p53 ve p73 EKSPRESYON DÜZEYİ KOLOREKTAL KANSER İÇİN TANISAL BİR BELİRTEÇ MİDİR?

Öz

Kanser gelişiminde rolü olduğu gösterilen bazı moleküllerdeki genetik değişimler hastalık tanı, tedavi ve seyrinin takibinde belirleyici olarak kullanılabilmektedir. Kolorektal kanserlerde ise, tümör supressör genlerde meydana gelen birçok genetik değişim tam açıklanmamış olup araştırılması devam etmektedir. Bu nedenle sunulan bu çalışmada; kolorektal kanserli hastaların, normal ve tümör dokuları arasındaki p53 ve p73 geni ekspresyon düzeyi değişimlerinin belirlenmesi ve bu değişimlerin, hastalara ait klinik ve patolojik özellikler ile ilişkisinin saptanması amaçlandı. Çalışmaya, 19 kolorektal kanser hastasından alınan, 19’u normal ve 19’u tümör dokusu olmak üzere, toplam 38 kolorektal doku örneği dahil edildi. p53 ve p73 ekspresyon düzeyi analizleri, RT-PCR ve yarı ölçümsel dansitometrik analizler kullanılarak gerçekleştirildi. Normal ve tümör dokuları arasında p53 ve p73 ekspresyon düzeyleri açısından fark bulunamadı. Yüksek p53 ekspresyonu saptanan hastaların ise ileri patolojik evrelerde oldukları ancak bu hastalara ait tümörlerin metastatik olmadıkları gösterildi. Sonuç olarak, elde ettiğimiz veriler doğrultusunda, p53 ve p73 ekspresyon düzeyi değişimlerinin saptanmasının, kolorektal kanser tümör biyolojisinin anlaşılmasına katkıda bulunacağı ve hasta prognozlarının belirlenmesinde birer prediktif marker olarak kullanılabilineceği düşünülmüştür

Anahtar Kelimeler

• Kolorektal kanser, p53, p73, ekspresyon düzeyi, RT-PCR

Are p53 and p73 Expression Levels a Diagnostic Marker in Colorectal Cancer?

Öz

The genetic changes in some molecules that underlie malign transformation of cells can be used as markers to diagnose, monitor or characterize various forms of cancer. Though in colorectal cancer, many of the genetic changes have continued to be studied in tumor supressor genes, this study aims to clarify the expression pattern of p53, and p73 genes between normal and tumor colorectal tissues and corralate with clinicopathological features. A total of 38 tissue samples (19 normal and 19 tumor tissue)from 19 patients with colorectal cancer were included in this study. The expression of p53 and p73 have been investigated by using the RT-PCR and semi-quantitative densitometric approaches. Between the normal and tumor tissues was found no difference of p53 and p73 expression levels. In patients with high levels expression levels of p53, pathological stage was found significantly more advanced than that of the cases expressing low levels of p53, and these tumors were not metastatic. Our study suggests that the detection of expressional changes of p53, and p73 might contribute to further understanding of the tumor biology of colorectal cancer and could serve as predictive markers for patient prognosis

Anahtar Kelimeler

• Colorectal cancer, p53, p73, expression level, RT-PCR

Kaynakça

1. Chang F, Syrjanen S, Kurvinen K, et al. The p53 Tumor Suppressor Gene as a Comman Cellular Target in Human Carcinogenesis. Am J Gastroenterol 1993, 88(2): 174-86.
2. Bénard J, Douch-Rasy S, Ahomadegbe JC. TP53 Family Members and Human Cancers. Hum Mutat 2003, 21: 182-91.
3. Kaghad M, Bonnet H, Yang A, et al. Monoallelically Expressed Gene Related to p53 at 1p36.3, a Region Frequently Deleted in Neuroblastoma and Other Human Cancers. Cell 1997; 90(4): 809-19.
4. Davis PK, Dowdy SF. Molecules in Focus p73. Int J Biochem Cell Biol 2001, 33: 935-9.
5. Ichimiya S, Nakagawara A, Sakuma Y, et al. p73: Structure and Function. Pathol Int 2000, 50: 589-93.
6. Marin MC, Kaelin WG Jr. p63 and p73: Old Members of a New Family. Bichim Biophys Acta 2000, 1470: M93-100.
7. Soengas MS, Lowe SW. p53 and p73: Seeing Double? Nat Genet 2000, 26: 391-2.
8. Chen CL, Ip SM, Cheng D, et al. p73 Gene Expression in Ovarian Cancer Tissues and Cell Lines. Clin Cancer Res 2000; 6: 3910-5.

9. Peters UR, Tschan MP, Kreuzer KA, et al. Distinct Expression Patterns of the p53- Homologue p73 in Malignant and Normal Hematopoiesis Assessed by a Novel Real-Time Reverse Transcriptase-Polymerase Chain Reaction Assay and Protein Analysis. Cancer Res 1999, 59: 4233-6
10. Galizia G, Ferraraccio F, Lieto E, et al. Prognostic Value of p27, p53, and Vascular Endothelial Growth Gactor in Dukes A and B Colon Cancer Patients Undergoing Potentially Curativ Surgery. Dis Colon Rectum 2004, 47:1904-14.
11. Iacopetta B. TP53 Mutation in Colorectal Cancer. Hum Mutat 2003, 21:271-6.
12. Xiangming C, Hokita S, Natsugoe S, et al. p21 Expression is a Prognostic Factor in Patients with p53-Negative Gastric Cancer. Cancer Lett 2000; 148: 181-8.
13. Liu XP, KawauchiS, Oga A, et al. Combined Examination of p27Kip1, p21Waf1/Cip1 and p53 Expression Allows Precise Estimation of Prognosis in Patients with Gastric Carcinoma. Histopathol 2001, 39: 603-10.
14. Okuyama T, Meahara Y, et al. Combined Evaluation of Expression of p53 and p21 Proteins as Prognostic Factors for Patients with Gastric Carcinoma. Oncology 2002, 63: 353-61.
15. Noda H, Maehara Y, Irie K, et al. Growth Pattern and Expression of Cell Cycle Regulator Proteins p53 and p21WAF1/Cıp1 in Early Gastric Carcinoma. Cancer 2001, 92(7): 1828-35.
16. Kawano S, Miller CW, Gombart AF, et al. Loss of p73 Gene Expression in Leukemias/ Lymphomas Due to Hypermethylation. Blood 1999, 94(3): 1113-20.
17. Chi SG, Chang SG, Lee SJ, et al. Elevated and Biallelic Expression of p73 is Associated with Progression of Human Bladder Cancer. Cancer Res 1999, 59: 2791-3.
18. Zaika AI, Kovalev S, Marchenko ND, et al. Overexpression of the Wild Type p73 Gene in Breast Cancer Tissues and Cell Lines. Cancer Res 1999, 59: 3257-63.
19. Tokuchi Y, Hashimoto T, Kobayashi Y, et al. The Expression of p73 is Increased in Lung Cancer, Independent of p53 Gene Alteration. Br J Cancer 1999, 80(10): 1623-9.
20. Zwahlen D, Tschan MP, Grob TJ, et al. Differential Expression of p73 Splice Variants and Protein in Benign and Malignant Ovarian Tumours. Int J Cancer 2000, 88: 66-70.
21. Kang MJ, Park BJ, Byun DS, et al. Loss of Imprinting and Elevated Expression of Wild- Type p73 in Human Gastric Adenocarcinoma. Clin Cancer Res 2000, 6: 1767-71.