Nada Hamzah Shareef Al-Shabbani1 and Iqbal Abed Fahad 2

1Department of Pathology, College of Medicine, University of Wasit, Al-Kut, Iraq
2Department of obstetrics and gynecology College of Medicine University of Wasit Iraq

Abstract

Background: Endometrial adenocarcinoma is among the most common gynecologic cancers in the world
and with rising incidence which can be attributed to obesity, type 2 diabetes mellitus and lifetime exposure
to unopposed estrogen. Traditional prognostic factors (histological grade and FIGO stage) are not
sufficient to describe the molecular heterogeneity of this tumor. Ki-67 is a nuclear proliferation biomarker
expressed at all active cell-cycle phases and PTEN is the most commonly inactivated tumor suppressor in
endometrioid carcinoma, whose joint evaluation could provide better prognostic stratification.
Objective: To examine the Ki-67 and PTEN immunohistochemistry in endometrial adenocarcinoma,
correlate the expression of both biomarkers with histological grade and test the statistical correlation
between the two biomarkers as composite prognostic factors.
Materials and Methods: The data was analyzed in terms of grading (by hematoxylin and eosin (H&E)
staining) according to WHO 2020s classification and immunohistochemistry (Ki-67 (labeling index
scored 0 to 4+, measured in 5 high-power fields) and PTEN (immunoreactive score 0 to 9: absent, low,
moderate, or high) of 50 formalin-fixed paraffin-embedded (FFPE) endometrial adenocarc Chi-square test
and Spearman rank correlation coefficient (significance level: p < 0.05) were used to evaluate the
statistical associations.
Results: The high level of Ki-67 (>51%), moderate level (12), and low level of Ki-67 (8) were observed
in 30 cases (60%), 12 cases, and 8 cases respectively. In 25 cases (50%), PTEN was absent altogether
(25); in 15 cases (30%), it was low, in 8 cases (16%), it was moderate, and in 2 cases only (4%), it was
high. Cross-tabulation showed that complete PTEN loss was seen in 66.7% of high-Ki-67. An important
negative correlation was established between the two markers ( 2 = 17.91, 6df = 6, p = 0.0065; Spearman
0467, p = 0.0006).
Conclusion: Ki-67 and PTEN are valid and complementary immunohistochemical biomarkers to use in
assessing tumor aggressiveness in endometrial adenocarcinoma. Their high negative correlation is an
indicator of PI3K/AKT/mTOR pathways deregulation as a result of PTEN loss. Combined assessment
enhances prognostic risk stratification, contributes to the targeted making of therapeutic decisions, and
should be validated by using larger multicenter prospective studies.

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