Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma
Yıl: 2007 Cilt: 8 Sayı: 4 Sayfa Aralığı: 408 - 414 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022
Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma
Öz: Amaç: Sporadik Evre IB-IC endometrioid endometriyum kanser olgularında nükleer kromozom 10 üstünde fosfataz ve tensin homologu silinmesi (PTEN: phosphatase and tensin homolog deleted on chromosome 10) ekspresyonu ile klinikopatolojik özellikler arasındaki ilişkiyi araştırmak. Materyal ve Metot: Komplet cerrahi evreleme işlemine tabi tutulan 65 Evre IB-IC endometrioid endometriyum kanser olgusu üzerinde retrospektif olarak çalışıldı. Hasta yaşı, vücut kitle indeksi, tümor gradı, immünohistokimyasal nükleer PTEN ekspresyonu ve klinik sonuç incelendi. Medyan izlem süresi 49 ayd› (8-78 ay). Sonuçlar: İmmünohistokimyasal çalışma sonucunda olguların 20’sinde (%30.8) nükleer PTEN ekspresyonu pozitif olarak bulundu. Olguların 36’sında (%55.4) nükleer PTEN ekspresyonu azalmışken 9 olguda (%13.8) tamamen kayıptı. Boyanma durumu değerlendirildiğinde 45 olguda (%69.2) nükleer PTEN ekspresyonunun negatif olduğu bulundu. İzlem sürecinde 65 olgudan 5’inde (%7.7) klinik nüks saptandı. Nükleer PTEN ekspresyonunun pozitif bulunduğu olgulardaki 5 yıllık hastalıksız sağkalım, nükleer PTEN ekspresyonunun negatif bulunduğu hastalardaki 5 yıllık hastalıksız sağkalımdan farklılık göstermiyordu (%75.2’ye karşın %91.3, p=0.728 [log-rank test]). Nükleer PTEN ekspresyonu pozitif bulunan olguların ortalama vücut kitle indeksinin nükleer PTEN ekspresyonu negatif bulunan olguların ortalama vücut kitle indeksinden belirgin şekilde daha büyük olduğu saptandı (32.5±6.5’e karşın 28.5±5.0, p=0.009).Tartışma: Kayıp/azalmış nükleer PTEN ekspresyonu, Evre IB-IC endometrioid endometriyum kanserinde sık rastlanılan bir bulgudur. İmmünohistokimyasal nükleer PTEN ekspresyonunu etkileyen tek klinikopatolojik değişken, vücut kitle indeksidir.
Anahtar Kelime: Konular:
Evre IB-IC endometrioid endometriyum kanserinde vücut kitle indeksi immünohistokimyasal nükleer PTEN ekspresyonuyla ilişkilidir
Öz: Objective: To examine the relationship between clinicopathologic features and nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in a homogeneous group of Stage IB-IC sporadic endometrioid endometrial cancer (EEC) patients. Materials and Methods: This study was conducted on 65 consecutive EEC patients with FIGO Stage IB-IC disease who underwent initial complete surgical staging. Age, body mass index (BMI), tumor grade, immunohistochemical nuclear PTEN expression and clinical outcome were examined. The median follow-up period was 49 months (range, 8 to 78 months). Results: Immunohistochemical staining revealed positive nuclear PTEN expression in 20 cases (30.8%). Nuclear PTEN was found out to be reduced in 36 cases (55.4%), whereas it was completely lost in nine cases (13.8%). After evaluating the staining status, 45 cases (69.2%) were judged as “negative” for nuclear PTEN expression. During the follow-up period, clinical recurrence of disease was documented in five of 65 women (7.7%). The 5-year disease free survival rate for patients with positive nuclear PTEN expression was similar to that for patients with negative nuclear PTEN expression (75.2% vs. 91.3%, respectively; p=0.728 [log-rank test]). The mean body mass index (BMI) of positive nuclear PTEN expressing cases was significantly greater than that of patients with negative nuclear PTEN expression (32.5±6.5 vs. 28.5±5.0, respectively; p=0.009). Discussion: Lost/reduced nuclear PTEN expression was frequent in FIGO Stage IB/IC EEC. BMI is the only clinicopathologic variable affecting immunohistochemical nuclear PTEN expression.
