P-0201 - Expression of sonic hedgehog and smoothened in metastatic colorectal cancer

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Colon Cancer
Rectal Cancer
Pathology/Molecular Biology
Presenter Vicente Valentí
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors V. Valentí, J. Ramos, C. Pérez, L. Capdevila, P. Marcos, E. Martí
  • Hospital Santa Tecla, Tarragona-Vendrell/ES

Abstract

Introduction

Disregulation of the Hedgehog pathway may result in malignant cell transformation. We conducted a study on the expression of Sonic Hedgehog (SHH) and its Smoothened (SMO) receptor in tumor samples from patients with advanced colorectal cancer. We analyzed the relationship between the expression of SHH-SMO and clinicopathological factors.

Methods

The study was designed as a pilot study of prognostic factors. Consecutive patients with advanced colorectal cancer, treated in a real-world setting, were selected in a single Institution in Spain. Inferential statistics (Student-Fisher T and Chi-square) was used in order to ascertain the relationship between SHH-SMO expression and clinicopathological factors.

Results

Data from 21 consecutive patients with advanced colorectal cancer were analyzed. Gender: Male 17 (81%)/Female 4 (19%); Median age [range]: 62 [49-84]; Primary Tumor site: Right colon 4 (19%)/ Left colon 11 (52%)/Rectum 6 (29%); Embryologic origin: Midgut 4 (19%)/Hindgut 17 (81%); Histologic grade: Low 18 (86%)/High 3 (14%); Stage: II 1 (5%)/III 6 (29%); IV 14 (67%); KRAS mutational status: Wild-Type 13 (62%)/Mutated 8 (38%). Ten patients (48%) had liver limited disease. For SHH and for SMO, one different patient each had non-evaluable stain and therefore results of are based on 20 patients for both immunohistochemical assessments. Intensity of stain was evaluated using a semiquantitative scoring system. All 20 patients had positive stain for SHH. Results of semiquantitative scoring system for SHH expression were: + 3 (14%)/ ++ 10 (48%)/ + ++ 7 (33%). All 20 patients had positive stain for SMO. Results of semiquantitative scoring system for SMO expression were: + 3 (14%)/ ++ 10 (48%)/ + ++ 7 (33%). Correlation between expression of SHH and SMO: 12 out of 19 tumors showed stain of both SHH and SMO with the same intensity +, ++ or +++. Median age of patients with SHH+ was lower than that of patients with SHH ++ and SHH + ++ (62 versus 72 years; Student-Fisher P = 0.04). Patients with SMO + ++ had liver limited disease more frequently than patients with SMO+ and SMO ++ (Chi-square/Fisher-exact-test P= 0.023). No other relationship was found between SHH or SMO expression and other clinicopathological factors such as KRAS mutational status, embryologic origin or stage.

Conclusion

In this study all samples from metastatic colorectal cancer patients expressed both SHH and SMO. Patients with strong SMO expression showed a higher probability of having liver limited disease whereas patients with weak SHH expression were younger than patients with strong SHH expression. These results deserve further investigation in larger confirmatory studies.