engleski

Nuclear EGFR strong expression in laryngeal squamous cell carcinoma affects a more aggressive biological behaviour

Aim of the study: Membrane EGFR (mEGFR) protein overexpression is frequently found in the head and neck squamous cell carcinoma (HNSCC). It has been found that mEGFR upon stimulation translocates to nucleus and its nuclear localisation is associated with poor prognosis in many cancers. The main focus of this study is to asses if nuclear EGFR (nEGFR) expression affects biologically more aggressive tumor behaviour in comparison to mEGFR expression in laryngeal SCC. Material and Methods: We examined 42 laryngeal squamous cell carcinomas (SCC) for nEGFR and mEGFR expression as well as cell cycle proliferative markers Ki-67, p53, cyclin D1 using immunohistochemistry. Results: In our study group, we found in 28.57% (12/42) SCC cases a strong (3+) nEGFR expression, 64.28% (27/42) SCC had weak to moderate (1+/2+) nEGFR expression while 7.14% (3/42) cases were negative for nEGFR. The majority of patients with SCC had strong (3+) mEGFR (52.38% or 22/42) expression and 45.23% (19/42) had weak to moderate (1+/2+) mEGFR expression and one case (1/42) was negative for mEGFR. The mean values ± standard deviation (%) of Ki-67, p53 and cyclin D1 expression in our study group were 39.04 ± 18.08, 38.88 ± 32.22 and 43.82 ± 18.34, respectively. When assessing the association of nEGFR with mEGFR and cell cycle proliferation markers there was statistically significant negative correlation between nEGFR and mEGFR expression (τ = -0.389 ; P = 0.002) and statistically significant negative correlation between nEGFR and cyclin D1 (τ = -0.274 ; P = 0.032). In the analysis of mEGFR correlations with the examined cell proliferation markers there were no statistically significant associations. We also observed that higher number of patients with strong nEGFR expression and concomitant negative/weak to moderate mEGFR expression died (70% or 7/10 patients) in comparison to number of patients with strong mEGFR expression and negative/weak to moderate nEGFR expression (40% or 8/20 patients). Moreover, univariate statistical analysis showed a statistically significant correlation between strong nEGFR protein expression with worse overall survival in laryngeal SCC, alone or in co-expression with strong cyclin D1 and high Ki-67 (P=0.025, P=0.046, P=0.043, respectively). However, there was no statistically significant difference in the overall survival, when we analyzed strong mEGFR expression, alone or in co- expression with cyclin D1 and Ki-67 cell cycle proteins (P=0.953, P=0.731, P=0.647, respectively). Conclusion: Our data indicate that nuclear EGFR cellular localization with strong expression might influence the more aggressive biological behaviour of laryngeal SCC carcinoma with poor patient survival.

Immunohistochemistry ; Epidermal Growth Factor Receptor ; Laryngeal Cancer ; Carcinogenesis.

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