Zuzana Saidak1, Florian Clatot2, Denis Chatelain3, Antoine Galmiche4. 1. Equipe CHIMERE, Université de Picardie Jules Verne, Amiens, France; Laboratoire d'Oncobiologie Moléculaire, Centre de Biologie Humaine, CHU Amiens, France. Electronic address: Saidak.Zuzana@chu-amiens.fr. 2. INSERM U1245/IRON Team, Rouen, France; Centre Henri Becquerel, Rouen, France. 3. Equipe CHIMERE, Université de Picardie Jules Verne, Amiens, France; Laboratoire d'Anatomopathologie, CHU Amiens, France. 4. Equipe CHIMERE, Université de Picardie Jules Verne, Amiens, France; Laboratoire de Biochimie, Centre de Biologie Humaine, CHU Amiens, France. Electronic address: Galmiche.Antoine@chu-amiens.fr.
Abstract
OBJECTIVES: Perineural invasion (PNI) is a common histopathological finding in head and neck squamous cell carcinoma (HNSCC). We aimed to explore the molecular mechanisms involved in PNI and the role of PNI as an aggressive pathological feature. MATERIALS AND METHODS: We used data from The Cancer Genome Atlas (TCGA) to relate the histological presentation of 528 HNSCC tumours to clinical, whole genome expression and proteomic data. RESULTS: We identified a specific gene expression profile highly enriched in genes related to muscle differentiation/function and associated with PNI in HNSCC. We explored the clinical significance of this profile in three groups of HNSCC tumours stratified according to their low, intermediate or high risk of post-surgical recurrence. In the "low-risk" group, defined as tumours indicated for surgery without adjuvant radiotherapy (n = 51), the PNI gene expression profile identified a subset of HNSCC with a higher rate of tumour recurrence, decreased Disease Free Survival (DFS) and Overall Survival (OS) (p < 0.0001 and p = 0.0064, respectively). Comparable results were observed in "intermediate risk" tumours (n = 112), but not in "high risk" tumours (n = 147), whose prognosis was driven by the presence of lymph node extracapsular spread. Finally, we found that tumours with histological PNI had increased activation levels of the Akt/PKB and mTOR (mammalian Target Of Rapamycin) kinases. CONCLUSION: PNI is characterised by a specific gene expression profile and distinct biological characteristics. Analysing the PNI gene expression profile holds potential for therapeutic stratification of HNSCC and identification of a subset of tumours with a higher risk of recurrence.
OBJECTIVES: Perineural invasion (PNI) is a common histopathological finding in head and neck squamous cell carcinoma (HNSCC). We aimed to explore the molecular mechanisms involved in PNI and the role of PNI as an aggressive pathological feature. MATERIALS AND METHODS: We used data from The Cancer Genome Atlas (TCGA) to relate the histological presentation of 528 HNSCC tumours to clinical, whole genome expression and proteomic data. RESULTS: We identified a specific gene expression profile highly enriched in genes related to muscle differentiation/function and associated with PNI in HNSCC. We explored the clinical significance of this profile in three groups of HNSCC tumours stratified according to their low, intermediate or high risk of post-surgical recurrence. In the "low-risk" group, defined as tumours indicated for surgery without adjuvant radiotherapy (n = 51), the PNI gene expression profile identified a subset of HNSCC with a higher rate of tumour recurrence, decreased Disease Free Survival (DFS) and Overall Survival (OS) (p < 0.0001 and p = 0.0064, respectively). Comparable results were observed in "intermediate risk" tumours (n = 112), but not in "high risk" tumours (n = 147), whose prognosis was driven by the presence of lymph node extracapsular spread. Finally, we found that tumours with histological PNI had increased activation levels of the Akt/PKB and mTOR (mammalian Target Of Rapamycin) kinases. CONCLUSION: PNI is characterised by a specific gene expression profile and distinct biological characteristics. Analysing the PNI gene expression profile holds potential for therapeutic stratification of HNSCC and identification of a subset of tumours with a higher risk of recurrence.
Authors: Flora Yan; Yi-Shing Lisa Cheng; Nora Katabi; Shaun A Nguyen; Huey-Shys Chen; Patrick Morgan; Kathy Zhang; Angela C Chi Journal: Head Neck Pathol Date: 2021-03-31