Histologic pattern of invasion and epithelial-mesenchymal phenotype predict prognosis in squamous carcinoma of the head and neck

Abstract

Introduction: Disruption of E-cadherin function and increased expression of vimentin and the transcriptional oncogene, SOX2, are thought to characterize epithelial to mesenchymal transition (EMT) in HNSCC that contributes to invasive and metastatic behavior. To determine if such changes relate to prognosis or host immune response, expression of these markers and correlations with clinical characteristics, histologic worst pattern of invasion (WPOI) and tumor infiltrating lymphocytes (TIL) and survival were assessed. Methods: Immunohistologic expression of markers was determined in tissue microarrays from 274 previously untreated HNSCC patients. Expression was correlated with levels of TILs in microcores and WPOI in biopsy specimens. Correlations were assessed by Kruskal-Wallis testing and Spearman correlation coefficients where appropriate. Overall and relapse-free survival were analyzed with Cox proportional hazards models. Median follow up was 60.0 months. Results: Loss of E-cadherin expression was significantly associated with low or absent SOX2 expression (R=0.433, p<0.0001). SOX2 expression and low grade WPOI were significantly associated with favorable overall (OS) and relapse free (RFS) survival in multivariable analysis. E-cadherin expression did not correlate with TILs, however WPOI score correlated indirectly with CD4, CD8, and FoxP3 levels. When grouped by primary treatment, lower grades (1,2) of WPOI predicted improved RFS and OS in patients treated with primary surgery but not for patients treated with chemoradiation. Conclusion: The findings suggest that SOX2 expression and WPOI are significant prognostic factors and that WPOI correlates with decreased T cell infiltration. The combination of markers and TILs might be useful in selecting patients for primary surgery.

Histopathologic grading and its relationship with outcome in oral tongue squamous cell carcinoma

“…Also, EMT is a feature of cancer stem cells (CSC), which are strongly related to recurrence and therapeutic resistance. Identification of CSC in HNSCC associated to EMT, invasion, metastasis and therapeutic resistance suggests that the degree of EMT can affect tumor growing features expressed by histologic patterns of invasion, and maybe it can affect response to treatment and general prognosis 29,30 …”

Slug Is A Surrogate Marker of Epithelial to Mesenchymal Transition (EMT) in Head and Neck Cancer

“…In previous in vitro studies in HNC cells we observed that EMT is of high relevance in tumor progression and therapy resistance [ 13 , 14 , 15 , 16 , 17 , 18 ]. However, the clinical relevance of EMT in cancer has been questioned as EMT is difficult to measure in tumor samples and EMT is frequently not observed in histopathological examinations of cancer tissues by pathologists [ 31 , 32 ]. As a consequence, surrogate markers for EMT, e.g., loss of E-cadherin expression or increased vimentin expression were used in cancer tissue [ 19 , 33 , 34 ].…”

Discordant Immune Marker Expression Between Preoperatively Biopsied and Matched Surgically Resected Specimens in Patients With Oral Squamous Cell Carcinoma

“…Recent researches have shown that programmed death ligand 1 (PD-L1) expression in tumor cells and the density of tumor-associated immune cells (TAICs) can serve as biomarkers for survival outcomes in oral squamous cell carcinoma (OSCC) [1][2][3][4][5]. We also examined surgically resected specimens from 103 OSCC patients who underwent definitive surgery and reported that PD-1+ TAICs in the tumor microenvironment and CD68+ TAICs in the intratumoral area could act as positive and negative biomarkers for predicting overall survival outcomes, respectively [6].…”