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العنوان
Comparative Study of Immunohistochemical Expression of Erythroblastosis E26 Rearrangement Gene (ERG) and Membrane-associated Guanylate kinase (MAGI-2) in Prostatic Carcinoma /
المؤلف
Bahbah, Alaa Mohamed Nasser Hamed.
هيئة الاعداد
باحث / آلاء محمد ناصر حامد بحبح
مشرف / هيام عبد السميع عياد
مشرف / محمد ابراهيم شعبان
مشرف / مروة محمد داود
الموضوع
Prostate - Cancer. Prostatic neoplasms.
تاريخ النشر
2019.
عدد الصفحات
192 P. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الطب
تاريخ الإجازة
26/9/2019
مكان الإجازة
جامعة المنوفية - كلية الطب - الباثولوجي
الفهرس
Only 14 pages are availabe for public view

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Abstract

Nodular prostatic hyperplasia (NPH) is a benign disease that characterized by excessive growth of the prostatic tissue. NPH occur after the age of 40. Half of males at the age of 50 years are affected. In Egypt, NPH represents 41.3% of all prostatic lesions.
Prostate cancer is the most common cancer in men in the United States, after skin cancer. It is the second cause of death from cancer in men. Almost all prostate cancers are prostatic adenocarcinomas. In Egypt, prostate cancer represents 48.01% of all prostatic lesions and 61.63% of all male genital tract malignancy.
This study aimed to evaluate the diagnostic and prognostic value of immunohistochemical expression of ERG and MAGI-2 in prostatic carcinoma in comparison to each other.
This study was carried on 56 cases of prostatic adenocarcinoma (PCa) specimens and 29 cases of nodular prostatic hyperplasia (NPH) from Egyptian patients, retrieved from the Pathology Department, Faculty of Medicine, Menoufia University as well as private labs, during the period from March 2018 to October 2018.
The age of the cases with nodular prostatic hyperplasia ranged from 49 to 78 years (mean 65.86 y). Among the 29 cases of nodular prostatic hyperplasia, total serum PSA level ranged from 3ng/ml to 26ng/ml (mean 9.67).
 Summary
156
The age of prostatic adenocarcinoma cases ranged from 51 to 86 years old (mean 65.79). Among the 56 cases of prostatic adenocarcinoma, the total serum PSA level ranged from 38 ng/ml to 240 ng/ml (mean 87.6)
On studying the histopathological parameters in prostatic adenocarcinoma cases, all the studied cases were of acinar subtype. All cases of prostatic adenocarcinoma were graded according to the modified Gleason grading system. Most of adenocarcinoma cases were of Gleason’s score 6 and 7 (75%). Perineural invasion was seen in 5 cases and vascular invasion was absent in all cases.
ETS-related gene (ERG) is a member of ETS oncogene family and is located on human chromosome 21, band q22. Genes in the ETS family have role in regulating embryonic development, cell cycle control, cell proliferation, differentiation apoptosis, migration and angiogenesis. Some studies; in prostate cancer; referred to increased ERG protein expression which thought to be reflective of ERG gene rearrangement.
In the present study all NPH cases, NPH adjacent to carcinoma and HGPIN adjacent to carcinoma showed negative expression of ERG in prostatic acini.
Regarding prostatic adenocarcinoma, positive ERG expression was seen in 29 cases /56 cases (51.8%) and 27 cases (48.2%) showed negative expression. The most predominant intensity was strong intensity in 16 cases (55.2%).
A statistically highly significant difference was detected between NPH and prostatic adenocarcinoma regarding ERG
 Summary
157
expression, total percent of positivity; intensity of predominant and H score (p value < 0.001 for all).
A statistically significant inverse relationship could be detected between ERG positive cases and ERG negative cases regarding Gleason grading score (p value <0.05) and Gleason grading group (p value = 0.01).
The diagnostic power of ERG in differentiating NPH from prostatic carcinoma cases revealed 53.6 % sensitivity and 100% specificity.
Regarding possible prognostic significance of ERG in PCa, a significant relationship was detected between Ki-67 and H-score of ERG, it was an inverse relation where high Ki-67 was related to low H score. On the other hand, a significant relationship was found between Ki-67 and expression of ERG where positive ERG expression was associated with low Ki-67. Thus ERG positive cases had good prognosis than ERG negative cases evidenced by low Gleason score and low Ki-67 index in ERG positive cases.
Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI-2): Is a scaffolding protein that links cell adhesion molecules, receptors and signaling molecules to the cytoskeleton and maintains the architecture of cell junctions. MAGI-2 gene rearrangements have been recently described in prostate cancer.
In NPH, positive MAGI-2 expression was only detected in 5 cases /29 cases (17.2%). In NPH adjacent to carcinoma, positive MAGI-2 expression was seen in 6 cases /10 cases (60%).
 Summary
158
All cases of HGPIN adjacent to carcinoma were positive for MAGI-2 (3 cases). While in PCa positive MAGI-2 expression was seen in (51 /56) cases (91.1%). Intensity of cytoplasmic staining of MAGI-2 in prostatic carcinoma in current study was significantly higher in HGPIN and cancer compared to NPH (p<0.001). The later observation as well as distribution of the positive cases in the studied groups is interesting because it suggests that MAGI-2 may play role in prostate carcinogenesis.
A statistically highly significant difference was detected between NPH and prostatic adenocarcinoma regarding MAGI-2 expression, total percent of positivity, intensity of predominant and H score (p value <0.001 for all).
A statistically significant difference was detected between NPH and NPH adjacent to carcinoma regarding total percent of positivity only (p value 0.02).
The diagnostic power of MAGI-2 in differentiating NPH from prostatic carcinoma at H score cut of point 85 by ROC curve revealed 91.1% sensitivity and 86.2% specificity.
In conclusion, as ERG revealed high specificity but low sensitivity and MAGI-2 revealed higher sensitivity than ERG but less specific, so from the view of this study the best result for diagnosis of prostatic carcinoma can be obtained by combination of both markers by test in parallel. This combination will increase the sensitivity to 95% and 100% specificity. Moreover, this study couldn‘t prove any significant relation between both ERG and MAGI-2 and couldn‘t support the prognostic role of MAGI-2 neither good prognostic nor poor prognostic.