High MUC2 Immunohistochemical Expression is a Predictor of Poor Response to Preoperative Radiochemotherapy (RCT) in Rectal Adenocarcinoma

Abstract

The purpose of this study is to establish if mucoid differentiation is associated with responsiveness to preoperative radiochemotherapy (RCT) in rectal adenocarcinomas. Thirty-two patients with rectal adenocarcinomas were preoperatively treated with 44 to 46 Gy in 22 to 23 fractions and with 5-fluorouracil (200 to 225 mg/m) before surgery. Mucoid differentiation was searched for both in pre-RCT biopsies with anti-MUC2 antiserum and in postoperative specimens. To evaluate the responsiveness to preoperative RCT, a regression grading was used (grades 0 to 4). Statistical analysis showed a significant negative correlation between immunohistochemical expression of MUC2 in pre-RCT biopsies and regression grade in postoperative specimens (r=-0.529; P=0.002). A significant cutoff value of 60% of MUC2 positive neoplastic cells in pre-RCT biopsies was observed (P=0.018): 13 cases with more than 60% exhibited a poor response to RCT (grade 0 in 5/13, grade 1 in 4/13, grade 2 in 4/13), whereas 19 cases with less than 60% showed a better response to RCT (grade 1 in 6/19, grade 2 in 9/19, grade 3 in 3/19, grade 4 in 1/19).

784 Clinical applications of molecular profiling of colorectal cancer

“…The ability to predict response to pretreatment chemoradiation may spare poorly responding patients from undergoing aggressive and severely toxic treatment [577,578] number [579]. Other molecules including P21 [63], EGFR [64], COX2 [580], MUC2 [529] and growth hormone receptor [581] were also examined as potential markers; nevertheless, it seems unlikely that they will prove to be clinically useful response predictors…”

“…Ambrosini-Spaltro et al investigated 32 pre-treatment biopsies by immunohistochemistry and determined MUC2 as a predictor of poor response [529]. Moreover, stromal CXCL12 and CXCR4 expression was found to be associated with recurrence and poor survival after neoadjuvant therapy in the 53 patients analysed using RQ-PCR and immunohistochemistry [528].…”