCC. Future research on FOSCC should focus on identifying genetic and environmental causes. (S. Chu). Veterinary Microbiology 240 (2020) 108491 0378-1135/ Published by Elsevier B.V.T

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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

Chu

Wylie

et al. 2020

Veterinary Microbiology

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“…In these works, different sets of consensus oligos were employed, since they are able to amplify conserved regions of mucosal and cutaneous PVs, including FcaPV-2 from feline skin SCC. [11][12][13][14][15][16] However, Munday et al detected PV DNA in 1/20 FOSCC (mostly similar to HPV-76) vs 0/20 non-neoplastic oral lesions, and in 0/30 FOSCC by the use of FAP59/64 and MY09/11 primers in two different reports. 12,13 By similar approach, O'Neill et al found two PVs sequences in 2/30 FOSCC, however, one was not sequenced and the other was identified as HPV-38.…”

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confidence: 99%

Detection of Felis catus papillomavirus type‐2 DNA and viral gene expression suggest active infection in feline oral squamous cell carcinoma

Altamura

Cardeti

Cersini

et al. 2020

Vet Comparative Oncology

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Papillomavirus (PV) infection is associated with development of epithelial cancer in different species, including domestic cat (Felis catus). Felis catus PV type-2 (FcaPV-2) is considered the causative agent of a proportion of feline cutaneous squamous cell carcinoma (SCC), through the transforming properties of its E6 and E7 oncogenes. However, the possible role of FcaPVs in the aetiology of feline oral SCC (FOSCC) is still unclear. The aim of this study was to assess the presence and gene expression of FcaPV-2 in FOSCC samples. We detected FcaPV-2 DNA in 10/32 (31%) of the analysed FOSCC by the use of PCR methods. Importantly, viral mRNA was detected by RT-PCR in 7/10 (70%) of DNA positive samples. In particular, FcaPV-2 L1, E2 and E6E7 genes were found to be expressed in 5/10 (50%), 3/10 (33%) and 5/10 (50%) samples, respectively. Viral DNA was also detected in non neoplastic oral ulcerative lesions (ULs) (4/11, 36%); qPCR suggested a difference in viral load between ULs and FOSCCs, particularly in those expressing E6E7, although it was not statistically significant. These data suggest, but do not definively prove, a possible role of FcaPV-2 in the development of a proportion of FOSCC. Moreover, L1 and E2 gene expression results indicate that FcaPV-2 infection associated with these tumours may possibly be productive.

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“…Moreover, another study showed that increased CDKN2A immunostaining indicated increased survival time in cats with oral squamous cell carcinomas [12]. In addition, Ganjoo's study noted that CDKN2A deletion was associated with poor prognosis in histological subtypes of sarcoma [13].…”

Section: Introductionmentioning

confidence: 99%

Upregulated CDKN2A expression may be an independent protective factor in Luminal-like breast cancer

Qiu¹,

Lu²,

Wu³

2020

Preprint

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Background Previous studies revealed that CDKN2A (cyclin-dependent kinase inhibitor 2A) functioned as a tumour suppressor in various types of malignant tumours. The aim of the study was to clarify the value of CDKN2A expression in the prognosis of breast cancer. Method Using the Cancer Genome Atlas (TCGA) database, we compared CDKN2A mRNA levels between breast cancer tissues and normal tissues and analyzed the relationship between clinical features and CDKN2A expression with the Wilcox test and the Kruskal-Wallis test. Kaplan-Meier and Cox analyses were performed to determine the correlation between CDKN2A expression and breast cancer prognosis. Gene set enrichment analysis (GSEA) was performed using the TCGA data set. Results We first found that CDKN2A expression was markedly higher in breast cancer tissues than in normal tissues using the TCGA database (P=0.000). In addition, CDKN2A mRNA expression in breast cancer was positively correlated with age (P=0.018), histological types (P=0.028), ER status (P=0.000), PR status (P=0.000) and molecular subtypes (P=0.000). Kaplan-Meier analysis showed that increased CDKN2A expression was associated with increased survival time in breast cancer patients (P=0.000), especially in Luminal-like subtype. Univariate and multivariate Cox analyses indicated that CDKN2A expression was an independent prognostic biomarker for breast cancer (P=0.037). GSEA suggested that pathways involving cell adhesion molecules (CAMs), cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity were differentially enriched in the CDKN2A-high expression group. Conclusion Our research demonstrated that high CDKN2A mRNA expression was an independent protective factor for improved prognosis in Luminal-like breast cancer. Additionally, the signaling pathways related to CAMs, cytokine-receptor interactions, cytosolic DNA sensing, the cell cycle, and killer cell-mediated cytotoxicity regulated by CDKN2A mRNA expression should be further studied.

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Increased p16CDKN2A, but not p53, immunostaining is predictive of longer survival time in cats with oral squamous cell carcinomas

Cited by 14 publications

References 32 publications

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

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

Detection of Felis catus papillomavirus type‐2 DNA and viral gene expression suggest active infection in feline oral squamous cell carcinoma

Upregulated CDKN2A expression may be an independent protective factor in Luminal-like breast cancer

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