Anahtar Kelime: Konular:
Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Li J, Ye"n C, Liaw D et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997;275:1943-7. 2. Li DM, Sun H. TEP1, encoded by a candidate tumor suppressor locus is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res 1997;57:2124-9. 3. Steck PA, Perhouse MA, Jasser SA et al. Identification of a candidate tumour suppressor gene, MMAC1 at chromosome 10q23,3 that is mutated in multiple advanced cancers. Nat Genet 1997;15:356-62. 4. Maehama T, Taylor GS, Dixon JE. PTEN and myotubularin: Novel phosphoinositide phosphatases. Annu Rev Biochem 2001;70:274-9. 5. Leslie NR, Downes CP. PTEN: The down side of PI3-kinase signaling. Cell Signal 2002;14:285-95. 6. Simpson L, Parsons R. PTEN: Life as a tumour suppressor. Exp Cell Res 2001;264:29-41. 7. Maehama T, Dixon JE. PTEN: A tumor suppressor that functions as a phospholipid phosphatase. Trends Cell Biol 1999;9:125-8. 8. Orchiston EA, Bennett D, Leslie NR et al. PTEN M-CBR3, a versatile and selective regulator of inositol 1,3,4,5,6-pentakiphosphate (Ins(1,3,4,5,6) P5). Evidence for Ins(1,3,4,5,6)P5 as a prolferative signal. J Biol Chem 2004;279:1116-22. 9. Iijma M, Huang YE, Luo HR et al. Novel mechanism of PTEN regulation by its phosphotidylinositol 4,5-biphosphate binding motif is critical for chemotaxis. J Biol Chem 2004;279:16606-13. 10. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57-70. 11. Leslie NR, Downes CP. PTEN function: How normal cells control it and tumour cells lose it. Biochem J 2004;382:1-11. 12. Tamura M, Gu J, Matsumato K et al. Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 1998;280:1614-7. 13. Di Cristofano A, Pandolfi PP. The multiple roles of PTEN in tumor suppression. Cell 2000;387-90. 14. Mutter GL, Lin M-C, Jeffrey T et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000;92:924-31. 15- Kinzler KW, Vogelstein B. Cancer-susceptibility genes. Gatekeepers and caretakers. Nature 1997;386:761-3. 16. Ali IU. Gatekeeper for endometrium: The PTEN tumor suppressor gene. J Natl Cancer Inst 2000;92(11):861-3. 17. Matias-Guiu X, Catasus L, Bussaglia E et al. Molecular pathology of endometrial hyperplasia and carcinoma. Hum Pathol 2001;32:569-77. 18. Sun H, Enomoto T, Fujita M et al. Mutational analysis of the PTEN gene in endometrial carcinoma and hyperplasia. Am J Clin Pathol 2001;115:32-8. 19. Bussaglia E, del Rio E, Matias-Guiu X, Prat J. PTEN mutations in endometrial carcinomas: A molecular and clinicopathologic analysis of 38 cases. Hum Pathol 2000;31:312-7. 20. Gimm O, Perren A, Weng LP et al. Differential nuclear and cytoplasmic expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid tumors. Am J Pathol 2000;156:1693-700. 21. Perren A, Komminoth P, Saremaslani P et al. Mutation and expression analyses reveal differential subcellular compartmentalization of PTEN in endocrine pancreatic tumors compared to normal islet cells. Am J Pathol 2000;157:1097-103. 22. Whiteman DC, Zhou XP, Cummings MC et al. Nuclear PTEN expression and clinicopathologic features in a population-based series of primary cutaneous melanoma. Int J Cancer 2002;99:63-7. 23. Ginn-Pease ME, Eng C. Increased nuclear PTEN is associated with G0-G1 in MCF-7 cells. Cancer Res 2003;63:282-6. 24. Chung JH, Eng C. Nuclear-cytoplasmic partioning of PTEN differentially regulates the cell cycle and apoptosis. Cancer Res 2005;65:8096-100. 25. Shen WH, Balajee AS, Wang J et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell 2007;128(1):157-70. 26. Trotman LC,Wang X, Alimonti A et al. Ubiquination regulates PTEN nuclear import and tumor suppression. Cell 2007;128(1):141-56. 27. Gil A, Andres-Pons A, Fernandes E et al. Nuclear localization of PTEN by a Ran-dependent mechanism enhances apoptosis: Involvement of an N-terminal nuclear localization domain and multiple nuclear exclusion motifs. Mol Biol Cell 2006;17:4002-13. 