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Molecular Predictors of Response to Neoadjuvant Chemoradiation for Rectal Cancer

Kundel, Yulia, MD*,†; Nasser, Nicola, J., MD, PhD‡,§; Rath-Wolfson, Lea, MD†,∥; Purim, Ofer, MD*,†; Yanichkin, Natalia, MD; Brenner, Ronen, MD; Zehavi, Tanya, MD#; Nardi, Yuval, MD**; Fenig, Eyal, MD*,†; Sulkes, Aaron, MD*,†; Brenner, Baruch, MD*,†

American Journal of Clinical Oncology: June 2018 - Volume 41 - Issue 6 - p 613–618
doi: 10.1097/COC.0000000000000337
Original Articles: Gastrointestinal

Objectives: To determine whether the expression of specific molecular markers in the rectal cancer biopsies prior to treatment, can correlate with complete tumor response to chemoradiotherapy (CRT) as determined by the pathology of the surgical specimen.

Methods: We retrospectively examined pretreatment rectal biopsies of patients aged 18 years or older with locally advanced rectal cancer who had been treated with neoadjuvant CRT and surgical resection in our tertiary-care, university-affiliated medical center, between January 2001 and December 2011. Samples were analyzed for expression of B-cell lymphoma 2, P53, Ki67, epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor, and the tumor regression grade after CRT and radical surgery.

Results: Forty-seven patients were included in the final analysis. Main outcome measures were the correlation between the expression of the molecular markers tested in the pretreatment biopsy, and complete tumor response. Complete pathologic response after CRT was attained in 27% of the patients. Percentage of cells expressing EGFR in the pretreated biopsies of patients having complete pathologic response after CRT and surgery was 33.08±7.87% compared to 19±15.36% (P=0.38), 6.66±2.83% (P<0.003), and 12.5±4.93% (P=0.033) in patients with partial response and tumor regression grades of 2, 3, and 4, respectively. The other molecular markers tested in the pretreatment biopsy did not corresponded with complete pathologic response.

Conclusions: EGFR expression pattern in the pretreatment biopsies of rectal tumors can assist in identifying patients who will benefit from neoadjuvant CRT.

*Institute of Oncology, Davidoff Cancer Center, Beilinson Hospital

Department of Pathology, Rabin Medical Center, Hasharon Hospital, Petach Tikva

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv

§Faculty of Medicine in the Galilee, Bar-Ilan University

Oncology Institute, Ziv Medical Center, Safed

Institute of Oncology, Wolfson Medical Center, Holon

#Meir Medical Center, Kfar Saba

**Faculty of Industrial Engineering and Management, Technion—Israel Institute of Technology, Haifa, Israel

Y.K., N.J.N., L.R.-W., and O.P. contributed equally.

The authors declare no conflicts of interest.

Reprints: Baruch Brenner, MD, Institute of Oncology, Davidoff Center, Beilinson Hospital, Petach Tikva 49100, Israel. E-mail:

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