الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Endometrial carcinoma (EC) is the most common cancer of the female reproductive organs
in the developed world and a major cause of both morbidity and mortality. EC was diagnosed in
417,367 women in 2020, world-wide, with the highest disease burden in North America and
Western Europe. The incidence of EC is rapidly increasing. Accounting for the majority of uterine
corpus cancers, it is important to promptly diagnose endometrial carcinoma and differentiate
between the different types for proper management.
P16 is a tumor suppressor gene encoded by CDKN2A gene located on (9p21.3). It is
known as INK4a (inhibitor of cyclin-dependent kinase 4a). It inhibits cell growth and suppresses
tumor progression. It encodes proteins that regulate a cell cycle important pathway, which is the
retinoblastoma (Rb) pathway. Using both HPV dependent and independent mechanisms,
increased expression of p16 can be detected by immunohistochemistry in many tumors, such as
cervical cancer, Hodgkin and non-Hodgkin lymphomas, gastric adenocarcinomas, lung
adenocarcinomas, liposarcomas, neuroendocrine carcinomas and a subset of uterine carcinomas.
Beta-catenin, a protein encoded by CTNNB1 gene located on 3p22.1, regulates cell to cell
adhesion and the transcription of genes. Beta-catenin has the master role in Wnt signaling
pathway whose dysregulation is incriminated in the development of many solid tumors and
hematological malignancies.
The aim of this work is to study the immunohistochemical expression of p16 and betacatenin
in endometrial carcinoma types I and II and its correlation with clinicopathological
parameters (age, grade, tumor stage from hysterectomy specimens, lymphovascular invasion and
necrosis).
The present work was undertaken on 60 cases of endometrial carcinoma (EC) obtained from
32 cases (53.33%) surgically resected total abdominal hysterectomy (TAH) specimens and 28
cases (46.66%) from Dilatation and Curettage (D&C) specimens received at the Pathology
Department, Alexandria University, Medical Research Institute.
In the current work, there was histopathological examination to assess endometrial
carcinoma types, grade, stage, lymphovascular invasion and necrosis. Also, there was
immunohistochemical staining for p16 and beta-catenin.
In the current work, the 60 cases included 13 cases (21.7%) were < 50 years and the
remaining 47 (78.3%) were ≥ 50 years. Forty-one cases (68.3%) were type I endometrioid
carcinoma and 19 cases (31.7%) were type II endometrial carcinoma, comprising of 15 cases
serous subtype, 2 cases clear cell subtype and 2 cases carcinosarcoma (malignant mixed
Mullerian tumor, MMT). Of the 60 studied cases, 11 cases (18.3%) were FIGO grade 1, 25 cases
(41.7%) were FIGO grade 2, 24 cases (40%) were FIGO grade 3. Ten cases (16.7%) were FIGO
stage 1a,10 cases (16.7%) were stage 1b, 3 cases (5%) were stage 2, 9 cases (15%) were stage
3a. Twenty-eight cases (46.7%) were D&C biopsies with no available follow up data. Nine cases
(15%) were negative for lymphovascular invasion, 23 cases (38.8%) were positive for
lymphovascular invasion. Twenty-eight cases (46.7%) were D&C biopsies where
Summary, Conclusions & Recommendations
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lymphovascular invasion could not be assessed thoroughly. Necrosis was absent in 53 cases
(88.3%), while it was identified in 7 cases (11.7%).
In the present study, there was a positive significant correlation between p16 and the
following parameters: histological type of EC (p=0.003) and FIGO grade(p=0.013).
There was no significant correlation between p16 and the following parameters: age of the
cases (P=0.056), FIGO stage(p=0.255), lymphovascular invasion (p= 0.642) or necrosis
(p=0.070).
In type I and II EC, there was no significant correlation between p16 and any
clinicopathological parameters.
In the current study, there was a positive significant correlation between beta-catenin and the
following parameters: histological type of EC (p=0.018) and FIGO stage (p=0.041).
There was no significant correlation between beta-catenin and the following parameters:
age of the cases (p=0.387), FIGO grade (p=0.082), lymphovascular invasion (p=0.122) or
necrosis (p=0.454).
In type I and II EC, there was no significant correlation between beta-catenin and any
clinicopathological parameters.
In the present study, there was a positive inverse correlation between p16 and beta-catenin
in endometrial carcinoma (p=0.033) and in type I EC (p=<0.001*) but not in type II EC
(p=0.309).
Therefore, from the present study we concluded that, positive expression of p16 and betacatenin
is correlated with endometrial carcinoma histological type (type II in the former and type
I in the latter), high FIGO grade (regarding p16) and lower FIGO stage (regarding beta-catenin).