Abstract
ObjectiveTo explore the role of Major Vault Protein (MVP) in oral cavity squamous cell carcinoma patients.Subjects and Methods131 consecutive patients suffering from oral cavity squamous cell carcinoma were included in the study. In the whole series, the mean follow-up for survivors was 123.11 ± 40.36 months. Patients in tumour stages I and II were referred to surgery; patients in stage III-IV to postoperative radiotherapy (mean dose = 62.13 ± 7.74 Gy in 1.8–2 Gy/fraction). MVP expression was studied by immunohistochemistry in paraffin-embedded tumour tissue.ResultsMVP expression was positive in 112 patients (85.5%) and no relation was found with clinic pathological variables. MVP overexpression (those tumours with moderate or strong expression of the protein) was related to insulin-like growth factor receptor-1 (IGF-1R) expression (P = 0.014). Tumour stage of the disease was the most important prognostic factor related to survival. Tumours overexpressing MVP and IGF-1R were strongly related to poor disease-free survival (P = 0.008, Exp(B) = 2.730, CI95% (1.302-5.724)) and cause-specific survival (P = 0.014, Exp(B) = 2.570, CI95% (1.215-5.437)) in patients achieving tumour stages III-IV, in multivariate analysis.ConclusionsMVP and IGF-1R expression were related in oral squamous cell carcinoma and conferred reduced long-term survival in patients suffering from advanced stages of the disease.
Highlights
Oral carcinoma is commonly treated by surgery or radiotherapy as local treatments
Major Vault Protein (MVP) expression was positive in 112 patients (85.5%) and no relation was found with clinic pathological variables
Tumours overexpressing MVP and Insulin-like growth factor-1 receptor (IGF-1R) were strongly related to poor disease-free survival (P = 0.008, Exp(B) = 2.730, CI95% (1.302-5.724)) and cause-specific survival (P = 0.014, Exp (B) = 2.570, CI95% (1.215-5.437)) in patients achieving tumour stages III-IV, in multivariate analysis
Summary
Oral carcinoma is commonly treated by surgery or radiotherapy as local treatments. long-term survival is improving with advances in therapy, outcomes in locally advanced cases remain suboptimal. MVP has been associated to resistance to radiotherapy [4], probably due to its role in preventing apoptosis by inhibiting the COP-1/p53 axis [5]. Various DNA damaging agents, including ultraviolet irradiation, induce increased MVP transcription and protein levels [6]. This suggests that vaults may have a role in facilitating DNA repair processes, which is consistent with previous work showing that VPARP- and TEP1-deficient mice have an increased incidence of carcinogen-induced colon tumours [7]. The underlying mechanisms behind this observation are not understood and the role of MVP in oral cavity squamous cell carcinoma has not been deeply studied, especially in combination with other biological markers
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