Proliferative index activity in oral squamous cell carcinoma: indication for postoperative radiotherapy?

Abstract

The predictive value of the Ki-67 labelling index and its relationship with radiosensitivity in oral squamous cell carcinoma (SCC) remains controversial. We sought to evaluate whether the expression of Ki-67 antigen found in SCC of the tongue and the floor of the mouth is an indication for postoperative radiotherapy (PORT). The first study group included 34 patients who were treated only with primary surgery, while the second group included 26 patients who underwent primary surgery combined with PORT. The correlation between Ki-67 expression and loco-regional recurrence, as well as the 5-year disease-specific survival, was assessed in the two groups. Cases of high-proliferative tumours showed a significantly higher risk of loco-regional recurrence ( P = 0.018) and a poorer prognosis ( P = 0.001) only in the 34 patients treated with surgery alone. In multivariate Cox regression analysis, high Ki-67 expression was an independent predictor of loco-regional recurrence (HR 5.42, P = 0.029) and disease-specific survival (HR 9.02, P = 0.004). The correlation between Ki-67 expression and the risk of loco-regional recurrence in SCC of the tongue and the floor of the mouth may be useful in the selection of patients at a higher risk of recurrence who would benefit from PORT, despite adequate margins of resection and early stage of the disease.

Introduction

Oral squamous cell carcinoma (SCC) is most frequently localised in the tongue and floor of the mouth and is an invasive tumour with a high rate of nodal metastasis. Despite continuous improvements in treatment modalities, the prognosis for oral SCC remains poor. The 5-year overall survival (OS) rate ranges from 32.8% to 56% and the 5-year disease-specific survival (DSS) rate varies from 41% to 74%.

For most cases of oral SCC, the preferred method of treatment is surgery, often combined with postoperative radiotherapy (PORT). PORT is indicated to prevent loco-regional recurrence (LRR) in patients with a high risk of the cancer spreading, and is essential in cases with positive resection margins and extracapsular extension (ECE) of nodal disease. Relative indications for PORT include inadequate margins of resection (<5 mm), the presence of more than two positive lymph nodes, nodal metastasis at the IV and V cervical level, pT3–pT4 tumours with negative surgical margins, and perineural involvement, as well as microvascular emboli of the cancer cells.

The evaluation of factors predicting tumour radiosensitivity enables the selection of patients who may benefit from PORT despite the early stage of the disease and adequate surgical margins. According to the law of Bergonié and Tribondeau, the radiosensitivity of cells is proportional to their proliferative activity. Moreover, the number of proliferating cells characterises the rate of tumour growth, and its malignancy reflects the response to therapy. For example, the fraction of dividing cells can be evaluated using proliferation markers, such as Ki-67 antigen, which likely takes part in the synthesis of ribosomal RNA. The expression of Ki-67 antigen is observed in every phase of the cell cycle except the G 0 phase. Nevertheless, the predictive value of the Ki-67 labelling index (LI) and its relationship with radiosensitivity in oral SCC is considered controversial. The aim of this study was to evaluate whether the expression of Ki-67 antigen in SCC of the tongue and the floor of the mouth is an indication for PORT.

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Jan 19, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Proliferative index activity in oral squamous cell carcinoma: indication for postoperative radiotherapy?
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