الفهرس 
TitleOnly 14 pages are availabe for public view
 |  | from | 90 |  |  |
| | | from | 90 | | |
Abstract
Endometrial cancer ranks as the second most common gynecological cancer and the sixth prevailed cancer overall among women. Compared to other cancers, endometrial cancer is fairly common, it represented 3.6% of all new cancer cases in the USA in 2017.It was estimated that there will be 61380 new cases of endometrial cancer and an estimated 10920 people will die of this disease. In developing countries endometrial cancer represented 2.5% of all cancer cases. This made it the third cause of death from women’s gynecological cancers, behind ovarian and cervical cancer. The current study showed that the majority of Egyptian endometrial malignant cases occurred in the sixth & seventh decades of life and most of the endometrial cancer cases that undergoing surgical resection were at grade II.
The present work was conducted on a total of 50 cases of endometrial tissue cases divided as; control group consisted of 10 normal endometrial tissue samples, benign group consisted of 20 benign endometrial hyperplasia samples and malignant group consisted of 20 endometrioid adenocarcinoma of different grades. Gross examination of surgically excised tissues was done by describing and measuring the tumor size dimensions. Samples from the tumor and adjacent normal tissues were processed based on standard after a 24-hour fixation in 10% n-formaldehyde and embedded into paraffin blocks followed by routine staining with hematoxylin-eosin to establish histopathological diagnosis in Pathology Department, Faculty of Medicine.
Detecting immunohistochemical staining of ER & PR , (WT1) and (Fn14) as diagnostic biomarkers in human endometrial carcinoma versus benign endometrial hyperplasia and normal endometrial tissues, as well as their correlation with different pathological and histological parameters were accurately estimated in Histochemistry and Cell Biology Department, Medical Research Institute.
The clinicopathological parameters of this study represented by, the age ranges of control, benign and malignant groups were 30-50 ,31- >60 and 41- >60 years with mean ± SD of 40.0±7.45, 51.35 ± 15.64 and 60.65 ± 12.34 years respectively(Table 8). The second parameter is the tumor size in which 35% of the malignant cases were reported entoto, 25% were 4cm, 20% were 3cm and 20% were 6cm (Table 9).
Fifty percent of the benign cases were diagnosed as simple hyperplasia, while 40% of the studied cases were represented as simple endometrial hyperplasia with atypia , 5% of the cases were complex hyperplasia without atypia and 5% cases were hyperplastic end polyp. The majority of the malignant cases (70%) were diagnosed as endometrioid adenocarcinoma, while 15% were represented with papillary serous adenocarcinoma, 10% with endometrium clear cell carcinoma and 5% as serous adenocarcinomas (Table10).
The greater number of the malignant cases (60%) was diagnosed as grade II, while the smaller number (20%) of cases diagnosed as grade I as well as Grade III were represented by 20% of the malignant cases (Table11). Besides clinicopathological factors, molecular biological prognostic factors contribute to better tumor characterization and thus more precisely determine its clinical behavior.
Summary and Conclusions
64
Glycogen and mucin increased activities are of the common features of endometrial cancer as well. The histochemical techniques of the periodic acid Shiff and alcian blue staining were applied to detect glycogen and mucin contents. Quantitative assessement of the area percentage was done using Image J Software (Tables12 &13).
It is a well-established fact that estrogen female sex hormone imbalance is the primary hormone that can create a variety of disorders. Increased production level of estrogen was found to be responsible for the development of endometrial cancer after it enters the cell and activate estrogen receptors on the nuclear membrane. Our present results reported that, 60% of control endometrium cases were ER negative (-ve), while 40% of the benign cases were ER moderate (2+) and 30% of the malignant cases were ER strong (3+)(Table 14).
As regards to malignancy grade , the immunohistochemical staining results showed 25% moderate positive (2+) ER of grade I cases, while 41% ER strong positive (3+) of grade II and 50% ER moderate positive (2+) of grade III. The results illustrated no significant differences between the three grades (Table 15). As to the staining results of entoto cases 28% were ER moderate positive (2+), while 50% of 3cm were ER weak positive (1+),40% of 4cm were ER weak positive (1+) and 50% of 6cm were ER weak positive (1+)(Table 16).
Immunohistochemical staining of PR showed that 60% of control cases were PR weak positive, while 55% of benign cases were PR strong positive (3+) and 40% of malignant cases were PR strong positive (3+)(Table 17). As stated, 50% of grade I cases were PR moderate positive (2+), while 50% of grade II were PR strong positive (3+) and 50% of grade III were PR strong positive (3+) (Table 18). In addition ,57% of entoto cases were PR strong positive (3+), while 50% of 3cm were PR moderate positive (2+),40% of 4cm were PR strong positive (3+) and 50% of 6cm were PR strong positive (3+)(Table 19).
To expand the knowledge on the biological role of WT1 protein we focused on its detection in endometrial tissues since its expression contributes to the carcinogenesis in endometrial cancer provided additional prognostic information. Comparing the staining patterns of WT1 demonstrated in the studied samples,50% of control cases were WT1 weak positive (1+), while 70% of benign were WT1 weak positive (1+) and 40% of malignant cases were WT1 weak positive (1+)(Table 20) .
To compare WT1 expression, it was also evaluated by IHC positivity and malignant grade. It was shown that 50% of grade I cases were WT1 weak positive (1+), while 33% of grade II were WT1 moderate positive (2+) and 50% of grade III were WT1 weak positive (1+) (Table 21). Regarding to the immunohistochemical staining results of WT1 relating to the tumor size , the entoto cases 42.9% were WT1 strong positive (3+), while 50% of 3cm were WT1 moderate positive (2+), 40% of 4cm were WT1 strong positive (3+) and 50% of 6cm were WT1 moderate positive (2+)(Table 22) .
Fn14 was used parallel with ER &PR as valuable prognostic markers in endometrial cancer. Fn14 was expressed at low levels in normal tissues, its pathway activation found to promote cancer cells apoptosis which provide a new therapeutic target for human endometrium cancer treatment. Our results of Fn14 staining showed that 100% of control cases were Fn14 weak positive(1+), while 45% of benign were Fn14 moderate positive
Summary and Conclusions
65
(2+) and 45% of malignant cases were Fn14 weak positive (1+)(Table23). As stated by immunohistochemical results ,75% of grade I cases were Fn14 weak positive (1+), while 41.7% of grade II were Fn14 moderate positive (2+) and 50% of grade III were Fn14 strong positive (3+)(Table24). As regards the immunohistochemical analysis and tumor size ,42.9% of entoto cases were Fn14 moderate positive (2+), 50% of 3cm were Fn14 strong positive (3+), 80% of 4cm were Fn14 weak positive (1+) and 50% of 6cm were Fn14 strong positive (3+)(Table 25). The results were statistically verified using statistical software package SPSS 20 and for all the tests p ≤ 0.05 was considered statistically significant.
A goal for the future should be further classification of endometrial cancer subtypes based on their genetic alterations, especially those with prognostic significance. It is probable that future histological classifications will rely more on the molecular basis. For the eventual practical diagnostically therapeutic use of molecular biological factors, additional studies are needed.