Barrett's esophagus is diagnosed when goblet cells are found in the lower esophageal mucosa. However, the distribution of these cells is patchy and they may not represent the earliest marker of intestinal metaplasia. Cdx2 is a transcription factor whose expression in normal tissues is restricted to intestinal-type epithelium. Its distribution in the columnar-lined esophagus with and without intestinal metaplasia has been seldom studied. We evaluated Cdx2 expression in lower esophageal biopsies from 90 patients with endoscopic diagnosis of short segment Barrett's esophagus, including 45 consecutive cases showing intestinal metaplasia (goblet cells present in hematoxylin eosin and/or Alcian blue stains) and 45 consecutive cases without goblet cells. 25 samples of cardiac-type mucosa without intestinal metaplasia biopsied from the stomach served as controls. All cases with intestinal metaplasia revealed Cdx2 reactivity in goblet cells and adjacent nongoblet columnar cells. Dysplastic foci, seen in five cases from this group, were Cdx2 positive. In the group without goblet cells, Cdx2 was focally expressed by columnar cells in 17 (38%) cases. All control cases were Cdx2 negative. Strips of Alcian blue-positive nongoblet columnar cells ('columnar blues') were observed in 11 (24%) of the cases without intestinal metaplasia. All these foci were Cdx2 negative. In conclusion, Cdx2 is a highly sensitive marker for Barrett's esophagus. It is also expressed in a significant minority of cases of columnar-lined esophagus without goblet cells, suggesting that it may detect intestinal phenotypic modifications in the absence of goblet cells. Accordingly, Cdx2 immunostaining could help identify patients with Barrett's metaplasia in cases where no goblet cells are visible in biopsies from the columnar-lined esophagus. Finally, lack of Cdx2 expression in the 'columnar blues' suggests that these cells are not diagnostic of intestinal metaplasia.
Histologic differentiation of primary ovarian carcinoma from colonic carcinoma metastatic to the ovary may be difficult. Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunostaining is usually used, but these markers lack specificity for ovarian and intestinal epithelium, and overlapping results have been reported. Cdx2 is a transcription factor whose expression in normal tissues is limited to the intestinal epithelium. It is also expressed in the vast majority of colonic carcinomas and in a sizeable proportion of cases of gastric, pancreatobiliary, and ovarian mucinous carcinomas. We evaluated Cdx2, CK7, and CK20 expression in 50 ovarian carcinomas (15 serous, 20 mucinous, and 15 endometrioid), 15 colonic carcinomas metastatic to the ovaries, and 20 primary colonic carcinomas. The extent (1-25%/1+, 26-75%/2+, >75%/3+) and intensity (weak/1+, strong/2+) of staining were recorded semiquantitatively. All primary and metastatic colonic carcinomas had diffuse (3+) strong Cdx2 reactivity. All serous and endometrioid tumors were Cdx2 negative, whereas mucinous carcinomas had 1+ or 2+ immunoreactivity. All ovarian carcinomas had strong diffuse CK7 staining, whereas all colonic carcinomas were negative for CK7. CK20 stained diffusely and strongly all primary and metastatic colonic carcinomas and was 1+ or 2+ in all mucinous carcinomas, in 67% of serous carcinomas, and in 33% of endometrioid carcinomas. In conclusion, 1) Cdx2 is a highly sensitive (100%) marker for colonic carcinoma metastatic to the ovary; 2) Cdx2 is more specific than CK20 as it is not expressed by serous and endometrioid carcinomas; and 3) a limited panel of Cdx2 and CK7 helps in distinguishing colonic carcinomas metastatic to the ovaries (Cdx2+/CK7-) from primary ovarian serous (Cdx2-/CK7+), endometrioid (Cdx2-/CK7+), and mucinous (Cdx2+/CK7+) carcinomas.
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