Background: The benefits of induction chemotherapy in oral squamous cell carcinoma (OSCC) remain to be clearly defined, as trials to date have not shown a major survival benefit when induction chemotherapy plus standard therapy is compared with standard therapy alone. Induction chemotherapy is likely to be effective for biologically distinct subgroups of patients and biomarker development might lead to identification of the patients whose tumors are to respond to a particular treatment. This study investigated the prognostic and predictive values of evaluating Annexin A1 expression in OSCC patients who were treated in a randomized trial comparing surgery and post-operative radiotherapy with induction chemotherapy of docetaxel, cisplatin and 5-fluorouracil (TPF) followed by surgery and post-operative radiotherapy.
Methods: Immunohistochemical staining for Annexin A1 was performed in pretreatment biopsy specimens from 232 out of 256 clinical stage III/IVA OSCC patients randomized to the clinical trial. Annexin A1 index was estimated as the proportion of tumor cells with Annexin A1 cellular membrane and cytoplasm staining.
Results: There was a significant correlation between decreased Annexin A1 expression and worse pathologic differentiation grade ( P = 0.015) in OSCC patients. A low Annexin A1 expression predicted a better survival, especially disease-free survival ( P = 0.036) and locoregional recurrence-free survival ( P = 0.031) compared to high Annexin A1 expression in OSCC patients. Patients with moderately/poorly pathologic differentiation grade whose tumors had low Annexin A1 expression benefited from TPF induction chemotherapy on distant metastasis-free survival ( P = 0.048) and overall survival ( P = 0.078).
Conclusions: OSCC patients with moderately/poorly pathologic differentiation grade and low Annexin A1 expression could benefit from the addition of TPF induction chemotherapy to surgery and post-operative radiotherapy. Annexin A1 expression might be used as a biomarker in further validation studies to select OSCC patients with moderately/poorly pathologic differentiation grade that could benefit from induction therapy.