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Relationship between CK19 expression, deregulation of normal keratinocyte differentiation pattern and high risk-human papilloma virus infection in oral and oropharyngeal squamous cell carcinoma

Overview of attention for article published in Infectious Agents and Cancer, December 2015
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Title
Relationship between CK19 expression, deregulation of normal keratinocyte differentiation pattern and high risk-human papilloma virus infection in oral and oropharyngeal squamous cell carcinoma
Published in
Infectious Agents and Cancer, December 2015
DOI 10.1186/s13027-015-0041-x
Pubmed ID
Authors

Angela Santoro, Giuseppe Pannone, Rossella Ninivaggi, Massimo Petruzzi, Andrea Santarelli, Giuseppe Maria Russo, Silvia Lepore, Michele Pietrafesa, Ilaria Laurenzana, Rosalia Leonardi, Paolo Bucci, Maria Iole Natalicchio, Alberta Lucchese, Silvana Papagerakis, Pantaleo Bufo

Abstract

Simple epithelial keratins appear early during embryonic development and are expressed in non-stratified, ductal and pseudo-stratified epithelial tissues. CK19, the lowest molecular weight keratin, is also expressed in basal layer of squamous epithelia of mucosal surfaces. Previous studies have shown that High Risk-Human Papilloma Virus (HR-HPV) epithelial infection induces cell immortalization via E6 and E7 viral proteins and this, in turn, impairs cytokeratin expression in cancerous cells lines derived from uterine cervix. Here, we demonstrate the possible relationship between HR-HPV(+) oral/oropharyngeal cancer and the high levels of CK19 expression. We analyzed 38 cases of Oral Squamous Cell Carcinomas/ Oro-Pharyngeal Squamous Cell Carcinomas (OSCCs/OPSCCs) by Immunohistochemistry (IHC) using specific antibody (Ab) detecting CK19, by In Situ Hybridization (ISH) and Polymerase Chain Reaction (PCR) based methods in order to define the HPV infectious status. We also evaluated the variation of CK19 expression in UPCI-SCC-131 (HPV(-)) and UPCI-SCC-154 (HPV(+)) cell lines by immunocytochemistry (ICC) and flow cytometry. CK19 OSCC/OPSCC score has been identified multiplying percentage of cancer expressing cells to staining intensity. CK19 expression score in OSCCs/OPSCCs was very different between HPV(+) (mean: 288.0 ± 24.3) and HPV(-) cancers (mean: 66.2 ± 96.9). This difference was statistically significant (p < 0.001) with a strong evidence of correlation (p < 0.001; Spearman's R: +0.72). ROC curve analysis was performed on CK19 expression index related to HPV positivity. Heterogeneous areas of immunoreactivity varying in percentage value, intensity and/or localization were observed in normal epithelium, both perilesional and distant from the tumor with important differences between HR-HPV(+) and HR-HPV(-) carcinomas. By ICC and flow cytometry, the two analyzed cell lines were both CK19 positive but showed a different level of expression, in particular it should be noted that the UPCI-SCC-154 (HPV(+)) cell line had a higher expression than UPCI-SCC-131 (HPV(-)). In this study we demonstrated, for the first time, strong association between CK19 up-regulation and HR-HPV(+) OSCCs/OPSCCs. This test has a good accuracy. We identified ROC curve with a cut-off > 195 for HR-HPV positive results (Sensitivity: 92.3 %; Specificity: 89.3 %). Furthermore, in OSCC/OPSCC, the CK19 test may be useful in identifying HR-HPV infection, the latter being related to HPV E7 potential to disrupt normal cytokeratin expression pattern.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 31%
Student > Master 4 31%
Student > Doctoral Student 1 8%
Professor 1 8%
Researcher 1 8%
Other 0 0%
Unknown 2 15%
Readers by discipline Count As %
Medicine and Dentistry 7 54%
Biochemistry, Genetics and Molecular Biology 2 15%
Agricultural and Biological Sciences 1 8%
Unknown 3 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 December 2015.
All research outputs
#3,287,527
of 6,790,336 outputs
Outputs from Infectious Agents and Cancer
#85
of 191 outputs
Outputs of similar age
#145,998
of 287,892 outputs
Outputs of similar age from Infectious Agents and Cancer
#10
of 20 outputs
Altmetric has tracked 6,790,336 research outputs across all sources so far. This one is in the 29th percentile – i.e., 29% of other outputs scored the same or lower than it.
So far Altmetric has tracked 191 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 42nd percentile – i.e., 42% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 287,892 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 20 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.