Immunohistochemical analysis of tumor regression grade for rectal cancer after neoadjuvant chemoradiotherapy

Abstract

e22089 Background: Tumor regression grade (TRG) as defined by Rodel et al. has been suggested as an independent prognostic factor for rectal carcinoma patients treated by preoperative chemoradiotherapy (CRT). However TRG 2 and 3 determination, semiquantitatively defined as more/less than 50% tumor regression, respectively, do not clearly correlate with prognosis. TRG 2 vs 3 discrimination is largely subjective hurdling prognostic analysis. The purpose of our study was to find an immunohistochemical pattern to better stratify these patients according to prognosis in term of disease free survival (DFS) and overall survival (OS). Methods: Immunohistochemistry of EGFR, VEGF, CD133, p53 and Ki67 was evaluated by tissue microarrays on surgical specimens from 88 patients. Preoperative chemotherapy was UFT-LV (30%) or oxaliplatin-based (70%) plus pelvic radiotherapy (50 Gy) followed by mesorectal excision. TRG was determined by the amount of viable tumor versus fibrosis, ranging from TRG 4 when no viable tumor cells were detected, to TRG 1 when regression was less than 25%. TRG 2 and 3 were defined as described above. Univariate analyses were performed according to the Kaplan-Meier method. Comparisons between curves were evaluated by the log-rank test. Cox regression was used for the multivariate analysis. Results: At a median follow-up of 39 months, the TRG was an independent predictor of DFS (p=0.05) and OS (p=0.001) but no differences were found between TRG 2 and 3 in terms of DFS (p=0.74) or OS (p=0.41). Our results show an immunohistochemical bad prognostic profile for tumors TRG 2 and 3 configured by double negativity of EGFR and CD133 expression (less than 5% of tumor cells membrane immunoreactivity for both antibodies). 3-year DFS and OS for these patients (vs. TRG 2 and 3 not-double negative) were 33 vs 65% (p=0.05) [HR=2.4 (95%CI, 0.9–6.1) p=0.06] and 77 vs 95% (p=0.06) [HR=4.1 (95%CI, 0.7–21.5) p=0.09]. Conclusions: The EGFR/CD133 double negative rectal tumors with TRG 2 or 3 after chemoradiotherapy show a higher risk of relapse or death. These results can help clinicians to determine better individual prognosis and are worth to confirm prospectively. No significant financial relationships to disclose.