28. Inaba F, Kawamata H, Teramoto T et al. PTEN and p53 abnormalities are indicative and predictive factors for endometrial carcinoma. Oncol Rep 2005;13:17-24. 29. International Federation of Gynecology and Obstetrics: Annual report on the results of treatment in gynecologic cancer. Int J Gynecol Obstet 1989;28:189-90. 30. Greggi S, Genuardi M, Benedetti-Panici P et al. Analysis of 138 consecutive ovarian cancer patients: Incidence and characteristics of familial cancers. Gynecol Oncol 1990;39:300-4. 31. Risinger JI, Hayes AK, Maxwell GL et al. PTEN mutation in endometrial cancer is associated with favorable clinical and pathologic characteristics. Clin Cancer Res 1998;4:3005-10. 32. Kaaks R, Lukanova A, Kurzer MS. Obesity, endogenous hormones, and endometrial cancer risk: A synthetic review. Cancer Epidemiol Biomarkers Prev 2002;11:1531-43. 33. Key TJ, Pike M. The dose effect relationship between “unopposed” oestrogens, and endometrial mitotic rate: Its central role in explaining, predicting endometrial cancer risk. Br J Cancer 1988;57:205-12. 34. Salvesen HB, Akslen LA. Molecular pathogenesis and prognostic factors in endometrial carcinoma. APMIS 2002;110:673-89. 35. Parazzini F, LaVecchia C, Bocciolone L, Franceschi S. The epidemiology of endometrial cancer. Gynecol Oncol 1991;41:1-16. 36. Pavelka JC, Ben-Shachar J, Fowler JM et al. Morbid obesity and endometrial cancer: Surgical, clinical, and pathologic outcomes in surgically managed patients. Gynecol Oncol 2004;95:588-92. 37. Anderson B, Connor JP, Andrews JI et al. Obesity and prognosis in endometrial cancer. Am J Obstet Gynecol 1996;174:1171-9. 38. Everett E, Tamimi H, Greer B et al. The effect of body mass index on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer. Gynecol Oncol 2003;90:150-7. 39. Temkin SM, Pezzullo JC, Hellmann M et al. Is body mass index an independent risk factor of survival among patients with endometrial cancer? Am J Clin Oncol 2007;30(1):8-14. 40. Bokhman JV. Two pathogenic types of endometrial cancer. Gynecol Oncol 1983;15:10-7. 41. Guzeloglu-Kayisli O, Kayisli UA, Al-Rejjal R et al. Regulation of PTEN expression by estradiol and progesterone in human endometrium. J Clin Endocrinol Metab 2003;88:5017-26. 42. Mutter GL, Lin MC, Fitzgerald JT et al. Changes in endometrial PTEN expression throughout the human menstrual cycle. J Clin Endocrinol Metab 2000;85:2334-8. 43. Mutter GL. PTEN, a protean tumor suppressor. Am J Pathol 2001;158(6):1895-8. 44. Campbell RA, Bhat-Nakshatri P, Patel NM et al. Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor α.J Biol Chem 2001;276:9817-24. 45. Kato S, Kitamoto T, Masuhiro Y, Yanagisawa J. Molecular mechanism of a crosstalk between estrogen and growth-factor signaling pathways. Oncology 1998;55:5-10. 46. Kimura F, Watanabe J, Hata H et al. PTEN immunohistochemical expression is suppressed in G1 endometriod adenocarcinoma of the uterine corpus. J Cancer Res Clin Oncol 2004;130:161-8. 47. Tashiro H, Blazes MS, Wu R et al. Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res 1997;57:3935-40. 48. Maxwell GL, Risinger JI, Alvarez AA et al. Favorable survival associated with microsatellite instability in endometrioid endometrial cancers. Obstet Gynecol 2001;97:417-22. 49. McCourt CK, Mutch DG, Gibb RK et al. Body mass index: Relationship to clinical, pathologic and features of microsatellite instability in endometrial cancer. Gynecol Oncol 2007;104:535-9. 50. Barakat RR, Lev G, Hummer AJ et al. Twelve-year experience in the management of endometrial cancer: A change in surgical and postoperative radiation approaches. Gynecol Oncol 2006;doi:10.1016/j.gyno.2006. 11.007 51. Maneschi M, Maneschi F, Geraci P et al. Surgical pathological staging of endometrial carcinoma and results of treatment. Eur J Gynaecol Oncol 1992;13 (Suppl 1):30-5. 52. Salvesen HB, Stefansson I, Kalvenes MB et al. Loss of PTEN expression is associated with metastatic disease in patients with endometrial carcinoma. Cancer 2002;94:2185-91.
