Tim N Beck1,2, Chad H Smith1,3, Douglas B Flieder4, Thomas J Galloway5, John A Ridge1,6, Erica A Golemis1,2, Ranee Mehra1,3. 1. Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, Pennsylvania. 2. Molecular and Cell Biology & Genetics Program, Drexel University College of Medicine, Philadelphia, Pennsylvania. 3. Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. 4. Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. 5. Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. 6. Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Abstract
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is potentially curable, but treatment planning remains a challenge. Oncogenic human papillomavirus (HPV)-positive disease is often associated with a good prognosis compared with HPV-negative disease. However, some HPV-positive HNSCC recurs, often with distant metastases and significant treatment resistance. METHODS AND RESULTS: We performed p16 immunohistochemistry (IHC), in situ hybridization (ISH) for high-risk HPV, and comprehensive genomic profiling on oropharyngeal HNSCC with basaloid features and particularly aggressive disease course, noting a rare genetic event: a deleting mutation (exons 5-17) of the tumor suppressor and dominant cell cycle regulator retinoblastoma 1 (RB1). Genomic and transcriptomic data available through FoundationOne and The Cancer Genome Atlas (TCGA) were reviewed for additional HNSCC cases with RB1 alterations. CONCLUSION: RB1 alterations may have important prognostic implications, particularly in the context of high p16 expression, in both HPV-positive and HPV-negative HNSCC.
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is potentially curable, but treatment planning remains a challenge. Oncogenic humanpapillomavirus (HPV)-positive disease is often associated with a good prognosis compared with HPV-negative disease. However, some HPV-positive HNSCC recurs, often with distant metastases and significant treatment resistance. METHODS AND RESULTS: We performed p16 immunohistochemistry (IHC), in situ hybridization (ISH) for high-risk HPV, and comprehensive genomic profiling on oropharyngeal HNSCC with basaloid features and particularly aggressive disease course, noting a rare genetic event: a deleting mutation (exons 5-17) of the tumor suppressor and dominant cell cycle regulator retinoblastoma 1 (RB1). Genomic and transcriptomic data available through FoundationOne and The Cancer Genome Atlas (TCGA) were reviewed for additional HNSCC cases with RB1 alterations. CONCLUSION:RB1 alterations may have important prognostic implications, particularly in the context of high p16 expression, in both HPV-positive and HPV-negative HNSCC.
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