Cell kinetics analysis in stage I endometrial carcinoma as determined by image cytometry and immunohistochemistry. Correlation with clinicopathologic characteristics.
OBJECTIVE
To test the significance of various proliferative indices in endometrial carcinoma (EC) since previous investigations failed to yield consistent results that would establish them as factors of clinical importance.


METHODS
Seventy patients with EC were evaluated for various proliferative indices (mitotic index, Ki-67 index, argyrophilic nucleolar organizer (AgNOR) number and area per nucleus, and p53 protein expression) in relation to image cytometry (nuclear area, diameter and roundness) and standard clinicopathologic features (age, histologic type and grade, and depth of invasion). We also tested the proliferation index (PI), which combines the Ki-67 index and AgNOR area in Ki-67-positive nuclei. Slides from each case were double stained for Ki-67 antigen and AgNOR proteins for this purpose.


RESULTS
Mitotic counts were significantly higher in papillary-serous (vs. endometrioid) tumors (P = .0001), high grade (vs. low grade) tumors (P = .0001), deeply invasive (P = .017) and p53-positive tumors (P = .017). AgNOR counts correlated only with age (higher in older women, P = .002), while the PI correlated with mitotic counts (P = 0.28) and marginally with depth of invasion (P = .06). Morphometric variables were associated just with histologic type and grade. p53 Protein was expressed exclusively in invasive tumors and was related strongly to histologic type (P = .0029) and grade (P = .0001).


CONCLUSIONS
Our data reestablish the value of classic histopathologic features (mitotic index, histologic type and grade) as the most important tools for EC evaluation. In addition, we suggest that p53 immunostaining may be used for predicting aggressive behavior in EC.
Miliaras
Dimosthenis
D
Department of Pathology, General Clinic, and Laboratory of Histology and Embryology, Medical Faculty, Aristotle University of Thessaloniki, Thessaloniki, Greece. miliaras@auth.gr
Papaemmanuil
Styliani
S
D000367:Age Factors; D014408:Biomarkers, Tumor / Q000032:analysis; D002455:Cell Division; D002467:Cell Nucleus / Q000473:pathology; D003627:Data Interpretation, Statistical; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D019044:Image Cytometry / Q000379:methods*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D007700:Kinetics; D008875:Middle Aged; D008940:Mitotic Index; D009361:Neoplasm Invasiveness / Q000175:diagnosis; D009367:Neoplasm Staging; D009697:Nucleolus Organizer Region / Q000473:pathology; D016622:Silver Staining; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53