J Cancer 2017; 8(7):1229-1237. doi:10.7150/jca.16980

Research Paper

The Prognostic Value of Tyrosine Kinase SRC Expression in Locally Advanced Rectal Cancer

Felix Rühlmann1, Manuel Nietert2, Thilo Sprenger1, Hendrik A. Wolff3, 4, Kia Homayounfar1, Peter Middel5, Hanibal Bohnenberger6, Tim Beissbarth2, B. Michael Ghadimi1, Torsten Liersch1, Lena-Christin Conradi1✉

1. Department of General, Visceral, and Pediatric Surgery, University Medical Center, Göttingen, Germany;
2. Department of Medical Statistics, University Medical Center, Göttingen, Germany;
3. University Medical Center, Göttingen, Germany;
4. Radiologie München, München, Germany;
5. Pathology Nordhessen, Kassel, Germany;
6. Department of Pathology, University Medical Center, Göttingen, Germany.

Abstract

The cellular sarcoma gene (SRC) is a proto-oncogene encoding for a tyrosine kinase. SRC expression was determined in locally advanced rectal adenocarcinoma tissue from pretreatment biopsies and resection specimens. The expression level was correlated with clinicopathological parameters to evaluate the predictive and prognostic capacity.

For this monocentric analysis 186 patients with locally advanced rectal cancer (median: 63.7 years; 130 men (69.9%), 56 women (30.1%)) were included. Patients with a carcinoma of the upper third of the rectum were treated with primary tumor resection (n=27; 14.5%). All other patients received a preoperative chemoradiotherapy (CRT) with 50.4 Gy and concomitant 5-fluorouracil (5-FU) or 5-FU+oxaliplatin followed by postoperative chemotherapy with 5-FU or 5-FU+oxaliplatin. SRC expression was determined with immunohistochemical staining from pretreatment biopsies (n=152) and residual tumor tissue from the resection specimens (n=163). The results were correlated with clinicopathological parameters and long-term follow-up.

The expression of SRC was determined in pretherapeutic biopsies (mean H-Score: 229) and resection specimens (mean H-Score: 254). High SRC expression in pretherapeutic tumor samples significantly correlated with a negative postoperative nodal status (p=0.005). Furthermore an increased protein expression in residual tumor tissue was associated with fewer distant metastases (p=0.04). The overexpression of SRC in pretreatment tumor biopsies showed also a trend for a longer cancer-specific survival (CSS; p=0.05) and fewer local relapses (p=0.06) during long-term follow-up.

High SRC expression in rectal cancer seems to be associated with a better long-term outcome. This finding could help in the future to stratify patients for a recurrence risk adapted postoperative treatment.

Keywords: SRC, rectal cancer, tyrosine kinase, preoperative chemoradiotherapy, biomarker, targeted therapy.

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How to cite this article:
Rühlmann F, Nietert M, Sprenger T, Wolff HA, Homayounfar K, Middel P, Bohnenberger H, Beissbarth T, Ghadimi BM, Liersch T, Conradi LC. The Prognostic Value of Tyrosine Kinase SRC Expression in Locally Advanced Rectal Cancer. J Cancer 2017; 8(7):1229-1237. doi:10.7150/jca.16980. Available from http://www.jcancer.org/v08p1229.htm