p16 Immunohistochemistry As a Standalone Test for Risk Stratification in Oropharyngeal Squamous Cell Carcinoma

Most nasopharyngeal carcinomas (NPCs) in a high-incidence population are driven by Epstein-Barr virus (EBV) infection. EBV-associated malignancies have increased expression of the programmed death-ligand 1 (PD-L1). Immunotherapy agents targeting the PD-1/PD-L1 pathway have achieved durable treatment effects in patients with various cancer types including EBV-associated malignancies. In this study, we sought to investigate PD-L1 expression in a cohort of patients with NPCs from the Philippines. Fifty-six NPCs were studied for PD-L1, p16, and DNA mismatch repair (MMR) deficiency by immunohistochemistry. One case with MMR deficiency was also assessed for microsatellite instability (MSI) by polymerase chain reaction. EBV and human papillomavirus (HPV) status were tested by in situ hybridization. All NPCs were p16 negative. Three of the 56 NPCs (5%) were EBV negative (EBV-) and HPV negative, while one NPC (1/56, 2%) was EBV positive and showed MSI (EBV?/MSI). Positive PD-L1 expression (PD-L1?), defined as membranous staining in C1% tumor cells, was seen in 64% (36/56) of NPCs. All three EBV-NPCs were PD-L1? as was the EBV?/MSI NPC. PD-L1? was seen significantly more often in NPCs from non-smokers than those from smokers (23/28, 82% vs 9/18, 50%; P = 0.047). PD-L1? was not associated with pT, pN, distant metastasis, or clinical stage (P [ 0.05). PD-L1? was not associated with overall survival (P = 0.473). In summary, our results show frequent PD-L1 expression in NPCs regardless of EBV status and a preferential PD-L1 expression in non-smokers. MSI and HPV positivity are exceedingly rare in NPCs.

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“…All 56 NPCs were negative for p16, the surrogate marker for HPV [26]. Fifty-three of the 56 NPCs (95%) were EBV positive ( Table 2; Fig.…”

Section: Hpv Ebv and Msi In Nasopharyngeal Carcinomasmentioning

confidence: 97%

Programmed Death-Ligand 1 Expression, Microsatellite Instability, Epstein–Barr Virus, and Human Papillomavirus in Nasopharyngeal Carcinomas of Patients from the Philippines

Chang

Chiosea

Altman

et al. 2016

Head and Neck Pathol

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“…Positivity for transcriptionally-active high risk HPV (but not simply HPV DNA alone) favors an oropharyngeal primary, indicates a better prognosis and may be necessary to stratify patients for clinical trials [19]. Strong and diffuse, nuclear and cytoplasmic p16 staining by IHC is an excellent surrogate marker for SCCs harboring transcriptionally-active virus (''HPV-related'' SCC) when the primary site is oropharyngeal and is a wellestablished standalone prognostic biomarker in oropharyngeal SCC [20]. It is also easy to perform and interpret.…”

Section: Squamous Cell Carcinoma Of Unknown Primary In the Era Of Hummentioning

confidence: 99%

Approach to Metastatic Carcinoma of Unknown Primary in the Head and Neck: Squamous Cell Carcinoma and Beyond

Chernock

Lewis

2015

Head and Neck Pathol

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“…Both positive and negative control slides were prepared. The proportion of tumor cells demonstrating nuclear and cytoplasmic p16 staining were categorized dichotomously as either p16 positive ([70 % tumor cells exhibiting strong and diffuse nuclear and cytoplasmic staining) or p16 negative (\70 % tumor cells exhibiting strong and diffuse nuclear and cytoplasmic staining) [17].…”

Section: P16 Ink4amentioning

confidence: 99%

Mutation and Transcriptional Profiling of Formalin-Fixed Paraffin Embedded Specimens as Companion Methods to Immunohistochemistry for Determining Therapeutic Targets in Oropharyngeal Squamous Cell Carcinoma (OPSCC): A Pilot of Proof of Principle

Saba

Wilson

Doho

et al. 2014

Head and Neck Pathol

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The role of molecular methods in the diagnosis of head and neck cancer is rapidly evolving and holds great potential for improving outcomes for all patients who suffer from this diverse group of malignancies. However, there is considerable debate as to the best clinical approaches, particularly for Next Generation Sequencing (NGS). The choices of NGS methods such as whole exome, whole genome, whole transcriptomes (RNA-Seq) or multiple gene resequencing panels, each have strengths and weakness based on data quality, the size of the data, the turnaround time for data analysis, and clinical actionability. There have also been a variety of gene expression signatures established from microarray studies that correlate with relapse and response to treatment, but none of these methods have been implemented as standard of care for oropharyngeal squamous cell carcinoma (OPSCC). Because many genomic methodologies are still far from the capabilities of most clinical laboratories, we chose to explore the use of a combination of off the shelf targeted mutation analysis and gene expression analysis methods to complement standard anatomical pathology methods. Specifically, we have used the Ion Torrent AmpliSeq cancer panel in combination with the NanoString nCounter Human Cancer Reference Kit on 8 formalin-fixed paraffin embedded (FFPE) OPSCC tumor specimens, (4) HPVpositive and (4) HPV-negative. Differential expression analysis between HPV-positive and negative groups showed that expression of several genes was highly likely to correlate with HPV status. For example, WNT1, PDGFA and OGG1 were all over-expressed in the positive group. Our results show the utility of these methods with routine FFPE clinical specimens to identify potential therapeutic targets which could be readily applied in a clinical trial setting for clinical laboratories lacking the instrumentation or bioinformatics infrastructure to support comprehensive genomics workflows. To the best of our knowledge, these preliminary experiments are among the earliest to combine both mutational and gene expression profiles using Ion Torrent and NanoString technologies. This reports serves as a proof of principle methodology in OPSCC.Electronic supplementary material The online version of this article

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p16 Immunohistochemistry As a Standalone Test for Risk Stratification in Oropharyngeal Squamous Cell Carcinoma

Cited by 210 publications

References 29 publications

Programmed Death-Ligand 1 Expression, Microsatellite Instability, Epstein–Barr Virus, and Human Papillomavirus in Nasopharyngeal Carcinomas of Patients from the Philippines

Programmed Death-Ligand 1 Expression, Microsatellite Instability, Epstein–Barr Virus, and Human Papillomavirus in Nasopharyngeal Carcinomas of Patients from the Philippines

Approach to Metastatic Carcinoma of Unknown Primary in the Head and Neck: Squamous Cell Carcinoma and Beyond

Mutation and Transcriptional Profiling of Formalin-Fixed Paraffin Embedded Specimens as Companion Methods to Immunohistochemistry for Determining Therapeutic Targets in Oropharyngeal Squamous Cell Carcinoma (OPSCC): A Pilot of Proof of Principle

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