Person:

Mashimo, Hiroshi

In Western countries, distal esophageal adenocarcinoma has outnumbered squamous cell carcinoma because of a dramatic increase in the prevalence of columnar-lined esophagus. Because the relative prevalence of these diseases remains unknown in China, we investigated the histopathology of distal esophageal neoplasm in resection specimens from a high-volume medical center in China. A computerized search of esophageal cancer was conducted in the pathology database between 2004 and 2010. Cancers with epicenter located within 5 cm above the gastroesophageal junction were retained for analysis. Pathology reports were reviewed along with medical, radiologic, and endoscopic records. All histology slides of selected cases were reevaluated (median, 13 per case). Conventional and basaloid squamous cell, adenosquamous, mucoepidermoid, and neuroendocrine carcinomas and esophageal adenocarcinoma were categorized according to the World Health Organization classification of esophageal cancers. The presence of columnar-lined esophagus and other pathologic changes were assessed in cases with residual esophageal mucosa. Among 1101 resections, 204 (19%) qualified for the study. Conventional and basaloid squamous cell, adenosquamous, mucoepidermoid, and neuroendocrine carcinomas and esophageal adenocarcinoma represented 76%, 11%, 3%, 2%, 6%, and 1% of the cases, respectively. Synchronous carcinomas were found in 12% and consisted of primarily squamous cell carcinoma (50%) and proximal gastric adenocarcinoma (38%). Columnar-lined esophagus was detected in 18% of the cases, among which intestinal metaplasia was present in 30% and low-grade dysplasia in 7%. In conclusion, distal esophageal carcinomas in Chinese patients showed a wide histopathologic spectrum with predominant squamous cell carcinoma and rare esophageal adenocarcinoma. Although common, columnar-lined esophagus appears pathogenetically insignificant for most distal esophageal carcinomas.

Lgr5 has recently been identified as a murine marker of intestinal stem cells. Its expression has not been well characterized in human gastrointestinal tissues, but has been reported in certain cancers. With the increasing appreciation for the role of cancer stem cells or tumor-initiating cells in certain tumors, we sought to explore the expression of Lgr5 in normal and premalignant human gastrointestinal tissues. Using standard immunostaining, we compared expression of Lgr5 in normal colon and small intestine vs. small intestinal and colonic adenomas and Barrett's esophagus. In the normal tissue, Lgr5 was expressed in the expected stem cell niche, at the base of crypts, as seen in mice. However, in premalignant lesions, Lgr5+ cells were not restricted to the crypt base. Additionally, their overall numbers were increased. In colonic adenomas, Lgr5+ cells were commonly found clustered at the luminal surface and rarely at the crypt base. Finally, we compared immunostaining of Lgr5 with that of CD133, a previously characterized marker for tumor-initiating cells in colon cancer, and found that they identified distinct subpopulations of cells that were in close proximity, but did not costain. Our findings suggest that (1) Lgr5 is a potential marker of intestinal stem cells in humans and (2) loss of restriction to the stem cell niche is an early event in the premalignant transformation of stem cells and may play a role in carcinogenesis.