title: Lack of PTEN expression in endometrial intraepithelial neoplasia is correlated with cancer progression.
abstract: We tested the hypothesis that PTEN inactivation may stratify cancer progression risk among putative endometrial hyperplasias, classified prognostically by means of the morphometric D score (DS). The DS, calculated from 3 morphometric variables measured in routine hematoxylin-eosin-stained endometrial biopsy slides, is the most sensitive and specific method of endometrial cancer risk prediction currently available. Clinical outcomes of 103 women with endometrial hyperplasia on biopsy were tallied according to the DS. Seven (7/103; 7%) patients with carcinoma during follow-up were all distributed within the high-risk prognostic group (ie, DS <1 = endometrial intraepithelial neoplasia [EIN]) (7/21; 33% progression). None of the 82 cases with a DS higher than 1 progressed. All cases that progressed were PTEN null, indicating that this genotype is capable of further stratifying cancer progression risk in hyperplasias irrespective of histological categorization. However, only 16% of the PTEN-null cases progressed. When PTEN expression pattern was combined with EIN, the prognostic power was greatly increased (specificity from 63% for PTEN and 85% for EIN to 93% when combined; positive predictive value from 16% and 33% to 50%). We conclude that loss of PTEN expression is the first biomarker in EIN that increases the accuracy of the prognostic DS to predict cancer progression risk. Unless endometrial hyperplasias are stratified by histological morphometric D-Score, PTEN has a low positive predictive value.
authors.affiliation: Department of Pathology, Stavanger University Hospital, Norway. baja@sir.no
authors.forename: Jan Pieter Albert
authors.initials: JP
authors.lastname: Baak
authors.forename: Bianca
authors.initials: B
authors.lastname: Van Diermen
authors.forename: Anita
authors.initials: A
authors.lastname: Steinbakk
authors.forename: Emiel
authors.initials: E
authors.lastname: Janssen
authors.forename: Ivar
authors.initials: I
authors.lastname: Skaland
authors.forename: George L
authors.initials: GL
authors.lastname: Mutter
authors.forename: Bent
authors.initials: B
authors.lastname: Fiane
authors.forename: Kjell
authors.initials: K
authors.lastname: Løvslett
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D004714:Endometrial Hyperplasia / Q000473:pathology*; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008875:Middle Aged; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis*; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human