Saad A Khan1, Michael Burke2, Fang Zhu3, Dong-Hua Yang3, Cara Dubyk3, Ranee Mehra4, Miriam J Lango5, John A Ridge3, David J Sher2, Barbara Burtness6. 1. Fox Chase Cancer Center, United States; Stanford University, United States. 2. University of Texas Southwestern Medical Center, United States. 3. Fox Chase Cancer Center, United States. 4. Fox Chase Cancer Center, United States; University of Maryland, United States. 5. Fox Chase Cancer Center, United States; University of Texas, MD Anderson Cancer Center, Houston Texas, United States. 6. Fox Chase Cancer Center, United States. Electronic address: Barbara.Burtness@yale.edu.
Abstract
INTRODUCTION: Survivin is an inhibitor of apoptosis that is proposed as a target for anti-cancer therapy because of its high expression in cancer cells. It has potential as a prognostic and predictive biomarker of response to radiation and systemic therapies. We report its expression in head and neck squamous cell carcinoma (HNSCC) and its correlation with treatment response and survival. METHODS: We measured survivin protein expression in tumor specimens from 96 patients with HNSCC treated at Fox Chase Cancer Center, of whom 21 were p16+. Quantitative automated immunofluorescence was employed to score nuclear and cytoplasmic survivin in 5 tissue microarrays (TMAs) consisting of 316 H&N tumor cores and 107 control tissue cores. Survivin levels were then correlated to therapy response and survival outcomes. RESULTS: Using the median score as the cutoff, overall survival (OS) was significantly shorter for the group expressing higher survivin in nuclear (p = 0.013), cytoplasmic (p = 0.018) and total compartments (p = 0.006). No correlation was seen between survivin expression and patient sex or grade of tumor, T or N stage, or p16 status. Survivin expression in metastases did not significantly differ from that in primary tumors. Levels of p53 expression showed a significant positive correlation with higher survivin expression in the cytoplasm (p = 0.0264) and total compartments (p = 0.0264), but not in the nucleus (p = 0.0729). CONCLUSIONS: Survivin expression above the median is associated with shorter overall survival in HNSCC, including for patients treated with chemotherapy or radiation. p16 expression did not correlate with survivin levels.
INTRODUCTION: Survivin is an inhibitor of apoptosis that is proposed as a target for anti-cancer therapy because of its high expression in cancer cells. It has potential as a prognostic and predictive biomarker of response to radiation and systemic therapies. We report its expression in head and neck squamous cell carcinoma (HNSCC) and its correlation with treatment response and survival. METHODS: We measured survivin protein expression in tumor specimens from 96 patients with HNSCC treated at Fox Chase Cancer Center, of whom 21 were p16+. Quantitative automated immunofluorescence was employed to score nuclear and cytoplasmic survivin in 5 tissue microarrays (TMAs) consisting of 316 H&N tumor cores and 107 control tissue cores. Survivin levels were then correlated to therapy response and survival outcomes. RESULTS: Using the median score as the cutoff, overall survival (OS) was significantly shorter for the group expressing higher survivin in nuclear (p = 0.013), cytoplasmic (p = 0.018) and total compartments (p = 0.006). No correlation was seen between survivin expression and patient sex or grade of tumor, T or N stage, or p16 status. Survivin expression in metastases did not significantly differ from that in primary tumors. Levels of p53 expression showed a significant positive correlation with higher survivin expression in the cytoplasm (p = 0.0264) and total compartments (p = 0.0264), but not in the nucleus (p = 0.0729). CONCLUSIONS: Survivin expression above the median is associated with shorter overall survival in HNSCC, including for patients treated with chemotherapy or radiation. p16 expression did not correlate with survivin levels.
Authors: Anita Thomas; Kimberly Sue Slade; Roman A Blaheta; Sascha D Markowitsch; Philipp Stenzel; Katrin E Tagscherer; Wilfried Roth; Mario Schindeldecker; Martin Michaelis; Florian Rothweiler; Jaroslav Cinatl; Robert Dotzauer; Olesya Vakhrusheva; Maarten Albersen; Axel Haferkamp; Eva Juengel; Jindrich Cinatl; Igor Tsaur Journal: Cancers (Basel) Date: 2022-03-25 Impact factor: 6.639