Chemoradiotherapy-induced Changes in Mucinous Components in Rectal Cancer Tissue: Evaluation on High Iron Diamine-alcian Blue and Mucin 1 Staining

Abstract

Abstract. Background Total mesorectal excision (TME) after neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for rectal cancer (1-4). Patients with mucinous carcinoma have been reported to have a poor response to nCRT, as well as poor outcomes. In some patients, however, nCRT may induce the formation of mucin lakes (MLs) in rectal cancer tissue (5-12). The ability to determine whether MLs are induced or originally exist in resected specimens would be of great clinical significance.Sialomucin and sulphomucin are included in intracytoplasmic mucin of cancer cells and MLs in patients with colorectal cancer and can be identified by high iron diamine-Alcian blue (HID-AB) staining (13). Mucin 1 (MUC1), a transmembrane mucin and a membrane-bound glycoprotein, exists in cancer cells and in MLs in colorectal cancer tissue and has been reported to be related to outcomes (14-17).HID-AB staining and MUC1 immunohistochemical staining was, therefore, performed in resected specimens of rectal cancer obtained from patients who received nCRT and those who did not, to evaluate mucinous components in cancer cells and MLs in cancer tissue and examine whether nCRT induces changes in mucinous components. Patients and MethodsSubjects. From 2005 through 2015, a total of 293 patients with rectal cancer underwent curative surgery. Among the 205 patients who received nCRT, the ML formation which occupied at least 20% of the area of the maximum cut surface of the resected specimens was found in 20 patients. These patients were designated as the CRT-MC group. Among the 88 patients who did not receive CRT, 9 patients were histologically diagnosed with mucinous carcinoma on the resected specimens in which ML formation was remarkable (non-CRT-MC group), and 18 patients were diagnosed with well-or moderately differentiated adenocarcinoma but had apparent ML formation in less than 50% of the area ratios of the tumors. These patients were designated as the non-CRT-AC group. A total of 47 patients were studied. This study was approved by the institutional review board of our University (17R-238), and all patients gave their written informed consent.HID-AB staining, MUC1 staining, and evaluations. To perform HID-AB staining, the sections were deparaffinized and then stained with HID solution, prepared using N, N-dimethyl-m-phenylenediamine dihydrochloride (120 mg) and N,N-dimethyl-p-phenylenediamine 4783