Standardized AgNOR analysis as a prognostic parameter in endometrial carcinoma, endometrioid type.
OBJECTIVE
To evaluate interobserver reproducibility of histologic grade in endometrial adenocarcinomas of endometrioid type (EC), to assess the relationships between nuclear grade and the amount of argyrophilic nucleolar organizer region (AgNOR) proteins and to determine the prognostic value of AgNOR proteins and the main clinicopathologic parameters.


METHODS
Architectural and nuclear grading were independently assessed by two pathologists in 64 formalin-fixed, paraffin-embedded surgical samples of EC obtained from an equal number of patients (age range, 38-84 years; mean, 63.5). Interobserver agreement was determined using the kappa statistic; discrepant cases were reviewed, and a consensus was reached. Standardized AgNOR analysis was performed according to the guidelines of the Committee on AgNOR Quantification, measuring the mean area of AgNORs per nucleus (NORA) by an image analysis system.


RESULTS
The kappa values for interobserver agreement were substantial for architectural grading and moderate for nuclear grading. When NORA values were compared to the nuclear grade assessed by different observers, the most significant linear correlation (r = .713, P < .001) was found for the nuclear assessment obtained by consensus of the two pathologists. Moreover, statistical analysis allowed discrimination of architectural grade 1 from grade 2 and 3 EC. By the Kaplan-Meier method, the prognosis was worse for patients with higher NORA values (> 4.212 micron 2), while, by Cox multivariate analysis, AgNOR quantity emerged as an independent prognostic variable.


CONCLUSIONS
Use of standardized AgNOR analysis may be an additional and objective tool in the assessment of histologic grade as well as a reliable method of determining prognosis in EC.
Department of Human Pathology, University of Messina, Messina, Italy.
G
G
Giuffrè
E
E
Fulcheri
M
M
Gualco
F
F
Fedele
G
G
Tuccari
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000648:ultrastructure; D000328:Adult; D016889:Endometrial Neoplasms / Q000401:mortality / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D008875:Middle Aged; D009697:Nucleolus Organizer Region / Q000473:pathology*; D015588:Observer Variation; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016622:Silver Staining; D016019:Survival Analysis