Identification of proliferation markers in endometrial carcinoma
Authors:
V. Šišovský; Ľ. Danihel; P. Babál; M. Palkovič; J. Jakubovský; B. Bučeková; M. Budaj; A. Molnárová
Published in:
Prakt Gyn 2008; 12(4): 236-244
Práce je převzata z časopisu Praktická gynekológi a, 2007; 14(3): 112–120 na základě spolupráce redakcí našich časopisů a dohody o výměně odborných prací.
Overview
Endometrium is a specialised tissue characteristic by intravital changes of its morphological appe arance as well as of the expression of different proteins. A total of 60 formalin‑fixed and paraffin‑embedded biopsy tissue samples with proliferative (PE, 10) and secretory (SE, 10) endometrium, endometrio id G1 (ECG1, 10) and G3 (ECG3, 10), serous (SC, 10) and cle ar cell (CCC, 10) endometrial carcinoma (ECa) were evalu ated immunohistochemically (IHC) for the expression of PCNA, Ki- 67 and p53 proteins in the nuclei of endometrial epithelial cells. The expression of PCNA and Ki- 67 was high in PE, with considerable decre ase in SE. In CaE, the ex pression of PCNA and Ki- 67 was high and did not significantly differ from the ex pression in PE and in various histological subsets and grades of ECa. The highest expression of PCNA and Ki- 67 was in the subset of aggressive ECa. The expression of p53 was related only to aggressive (mainly SC and ECG3, less CCC) types of ECa and to the worse clinical behavior of the oncological illnesses. In conclusion, the pro‑teins p53, Ki- 67 and PCNA are important prognostic markers of ECa. Evalu ation of these proteins by IHC is an relatively inexpensive and simple method with implica tions for clinical practice. In ECa there is an incre ased expression of p53. Ki- 67 and PCNA are excellent markers of malignant transformation of endometrial cells espe cially in postmenopa usal period that do not produce under normal conditions (Tab. 1, Fig. 8) [73].
Key words:
endometrial carcinoma – proliferation markers – PCNA – Ki- 67 – p53 – im munohistochemistry – prognostic markers.
Sources
1. American Cancer Society: 2000 cancer statistics. CA Cancer J Clin 2000; 50(1): 1– 64.
2. Anderson MC et al. Endometrial carcinoma. In: Robboy SJ, Anderson MC, Russell P (eds). Pathology of the Female Reproductive Tract. London: Churchill Livingstone 2002: 331– 359.
3. Aronica SM, Katzenellenbogen BS. Progesterone receptor regulation in uterine cells: stimulation by estrogen, cyclic adenosine 3’,5’- mono- phosphate and insulin‑like growth factor I and suppression by antiestrogens and protein kinase. Endocrinology 1991; 128: 2045- 2052.
4. Azumi N, Czernobilsky B. Immunohistochemistry (1251– 1276). In: Kurman RJ (ed). Bla ustein’s Pathology of the Female Genital Tract. 5. ed. New York: Springer-Verlag 2002: 1391.
5. Bandera CA, Boyd J. The molecular genetics of endometrial carcinoma. In: Aldaz CM et al (eds). Etiology of bre ast and Gynecological Cancers. Progres in Clinical and Biological Rese arch. New York: Willey- Liss 1977: 185– 203.
6. Bokhman N. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983; 15: 10– 17.
7. Breitenecker G, Lax S. Tumoren des Corpus uteri einschliesslich der Plazenta (97– 102). In: Histologische Tumor Klassifikation. Wien, New York: Springer- Verlag 1994: 432.
8. Budaj M, Bučeková B, (Šišovský V, Danihel Ľ, školitelia). Identifikácia markerov proliferačnej aktivity v karcinóme endometria. 46. fakultná konferencia ŠVOČ. Zborník prác, Bratislava: LF UK a Slovak Academic Press, 2007a: 22– 25. (Práca ocenená diplomom Dekana LF UK v Bratislave za prácu I. poradia, 1. miesto).
9. Budaj M, Bučeková B, (Šišovský V, Danihel Ľ, Repiská V, mentors). Identification of Proliferation Markers in Correlation with p53 Gene Mutation in Endometrial Carcinoma. 18th Europe an Students Conference. Abstracts. Berlin: October 7th– 11th, 2007b.
10. DakoCytomation: DakoCytomation 2004/ 05 Catalog. Denmark: Glostrup 2004: 359.
11. Danihel Ľ, Babál P, Porubský J, Zaviačič M, Breitenecker G, Janek Ľ. Imunohistochemické markery v diagnostike nádorov maternice. Bratisl lek Listy 1995; 96(7): 353– 360.
12. Danihel Ľ, Breitenecker G. Histologická diagnostika nenádorových a nádorových zmien endometria v peri- a postmenopa uze (14– 41). In: P. Šuška, K. Holomáň (eds). Endometrium v peri- a postmenopa uze. Bratislava: Slovak Academic Press 1997: 186.
13. Danihel Ľ, Gomolčák P, Korbeľ M, Pružinec J, Vojtaššák J, Janík P, Babál P. Expression of proliferation and apoptotic markers in human placenta during pregnancy. Acta Histochem 2002; 104(4): 335– 338.
