Computerized Image Analysis of p53 and Proliferating Cell Nuclear Antigen Expression in Benign, Hyperplastic, and Malignant Endometrium

Abstract

Context.—The endometrium is an intrinsically dynamic tissue with great capability for regeneration and proliferation; consequently, there is some overlap between features seen in benign, premalignant, and malignant lesions. This leads to marked intrabiopsy, interbiopsy, and interobserver variability. Objective.—We studied the specificity and sensitivity of computerized image analysis of molecular markers to evaluate its potential use as a diagnostic tool. Design.—Specimens from 100 patients were examined and the following histologic diagnoses were assigned: proliferative endometrium (n = 10), secretory endometrium (n = 10), endometrial hyperplasia (n = 40; 30 with no atypia, 10 with atypia), and carcinoma (n = 40; 20 endometrioid, 10 serous, and 10 clear cell). All cases were evaluated immunohistochemically for p53 and proliferating cell nuclear antigen (PCNA) expression. Computerized image analysis was performed with a CAS 200 digital analyzer. Results.—Expression of p53 was found only in carcinomas (65%) and endometrial hyperplasia with atypia (30%). Expression of p53 was higher in the poor prognostic categories (serous carcinoma and clear cell carcinoma) than in endometrioid carcinoma. In endometrioid carcinoma, p53 expression correlated with grade. Proliferating cell nuclear antigen showed a similar pattern of results to p53 in the various carcinoma subtypes and endometrioid carcinoma grades. Endometrial hyperplasia PCNA values were the lowest among all the groups. Both carcinomas and proliferative endometrium showed higher glandular and stromal PCNA values, significantly different from endometrial hyperplasia with atypia. In proliferative endometrium, stromal PCNA was the highest among all of the groups. The p53 and PCNA results correlated with each other for carcinoma. Conclusions.—Computerized image analysis correlates well with the established morphologic groups of endometrial pathology and yields results consistent with previous studies. Owing to its higher degree of sensitivity, computerized image analysis is of potential use in cases of diagnostic dilemmas and can help objectively allocate the case in the correct category (eg, proliferative endometrium vs endometrial hyperplasia, endometrial hyperplasia with atypia vs endometrioid carcinoma). It is particularly useful in the evaluation of stromal changes.

P53 Expression in Endometrial Hyperplasia and Endometrial Carcinoma

“…In the current study, none of the normal endometrium, simple hyperplasia, and complex hyperplasia without atypia showed any positivity for p53. These negative results were also reported by Elhafey et al, 18 and Sakuragi et al, 19 . P53 immuno positivity was observed in 2 out of 10 cases (20%) of atypical endometrial hyperplasia, Figure (1).…”

“…P53 immuno positivity was observed in 2 out of 10 cases (20%) of atypical endometrial hyperplasia, Figure (1). Elhafey et al 18 found immuno positivity in 3 of 10 cases (30%) of atypical endometrial hyperplasia, while Sakuragi et al 19 found no p53 immuno positivity in 3 cases (100%) of atypical endometrial hyperplasia. This variability can be explained by the small sample size of atypical endometrial hyperplasia.…”

p53, estrogen and progesterone receptors in diagnostic curettage for endometrial adenocarcinoma and their correlation with morphological data and disease stage at hysterectomy

“…23 We were able to confirm that p53 expression is inversely related to that of estrogen and progesterone receptors, thus indicating a dual theory of carcinogenesis in the endometrium. 11,[23][24][25][26] Expression of the markers studied was not significantly associated with the disease stage. It has been reported that p53 expression correlates with more advanced stages.…”

Immunohistochemical expression of PARP-1 in triple-negative endometrial cancer – a comparison of different score systems

“…Thanks to the use of this type of software, it was possible to evaluate each preparation according to the same criteria. Digital image analysis has already been used in endometrial cancer research [27][28][29]. Besides the evaluation of the receptor expression itself, it is possible to evaluate the surface area, optical density, or the shape of the cell nuclei.…”