Phospho-ERK levels as predictors for chemotherapy of rectal carcinoma

// Susanne Holck 1 , Louise Laurberg Klarskov 2 and Lars-Inge Larsson 1, 3 1 Department of Pathology, Copenhagen University Hospital Hvidovre, DK-2650 Hvidovre, Denmark 2 Department of Pathology, Copenhagen University Hospital Herlev, DK-2730 Herlev, Denmark 3 Clinical Research Center, Copenhagen University Hospital Hvidovre, DK-2650 Hvidovre, Denmark Correspondence to: Lars-Inge Larsson, email: lars.inge.larsson@regionh.dk Keywords: rectal cancer; chemotherapy; fluorouracil; ERK; phosphorylation Received: January 13, 2019      Accepted: February 15, 2019      Published: March 01, 2019 ABSTRACT Treatment of rectal cancer has been vastly improved by advances in surgery and radiochemotherapy but remains an important cause of morbidity and mortality worldwide. A particular problem is the lack of predictive markers that can help to individualize treatment. The growth- and apoptosis-regulating signaling molecules ERK 1 and 2 are important to cancer growth and progression. They are activated through phosphorylation, which is initiated by a cascade involving the EGF receptor and RAS as upstream regulators. Moreover, in vitro studies indicate that phospho-ERKs interfere with 5-fluorouracil-based chemotherapy. Recently, we showed that high levels of phospho-ERKs in rectal cancer cells predict poor responses to neoadjuvant (preoperative) radiochemotherapy. We now report that preoperative phospho-ERK levels also can subdivide high-risk rectal cancer patients into a favorable and a poor prognostic group with respect to recurrence-free survival. Importantly, phospho-ERK levels were of predictive significance only in high-risk patients, who received adjuvant (postoperative) chemotherapy, but not in high-risk patients not receiving such therapy. Our results suggest that high cancer cell levels of phospho-ERK predict poor responsiveness to both preoperative and postoperative chemotherapy of rectal cancer.