Morules in endometrioid proliferations of the uterus and ovary consistently express the intestinal transcription factor CDX2

Abstract

To undertake an immunohistochemical analysis of squamous elements in endometrioid proliferations of the uterus and ovary and to compare the immunophenotype of typical squamous elements and so-called squamous morules. Cases of uterine or ovarian endometrioid glandular lesions with squamous elements were stained with CDX2, beta-catenin, oestrogen receptor (ER), CD10, p63 and high-molecular-weight cytokeratin LP34. Thirteen cases had typical squamous elements and 18 cases morules. Morules typically exhibited diffuse nuclear CDX2 and beta-catenin immunoreactivity and were positive for CD10 and LP34. They were usually ER- and p63-. In contrast, typical squamous elements were usually positive for ER, CD10, p63 and LP34. They were usually CDX2- or focally positive and exhibited no nuclear immunoreactivity for beta-catenin. Ten endometrioid carcinomas not exhibiting squamous differentiation were immunoreactive for CDX2; one was focally positive. Electron microscopy in two ovarian endometrioid adenocarcinomas with extensive morular differentiation showed that the morules exhibited epithelial features, but no overt evidence of squamous differentiation. Typical squamous elements and morules have an overlapping but differing immunophenotype. Morules exhibit no firm immunohistochemical or ultrastructural evidence of squamous differentiation, although immature squamous differentiation cannot be excluded. Nuclear beta-catenin positivity is in keeping with the observation that endometrioid glandular lesions with morules are often associated with beta-catenin gene mutation. The explanation for diffuse nuclear positivity with the intestinal transcription factor CDX2 in morules is not clear, but may be a result of overexpression of nuclear beta-catenin. We suggest that the term morular metaplasia is used instead of squamous morules.