الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
ndometrial cancer is the most common gynaecological malignancy in the developed world. The majority of cases can be divided into two broad categories based on clinico-pathological and molecular characteristics; Type I oestrogen-dependent with endometrioid morphology and Type II non-oestrogen-dependent with serous papillary or clear cell morphology. The transition from normal endometrium to carcinoma is thought to involve a stepwise accumulation of alterations in cellular regulatory pathways leading to dysfunctional cell growth.
The Her-2/neu gene is a member of a family of genes encoding transmembrane receptors for growth factors, including the epidermal growth factor receptor (EGFR), HER2, HER3, and HER4. The intracellular domain of HER2 has tyrosine kinase activity that regulates important aspects of the physiology, growth, and differentiation of cells. Extracellular domains of the Her-2/neu protein interact with HER family members, allowing Her-2/neu to serve as a coreceptor and to facilitate signal transduction as part of a heterodimer complex that forms after ligand binding.
Overexpression of HER-2/neu (HER) is associated with unfavorable prognosis of endometrial cancer. It occur with high grade endometrial carcinoma. Overexpression in case of serous carcinoma occur from 25% up to 40% of cases.
The purpose of this study was to: to evaluate Her-2/neu gene expression in cases of proliferative, secretory, hyperplastic and neoplastic endometrium and to correlate Her-2/neu gene expression with tumor type, grade and depth of invasion and or lymph node involvment.
The present study included 75 specimens of hysterectomy and endometrial biopsies. They included normal, hyperplastic and endometrial carcinomas, received in the Pathology Laboratory of Sohag University Hospital from the Department of Obstetrics and Gynaecology through the period from March 2016 to May 2018.
The H & E stained sections of the 75 cases were evaluated. Five cases were normal endometrium (3 of them proliferative and 2 secretory cases), 20 cases were hyperplastic (12 simple and 8 complex). There were 37/50 of cases (74%) were endometrioid carcinoma, 10/50 (20%) of them were serous carcinoma, One case 1/50 (2%) were clear cell carcinoma and 2/50 of cases (4%) were Undifferentiated carcinoma.
The Endometrioid carcinoma cases were graded in accordance with the WHO (2014) into:
- Grade I: < 5% non-squamous, non-morular growth pattern: 25/50 of cases.
- Grade II: 6-50% non-squamous, non-morular growth pattern: 11/50 of cases.
- Grade III: > 50% non-squamous, non-morular growth pattern: 1/50 of cases.
The age range of the 50 patients was 40-80 years the mean age was 59.4 years, and median age was 60 years. The tumor size were ≤3 cm in 9/50 (18%) of cases and > 3cm in 30/50 (60%) of cases were. Regarding type of biopsy, 38/50 (78%) of cases were hysterectomy and 11/50 (22%) cases were D&C. Most patients 28/50 (56%) of cases presented with post-menopausal bleeding, 7/50 (14%) presented by peri-menopausal bleeding, 11/50 (22%) cases presented by uterine mass and 4/50 (8%) cases presented with uterine polyp.
Regional lymph node metastasis was positive in 11/50 (22%) cases. One case (1/50) (2%) of endometrioid carcinoma showed foci of squamous differentiation.
Sections from the 75 cases were immunostained with Her-2/neu to detect their expressions and they revealed that: Her-2/neu was positive in 38/50 (76%) of all cases of endometrial carcinoma (31 of them were endometrioid, 6 were serous and 1 was poorly differentiated) , 14/20 (70%) of all cases of endometrial hyperplasia, and 2/5 (40%) of all cases of normal endometrium (the 2 positive normal cases were disordered proliferative endometrium).
The positive cases were classified as following: In endometrial carcinoma: 14/50 (28%) showed strong expression (10 endometrioid and 4 serous), 24/50 (48%) showed moderate expression (21 endometrioid, 2 serous and 1 case undifferentiated carcinoma). In endometrial hyperplasia: 1/20 (5%) of cases showed strong expression, 13/20 (65%) of cases showed moderate expression. Normal endometrium cases showed that: 1/5 (20%) of cases showed strong expression and 1/ 5 (20%) showed moderate expression.
Our study showed that Immunohistochemical staining of endometrial carcinoma with Her-2/neu gave significant results according to tumour grade p=0.013, tumour stage (p= 0.05) and invasion to the myometrium (P=0.012).
However, statistical evaluation of Her-2/neu expression according to age, tumor size and lymph node status showed no significant correlation with Her-2/neu expression.
Conclusion
In case of Her-2/neu expression in endometrial carcinoma, There was a decrease in expression of Her-2/neu with increasing the tumor grade with a statistically significant difference P value <0.013, but overexpression in serous carcinoma and other high grade tumors occur in 25-40% of cases.
Considering tumor stage, we found significant decrease in Her-2/neu expression with increasing stage of the tumor (P-value 0.05)
Recommendations
1. Studying the expression of Her-2/neu on a large scale of cases of endometrial cancer.
2. Follow up of patients to emphasize the correlation between Her-2/neu expression and the prognosis of disease, patient survival, disease outcome and effect of therapy against target agent.