ABSTRACT
BACKGROUND: Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors. MATERIAL AND METHODS: A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m2) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria. RESULTS: A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, p< 0.01 and p = 0.006, respectively). Thirty of the 32 biopsies co-expressing both markers had partial or absent tumor response (TRG 2-5), strengthening their positive predictive value (94%). The exclusive predictive role of YKL-40 and c-Met was confirmed using a multivariate analysis (p = 0.004 and p = 0.007 for YKL-40 and c-Met, respectively). TRG was the sole morphological parameter associated with poor outcome. CONCLUSION: c-Met and YKL-40 expression is a reliable predictor of partial/absent response to neoadjuvant CRT in rectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy.
Subject(s)
Adenocarcinoma/genetics , Adipokines/genetics , Biomarkers, Tumor/genetics , Gamma Rays/therapeutic use , Lectins/genetics , Proto-Oncogene Proteins c-met/genetics , Rectal Neoplasms/genetics , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Adipokines/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Biopsy , Capecitabine/administration & dosage , Chemoradiotherapy, Adjuvant/methods , Chitinase-3-Like Protein 1 , Drug Resistance, Neoplasm/genetics , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lectins/metabolism , Male , Middle Aged , Neoadjuvant Therapy/methods , Neoplasm Staging , Predictive Value of Tests , Prognosis , Proto-Oncogene Proteins c-met/metabolism , Rectal Neoplasms/diagnosis , Rectal Neoplasms/pathology , Rectal Neoplasms/therapyABSTRACT
PURPOSE: Pre- and post-treatment staging of anal cancer are often inaccurate. The role of positron emission tomograpy-computed tomography (PET-CT) in anal cancer is yet to be defined. The aim of the study was to compare PET-CT with CT scan, sentinel node biopsy results of inguinal lymph nodes, and anal biopsy results in staging and in follow-up of anal cancer. METHODS AND MATERIALS: Fifty-three consecutive patients diagnosed with anal cancer underwent PET-CT. Results were compared with computed tomography (CT), performed in 40 patients, and with sentinel node biopsy (SNB) (41 patients) at pretreatment workup. Early follow-up consisted of a digital rectal examination, an anoscopy, a PET-CT scan, and anal biopsies performed at 1 and 3 months after the end of treatment. Data sets were then compared. RESULTS: At pretreatment assessment, anal cancer was identified by PET-CT in 47 patients (88.7%) and by CT in 30 patients (75%). The detection rates rose to 97.9% with PET-CT and to 82.9% with CT (P=.042) when the 5 patients who had undergone surgery prior to this assessment and whose margins were positive at histological examination were censored. Perirectal and/or pelvic nodes were considered metastatic by PET-CT in 14 of 53 patients (26.4%) and by CT in 7 of 40 patients (17.5%). SNB was superior to both PET-CT and CT in detecting inguinal lymph nodes. PET-CT upstaged 37.5% of patients and downstaged 25% of patients. Radiation fields were changed in 12.6% of patients. PET-CT at 3 months was more accurate than PET-CT at 1 month in evaluating outcomes after chemoradiation therapy treatment: sensitivity was 100% vs 66.6%, and specificity was 97.4% vs 92.5%, respectively. Median follow-up was 20.3 months. CONCLUSIONS: In this series, PET-CT detected the primary tumor more often than CT. Staging of perirectal/pelvic or inguinal lymph nodes was better with PET-CT. SNB was more accurate in staging inguinal lymph nodes.
