محمد حلبيةمحمد حلبية عضو ماسي
[align=right]عنوان البحث[/align]
•تفسير السلوك البيولوجي السليم للشوكوم المتقرن بالمقارنة مع السرطانة حرشفية الخلايا في الجلد باستخدام طاقم الأضداد المناعية تجاه :
•EGFR ، P21ras, P53 , Cyclin D1

•The interpretation of benign biologic behavior for Keratoacanthoma versus Cutaneous Squamous Cell Carcinoma, using a panel of antibodies against : EGFR , P21 ras, P53 , Cyclin D1
[align=right]هدف البحث[/align]
•دراسة تعبير عدة مورثات ورمية تمثل مختلف مناحي التسرطن في الخلية :
• EGFR كمستقبلة غشائية
• P21 ras كناقلة للإشارة في الهيولى
•P53 كمورثة كابحة للورم ومنظمة للإنتساخ الDNA
•Cyclin D1 كبروتين منظم لإدارة الخلية ويعمل في تنظيم نشاط المورثة الكابحة للورم Rb

•البحث عن النقطة الفاصلة بين الشوكوم المتقرن باعتباره كارسينوما مجهضة
( متراجعة ) والسرطانة الحرشفية في الجلد من خلال دراسة تعبير هذه المورثات السابقة الذكر.
The aim of this work was to unmask the molecular relation of this tumor to SCC by studying the expression of a set of oncoproteins : EGFR (Epithelial Growth Factor Receptors,P21 ras , P53 ,Cyclin D1.

•The keratoacanthoma (KA) is a relatively common tumor which most often occurs on the sun – exposed areas of light skinned individuals of middle age and older.
•This tumor is regressing spontaneously ,so the recognition of the true nature of this tumor is of considerable practical and biological important
•It may be named as an aborted squamous cells carcinoma.?
•Its etiology is unlcear , although ultraviolet light , viruses, oncogenic chemicals, and epidermal growth factor have been considered.
•EGFR : is membrane growth factor receptor encoded by the Cerb 1 gene
•P21 ras: is a signal transducing ( cytoplasmic ) oncoprotein with GTP ase activity. Ras mutative abolishes GTP ase activity and results in constitutive stimulation of the way.
•P 53 Nuclear protein playing an important protective role in the response to DNA damage induced by ionizing radiation chemical carcinogens and viruses, by three man mechanisms :
1- G1 arrest by induction of WAF 21 factor.
2- DNA damage repair by induction of GADD 45.
3- Induction of apoptosis in a situation of DNA damage repair failure.
* Cyclin D 1: CDK Complex regulates the RB protein ( PRB) . Mutational gene causes hyperphosphory lat of RB protein .with consultative stimulation of the pathway
•دراسة حوالي 50 حالة لمرضى أجري لهم استئصال شقي أو كامل بهدف التشخيص النسجي للآفات التالية:
• الشوكوم المتقرن والسرطانة الحرشفية مع دراسة عينات من الجلد الطبيعي كشاهد
•دراسة الحالات الحدية والمحيرة بين الشوكوم المتقرن والسرطانة الحرشفية
•تلوين مناعي نسجي لبروتينات المورثات
•EGFR,P53, P21 ras, Cyclin D1
•دراسة مورفوميترية لتعبير هذه البروتينات الورمية
•دراسة كمية ونوعية لتعبير هذه البروتينات الورمية في الشوكوم المتقرن والسرطانة الحرشفية الخلايا.
•دراسة إحصائية مقارنة لتعبير هذه البروتينات الورمية في الورمين السابقين





•The expression of P21 ras was more evident in KA versus SCC (14/24 -58 % in KA versus 5/26- 19% in SCC ( P < 0.05)




•EGFR was negative in both all cases of KA and SCC
•But focally expressed in the neighboring reactive epithelium



Cyclin D1 showed more evident ( focal expression ) in SCC ( 10/26 -38% in SCC versus 4/24 – 16 % in KA )




•- Our results refer to the decisive role of P53 mutation in the development of SCC and Its invaluable role in setting down a convincing diagnosis of SCC.
•- P21 ras was more definitive in KA
•- EGFR : is expressed more in reactive and benign epidermal growths , and has no role in both KA and SCC.
•– P53 mutation is critical and decisive in the development of cutaneous malignancy.
•- Cutaneous malignancy may be ascribed more to mutation in nuclear oncoproteins

•1- Petersen S, Iggo R,Corradin G.
Cytotoxic T epitopes in P53 protein: effect of mutation and polymorphism on peptide binding to purified and refold HLA molecules.
( Scand J Immunol.2001 ;53: 357-64)
•2- Lu S, Tiesko J, Hietnen S, Syrjanen K.
Expression of cell-cycle protein P53(WAF-1),PCNA and Ki67 in Benign , pre - malignant and malignant skin lesions with implicated HPV involvement.
( Acta Derm Venereolo. 1999 Jul,790(4) :268-73.
•3- Vielba R,Bilbao J,Ispizua I,
P53 and Cyclin D1 as prognostic factors in SCC of the larynx.
(Laryngoscop.2003 jan:113(1):167-72

•4- L Mortier MD, PM Danze PhD, P Plouvier,
Comparison of Keratoacanthoma and SCC, the point of view of micro satellites.
( 7th International Symposium on Predictive Oncology. February 7-10 , 2004 )
•5- A.P.B. Black & G.S.OGG.
The role of P53 in the immunobiology of cutaneous SCC.
( Clinical & experimental Immunology Volume 132 Issue 3 page 379 –June 2003-60
•6- Hernandez J, Lee PP, Davis MM, Sherman LA.
•The use of HLA 2,1 /p53 peptide teramers to visualize the impact of self tolerance on the TCR repertoire.
•J Immunol. 2000;164:596-602
•7- Ferries E,Connan F, Pages F et al.
•Identification of p53 peptides recognized by CD 8 (+) T lymphocytes from patients with bladder cancer.
•Hum Immunol 2001;62:791-8
•8- Moch C, Moysan A, Lubin R et al.
•Divergence between the high rate P 53 mutations in skin carcinomas and the low prevalence of anti – P 53 antibodies.
•Br. J cancer 2001;85:1883 – 6.

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