Prognostic relevance of Src activation in stage II-III colon cancer

Publication date: Available online 7 June 2017
Source:Human Pathology
Author(s): Julia Martinez Perez, Iker Lopez-Calderero, Carmen Saez, Marta Benavent, Maria L. Limon, Reyes Gonzalez-Exposito, B. Soldevilla, Maria C. Riesco-Martinez, Javier Salamanca, Amancio Carnero, Rocio Garcia-Carbonero
Src belongs to a family of cytoplasmic tyrosine kinases that play a key role in tumor initiation and progression. Src activation has been associated with a more aggressive neoplastic phenotype and induces resistance to platinum agents in preclinical models. The aim of our study was to assess the prognostic and/or predictive value of Src activation in stage II-III colon cancer patients. pSrc expression was assessed in paraffin-embedded tumor samples by immunohistochemistry (phospho Y418, ab4816, Abcam). Cases were classified by staining intensity in four categories: no staining (0), weak (1+), moderate (2+) and intense (3+) staining. A total of 487 patients were evaluated (240 stage II, 247 stage III), of whom 298 (61%) had received adjuvant chemotherapy. Staining was absent in 78 (16%), weak in 262 (54%), moderate in 103 (21%) and intense in 44 (9%). High pSrc expression was significantly associated with decreased 5-year disease-free survival (39% vs 63% for patients with high vs low pSrc expression, HR=0.56, P=.005) and overall survival (58% vs 74%, HR=0.55, P=.02). Multivariate analysis confirmed pSrc expression as a significant prognostic factor both for DFS and OS, independent of age, gender, tumor stage, bowel obstruction/perforation or adjuvant chemotherapy. These findings illustrate the relevance of Src activation in colon cancer biology, conferring a poor prognosis to early stage colon cancer patients regardless of adjuvant chemotherapy. Our findings may help improve prognostic stratification of patients for clinical decissions, and open new avenues for potential pharmacological manipulation that may eventually improve patients' outcomes.



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