ObjectiveAbnormal expression of Annexin A2 and S100A proteins has been reported to induce sensitivity/resistance to chemotherapy in a variety of cancers. The aim of this study was to evaluate the significance of Annexin A2 and S100A protein expression to predict response to neoadjuvant chemotherapy and prognostic significance of these protein expressions in bulky stage IB–IIA cervical cancer patients. MethodsPaired tumor samples (pre- and post-chemotherapy) were obtained from 68 patients who were treated with cisplatin-based neoadjuvant chemotherapy and radical hysterectomy at our hospital from 2006 to 2011. The expression of Annexin A2 and S100A proteins was analyzed by immunohistochemistry. ResultsThirty-six patients were identified as chemotherapy-response and 32 were non-response. (a). Protein expression in tumor cells: (1). Exposure of tumor cells to chemotherapy results in a change of Annexin A2 and S100A expression (P<0.05). (2). Annexin A2, S100A8 and S100A9 protein expression correlates with tumor response to chemotherapy (P<0.05). (b). Protein expression in stromal cells: (1). Expression of Annexin A2, S100A8 and S100A9 was increased, but S100A2 and S100A4 was decreased after exposure to chemotherapy (P<0.05). (2). Only S100A4 expression was associated with response to chemotherapy (P<0.05). Multivariate analysis revealed that tumor size (P=0.022), differentiation (P=0.000), Annexin A2 expression in stromal cells (P=0.009), and S100A8 expression in tumor cells (P=0.008) were independent prognostic factors for progression-free survival of cervical cancer patients. ConclusionsExpression of some of the measured proteins in tumor and stromal cells correlates with chemotherapy exposure, response to therapy, and progression-free survival.