Open Access
ARTICLE
A Panel of Tumor Biomarkers to Predict Complete Pathological Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer
Chiara Dalle Fratte*, Silvia Mezzalira*, Jerry Polesel†, Elena De Mattia*, Antonio Palumbo‡, Angela Buonadonna§, Elisa Palazzari¶, Antonino De Paoli¶, Claudio Belluco#, Vincenzo Canzonieri‡** , Giuseppe Toffoli*, Erika Cecchin*
* Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
† Epidemiology and Statistics, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
‡ Pathology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
§ Medical Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
¶ Radiation Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
# Surgical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
** Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
Oncology Research 2020, 28(9), 847-855. https://doi.org/10.3727/096504021X16232280278813
Abstract
Pathological complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients
is related to a favorable prognosis. The identification of early biomarkers predictive of pathological complete
response would help optimize the multimodality management of the patients. A panel of 11 tumor-related
proteins was investigated by immunohistochemistry in the pretreatment biopsy of a group of locally advanced
rectal cancer patients to identify early biomarkers of pathological complete response to neoadjuvant chemoradiotherapy. A mono-institutional retrospective cohort of 95 stage II/III locally advanced rectal cancer patients
treated with neoadjuvant chemoradiotherapy and surgery was selected based on clinical–pathological characteristics and the availability of a pretreatment tumor biopsy. Eleven selected protein marker expression (MLH1,
GLUT1, Ki67, CA-IX, CXCR4, COX2, CXCL12, HIF1a, VEGF, CD44, and RAD51) was investigated. The
optimal cutoff values were calculated by receiver operating characteristic curve analysis. Classification and
regression tree analysis was performed to investigate the biomarker interaction. Patients presenting either Ki-67
or HIF1a or RAD51 below the cutoff value, or CXCR4 or COX2 above the cutoff value, were more likely
to get a pathological complete response. Classification and regression tree analysis identified three groups of
patients resulting from the combination of Ki-67 and CXCR4 expression. Patients with high expression of
Ki-67 had the lowest chance to get a pathological complete response (18%), as compared to patients with low
expression of both Ki-67 and CXCR4 (29%), and patients with low Ki-67 and high CXCR4 expression (70%).
Pretreatment Ki-67, CXCR4, COX2, HIF1a, and RAD51 in tumor biopsies are associated with pathological
complete response after neoadjuvant chemoradiotherapy in locally advanced rectal cancer. A combined evaluation of Ki-67 and CXCR4 would increase their predictive potential. If validated, their optimal cutoff could be
used to select patients for a tailored multimodality treatment.
Keywords
Cite This Article
Fratte, C. D., Mezzalira, S., Polesel, J., Mattia, E. D., Palumbo, A. et al. (2020). A Panel of Tumor Biomarkers to Predict Complete Pathological Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer.
Oncology Research, 28(9), 847–855.