Survivin Expression in Gastric Cancer: Association with Histomorphological Response to Neoadjuvant Therapy and Prognosis
Daniel Vallbohmer*1, Uta Drebber2, Paul M. Schneider1,3, Stephan E. Baldus4, Elfriede Bollschweiler1, Jan Brabender1, Stefan Monig1, Arnulf H. Hoelscher1, Ralf Metzger1
1Department of Surgery, University of Cologne, Cologne, Germany; 2Department of Pathology, University of Cologne, Cologne, Germany; 3Department of Visceral and Transplantation Surgery, University of Zurich, Zurich, Switzerland; 4Department of Pathology, University of Dusseldorf, Dusseldorf, Germany
Background: Neoadjuvant multimodality treatment is frequently applied to improve the poor prognosis associated with locally advanced gastric cancer. However, only patients with a major histopathologic response to neoadjuvant therapy seem to have a significant survival benefit. Predictive markers to allow individualization of multimodality treatment could be very helpful. We aimed to examine the association of survivin protein expression, an inhibitor of apoptosis, with histopathologic response to neoadjuvant chemotherapy and prognosis in patients with gastric cancer.Patients and
Methods: Forty patients (30 men, 10 women; median age 54.1 years) with gastric cancer (cT2-4, Nx, M0) received neoadjuvant chemotherapy (PLF-protocol: cisplatin, leucovorin, 5-FU; 2 cycles over 6 weeks). Afterwards, 38 patients underwent total gastrectomy, while 2 patients received definitive chemotherapy because of tumor progression. Histomorphologic regression was defined as major response when resected specimens contained less than 10 % vital tumor cells. Intratumoral survivin expression was determined by immunohistochemistry in pretherapeutic biopsies and posttherapeutic resection specimens and correlated with clinicopathologic parameters.
Results: The pre- and posttherapeutic intratumoral survivin protein expression was not associated with the histomorphologic regression. In addition, posttherapeutic survivin expression did not have any prognostic impact. However, a significant association was detected between pretherapeutic survivin levels and prognosis: patients with a higher survivin protein expression showed a significant survival benefit compared with patients having low intratumoral protein levels (5-year survival rate: 50% vs. 21%; p=0.038). In multivariate analysis pretherapeutic survivin expression was characterized as an independent prognostic marker, besides pN-status and histopathologic regression (p=0.008).
Conclusion: The pretherapeutic survivin protein expression seems to be an independent prognostic marker in the multimodality treatment of locally advanced gastric cancer. If intratumoral survivin levels can be used as a surrogate marker in the neoadjuvant therapy of gastric cancer, has to be validated in prospective trials.
