Prognostic significance of CDX2 and mucin expression in small intestinal adenocarcinoma

Abstract

The clinicopathological and prognostic significance of CDX2 and mucin expression have not been comprehensively evaluated in small intestinal adenocarcinoma. Immunohistochemical microarray analyses of CDX2, MUC1, MUC5AC, and MUC6 protein expressions in 189 surgically resected small intestinal adenocarcinoma cases were examined and compared with various clinicopathologic variables, including survival. CDX2, MUC1, MUC5AC, and MUC6 expressions were observed in 43.4% (82 patients), 37.6% (71), 31.7% (60), and 21.7% (41) of patients, respectively. Whereas CDX2 expression was found to be associated with lowgrade tumors (P ¼ 0.034), fewer nodal metastases (P ¼ 0.019), and less perineural invasion (P ¼ 0.049) in small intestinal adenocarcinoma patients, patients expressing MUC1 tended to demonstrate high-grade (P ¼ 0.021) and nodular or infiltrative (P ¼ 0.020) tumors. On the basis of the combined CDX2, MUC1, MUC5AC, and MUC6 expression patterns, small intestinal adenocarcinoma patients were further classified as intestinalAmong these immunophenotypes, intestinal-type patients demonstrated more frequent distal (jejunal or ileal; P ¼ 0.033), tubular (P ¼ 0.039), and low-grade tumors (P ¼ 0.004) and significantly better survival according to univariate (Po0.0001) and multivariate (P ¼ 0.001) analyses. In summary, intestinal immunophenotype adenocarcinomas are associated with distal (jejunal or ileal), tubular, and low-grade tumors and better survival outcomes. Hence, CDX2 and mucin immunohistochemical staining may provide better estimations of survival after surgical resection and intestinal immunophenotype could therefore be used as a better prognostic indicator of small intestinal adenocarcinoma. Modern Pathology (2014Pathology ( ) 27, 1364Pathology ( -1374 doi:10.1038/modpathol.2014 published online 7 March 2014 Keywords: adenocarcinoma; CDX2; immunohistochemistry; mucin; prognosis; small intestine Primary small intestinal adenocarcinomas account for only 5% of malignant neoplasms in the gastrointestinal tract despite the long length of the small intestine and the significant mucosal coverage over the entire gastrointestinal tract. 1 In 2013, it is estimated that 8810 Americans will be diagnosed with small intestinal adenocarcinoma. 1 Despite recent improvements in the detection of the small intestinal adenocarcinomas, including improved imaging techniques and endoscopic modalities, the diagnosis of small intestinal adenocarcinomas is usually made at an advanced clinical stage and the 5-year survival rate is only 41.2%. 2 Several clinicopathologic factors, including lymph node metastasis and the distal locations of these tumors (jejunum and ileum), are known as the most important independent prognostic factors. 2 Although several molecular alterations, including KRAS, TP53, and DPC4/SMAD4 mutations and the overexpression of cyclinD1, are known to be involved in small intestinal adenocarcinoma carcinogenesis, [3][4][5][6]

Lynch syndrome-related small intestinal adenocarcinomas

“…In our previous cohort study of 197 patients with SIAC, we identified 31 patients (16%) with synchronous or metachronous malignant tumors, including 13 colorectal carcinomas and 10 gastric cancers [10, 11]. No patients with LS were initially identified in our previous report because of limited information regarding MMR immunohistochemistry and MSI tests at that time [10].…”

“…A total of 197 surgically resected primary SIAC cases were collected from the surgical pathology archives of 22 Korean institutions by the Korean Small Intestinal Cancer Study Group, as previously reported [11]. Carcinomas extending into the small bowel from the surrounding gastrointestinal tract organs, such as the stomach, ampulla of Vater, pancreas, cecum, or appendix, were excluded from analysis.…”

“…Clinicopathologic data, which were collected as part of a previous study [11], were updated and used in the present study. Family and clinical histories were investigated in detail through an electronic medical record and chart review.…”

Clinicopathologic and prognostic associations of KRAS and BRAF mutations in small intestinal adenocarcinoma

“…A total cohort of 197 surgically resected primary small intestinal adenocarcinoma cases was collected from the surgical pathology archives of 22 South Korean institutions by the Korean Small Intestinal Cancer Study Group, as previously reported. 21 Carcinomas extending from the surrounding gastrointestinal tract organs, such as the stomach, ampulla of Vater, pancreas, cecum or appendix, into the small bowel were excluded from the analysis. Clinical and pathologic data collected as part of a previous study were used again in this study.…”

“…Clinical and pathologic data collected as part of a previous study were used again in this study. 21 Histologic types and tumor grading were classified according to the WHO classification. 22 Briefly, tumor grading was classified as low-grade (well (495% with gland formation) and moderately differentiated (50-95% with gland formation) adenocarcinomas) and high-grade (poorly differentiated (1-49% with gland formation) and undifferentiated (no gland formation)) carcinomas.…”