Clinicopathological and Prognostic Evaluations of Mixed Adenoneuroendocrine Carcinoma of the Colon and Rectum: A Case-Matched Study

BACKGROUND: Mixed adenoneuroendocrine carcinoma of the colon and rectum is a very rare type of tumor. OBJECTIVE: The aim of the present study was to evaluate the clinicopathological characteristics and prognosis of mixed adenoneuroendocrine carcinomas of the colon and rectum. DESIGN: This was a retrospective case-matched analysis (from March 2007 to December 2013). SETTINGS: This study was conducted at Yokosuka Kyosai Hospital. PATIENTS: One thousand three hundred six consecutive patients with a preoperative diagnosis of colorectal cancer and who underwent tumor resection were enrolled in the present study. Each patient diagnosed with mixed adenoneuroendocrine carcinoma was 1:2 matched with 2 counterparts who had been diagnosed with adenocarcinoma. INTERVENTION: Immunohistochemical staining for neuroendocrine markers (chromogranin A, synaptophysin, and CD56) was performed. Cases in which the neuroendocrine component accounted for >30% of the tumor were diagnosed as mixed adenoneuroendocrine carcinomas. RESULTS: Among 1306 patients, 42 patients (3.2%) were diagnosed with mixed adenoneuroendocrine carcinoma and were compared with 84 patients with adenocarcinoma who had been randomly case matched. The average Ki-67-labeling index value was 78.0% (range, 30.0%-99.0%). Chromogranin A, synaptophysin, and CD56 positivity were observed in 42.9% (18/42), 81.0% (34/42), and 33.3% (14/42) of the tumors. Both the disease-free survival and overall survival were significantly worse for mixed adenoneuroendocrine carcinoma than for adenocarcinoma. Ten patients underwent treatment with oxaliplatin-based chemotherapy. The response rate was 40.0%; the median progression-free survival and overall survival were 6.3 months and 18.1 months. LIMITATIONS: This was a retrospective single-institution study that included a limited number of cases. The treatment regimens used included different types of oxaliplatin-based chemotherapy. CONCLUSION: Mixed adenoneuroendocrine carcinoma of the colon and rectum has a poor prognosis after curative resection and should be distinguished from adenocarcinoma.