| APA | MEYDANLI M, KARADAĞ N, KÖSE F, TULUNAY G, ÖZFUTTU A (2007). Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma. , 408 - 414. |
| Chicago | MEYDANLI Mutlu,KARADAĞ Neşe,KÖSE Faruk,TULUNAY Gökhan,ÖZFUTTU Ahmet Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma. (2007): 408 - 414. |
| MLA | MEYDANLI Mutlu,KARADAĞ Neşe,KÖSE Faruk,TULUNAY Gökhan,ÖZFUTTU Ahmet Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma. , 2007, ss.408 - 414. |
| AMA | MEYDANLI M,KARADAĞ N,KÖSE F,TULUNAY G,ÖZFUTTU A Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma. . 2007; 408 - 414. |
| Vancouver | MEYDANLI M,KARADAĞ N,KÖSE F,TULUNAY G,ÖZFUTTU A Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma. . 2007; 408 - 414. |
| IEEE | MEYDANLI M,KARADAĞ N,KÖSE F,TULUNAY G,ÖZFUTTU A "Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma." , ss.408 - 414, 2007. |
| ISNAD | MEYDANLI, Mutlu vd. "Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma". (2007), 408-414. |
| APA | MEYDANLI M, KARADAĞ N, KÖSE F, TULUNAY G, ÖZFUTTU A (2007). Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma. Journal of the Turkish-German Gynecological Association, 8(4), 408 - 414. |
| Chicago | MEYDANLI Mutlu,KARADAĞ Neşe,KÖSE Faruk,TULUNAY Gökhan,ÖZFUTTU Ahmet Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma. Journal of the Turkish-German Gynecological Association 8, no.4 (2007): 408 - 414. |
| MLA | MEYDANLI Mutlu,KARADAĞ Neşe,KÖSE Faruk,TULUNAY Gökhan,ÖZFUTTU Ahmet Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma. Journal of the Turkish-German Gynecological Association, vol.8, no.4, 2007, ss.408 - 414. |
| AMA | MEYDANLI M,KARADAĞ N,KÖSE F,TULUNAY G,ÖZFUTTU A Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma. Journal of the Turkish-German Gynecological Association. 2007; 8(4): 408 - 414. |
| Vancouver | MEYDANLI M,KARADAĞ N,KÖSE F,TULUNAY G,ÖZFUTTU A Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma. Journal of the Turkish-German Gynecological Association. 2007; 8(4): 408 - 414. |
| IEEE | MEYDANLI M,KARADAĞ N,KÖSE F,TULUNAY G,ÖZFUTTU A "Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma." Journal of the Turkish-German Gynecological Association, 8, ss.408 - 414, 2007. |
| ISNAD | MEYDANLI, Mutlu vd. "Body mass index is associated with immunohistochemical nuclear phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in stage IB-IC endometrioid endometrial carcinoma". Journal of the Turkish-German Gynecological Association 8/4 (2007), 408-414. |
