title: Morules in endometrial carcinoma and benign endometrial lesions differ from squamous differentiation tissue and are not infected with human papillomavirus.
abstract: BACKGROUND
  Squamous differentiation/squamous metaplasia is often associated with endometrial adenocarcinoma and benign lesions, such as endometrial hyperplasia and chronic endometritis. Morules have distinct histological characteristics, and are referred to as squamous metaplasia or squamoid metaplasia.
  
  
  OBJECTIVE
  To focus on the histological characteristics of morules and clarify the difference between morules and squamous differentiation.
  
  
  METHODS
  Twenty endometrioid carcinomas with morules or squamous differentiation, five adenosquamous carcinomas, and eight non-carcinomatous endometrial lesions with morules were investigated. Numerous antibodies for epithelial membrane antigen (EMA), involucrin, cytokeratins, neuropeptides, and oncofetal antigens were used for immunohistochemistry. In situ hybridisation and polymerase chain reaction were used to detect human papillomavirus (HPV).
  
  
  RESULTS
  The morules observed were uniform cell clusters, with no squamous differentiation. They were immunonegative for epithelial antigens including involucrin, EMA, and cytokeratins, but were positive for neurone specific enolase. A few morules were immunopositive for acetylcholine esterase, and one case was positive for somatostatin; neither oncofetal nor proliferative cell markers, including blood group A, B, and AB, or other neuropeptides were demonstrated in the morules. HPV DNA was not found in either the morules in the carcinomas or in the benign lesions. However, true squamous differentiation tissue in four endometrioid carcinomas and two adenosquamous carcinomas was HPV positive using in situ hybridisation.
  
  
  CONCLUSIONS
  Morules are histologically distinct from squamous metaplasia/squamous differentiation tissue. Morules are thought to be neuroectodermal-like cell clusters, and are not infected with HPV. In contrast, some of the true squamous differentiation tissue was associated with HPV infection.
authors.affiliation: Division of Pathology and Cell Biology, Graduate School and Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. cellpath@med.u-ryukyu.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Chinen
authors.forename: K
authors.initials: K
authors.lastname: Kamiyama
authors.forename: T
authors.initials: T
authors.lastname: Kinjo
authors.forename: A
authors.initials: A
authors.lastname: Arasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Ihama
authors.forename: T
authors.initials: T
authors.lastname: Hamada
authors.forename: T
authors.initials: T
authors.lastname: Iwamasa
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000821:virology; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000821:virology; D003598:Cytoskeletal Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis; D016889:Endometrial Neoplasms / Q000473:pathology* / Q000821:virology; D004717:Endometrium / Q000473:pathology* / Q000821:virology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008679:Metaplasia; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D015534:Trans-Activators / Q000235:genetics; D011503:Transglutaminases / Q000235:genetics; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004279:DNA, Viral; D011498:Protein Precursors; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin; C032253:involucrin; D011503:Transglutaminases; C105804:transglutaminase 1