14. Danihel Ľ, Horváth R, Breitenecker G, Hatzibugias I. Súčasná klasifikácia a charakteristika nádorov endometria. Slov gynek por 2003;10(Suppl 1): 14– 17.
15. Danihel Ľ, Porubský J. Prínos monoklonálnych protilátok v bioptickej diagnostike nádorov. Bratisl lek Listy 1991; 92(9): 460– 466.
16. Danihel Ľ, Šišovský V, Palkovič M, Hatzibugias D, Hatzibugias I. Karcinóm endometria – histopatologická klasifikácia a charakteristika. Gynekol prax 2005; 3(1): 9– 12.
17. Deligdisch L, Cohen CJ. Histologic correlates and virulence implications of endometrial carcinoma associated with adenomatous hyperplasia. Cancer 1985; 56(6): 1452– 1455.
18. Elhafey AS, Papadimitriou JC, El- Hakim MS, El- Said AI, Ghannam BB, Silverberg SG. Computerized image analysis of p53 and proliferating cell nucle ar antigen expression in benign, hyperplastic, and malignant endometrium. Arch Pathol Lab Med 2001; 125(7): 872– 879.
19. Geisler JP, Wiemann MC, Zhou Z, Miller GA, Geisler HE. p53 as a prognostic indicator in endometrial cancer. Gynecol Oncol 1996; 61: 245– 248.
20. Gomolčák P, Danihel Ľ, Šišovský V. E- cadherin, a‑inhibin a calponin – biologicky aktívne látky v štruktúrach trofoblastu. Lojdov histochemický deň. Slovenská histochemická spoločnosť, Ústav patologickej anatómie LF UK, Výskumný ústav srdca SAV. Abstrakty. Bratislava: 2005:. 8.
21. Gusberg SB. Detection and prevention of uterine cancer. Cancer 1988; 62: 1784– 1786.
22. Hamel NW, Sebo TJ, Wilson TO, Keeney GL, Roche PC, Suman VJ, Hu TC, Podratz KC. Prognostic value of p53 and proliferating cell nucle ar antigen expression in endometrial carcinoma. Gynecol Oncol 1996; 62(2): 192– 198.
23. Hareyama H. Proliferative activity of normal endometrial cells, endometrial hyperplasia cells and endometrial cancer cells using the monoclonal antibody to PCNA. Hokkaido Igaku Zasshi 1994; 69(6): 1427– 1431.
24. Chen YP, Shen M, Chen C. Study on expression of PCNA and estrogen, progesterone receptors in endometrial carcinoma. Hunan Yi Ke Da Xue Xue Bao 2001; 26(2): 123– 125.
25. Ioffe OB, Papadimitriou JC, Drachenberg CB. Correlation of proliferation indices, apoptosis, and related oncogene expression (bcl- 2 and c- erbB- 2) and p53 in proliferative, hyperplastic, and malignant endometrium. Hum Pathol 1998; 29(10): 1150– 1159.
26. Ito K, Sasano H, Watanabe K, Ozawa N, Sato S, Yajima A. Immunohistochemical study of PCNA (proliferating cell nucle ar antigen) in normal and abnormal endometrium. Int J Gynecol Cancer 1993; 3(2): 122– 127.
27. Ito K, Sasano H, Yabuki N, Matsunaga G, Sato S, Kikuchi A, Yajima A, Nagura H. Immunohistochemical study of Ki- 67 and DNA topo isomerase II in human endometrium. Mod Pathol 1997; 10(4): 289– 294.
28. Jakubovský J. Nekorektnosť vo vedeckom bádaní (424– 442). In: . Hulín I (ed). Základy vedeckej práce. Bratislava: Slovak Academic Press 2003: 553.
29. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafo or A, Fe uer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin 2005; 55(1): 10– 30. In: CA Cancer J Clin 2005; 55(4): 259.
30. Kerns BJ, Jordan PA, Mo ore MB, Humphrey PA, Berchuck A, Kohler MF, Bast RC Jr, Iglehart JD, Marks JR. p53 overexpression in formalin‑fixed, paraffin‑embedded tissue detected by immunohistochemistry. J Histochem Cytochem 1992; 40(7): 1047– 1051.
31. Khalifa MA, Mannel RS, Haraway SD, Walker J, Min KW. Expression of EGFR, HER- 2/ ne u, P53, and PCNA in endometrio id, serous papillary, and cle ar cell endometrial adenocarcinomas. Gynecol Oncol 1994; 53: 84– 92.
32. Lax SF, Pizer ES, Ronnett BM, Kurman RJ. Cle ar cell carcinoma of the endometrium is characterized by a distinctive profile of p53, Ki- 67, estrogen, and progesterone receptor expression. Hum Pathol 1998; 29: 551– 558.
33. Lax SF. Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular‑based classification. Virchows Arch 2004; 444(3): 213– 223.
34. Liu FS. Molecular carcinogenesis of endometrial cancer. Taiwan J Obstet Gynecol 2007; 46(1): 6– 32.
35. Lodish H, Berk A, Matsudaira P et al. Molecular cell biology. 5th Edn. New York: W. H. Freeman and company 2004.
36. Molnárová A, Kováčová E, Majtán J, Fedeleš J, Bieliková E, Cvachová S, Vojtaššák J, Repiská V. Chlamydia and mycoplasma infections during pregnancy and their relationships to orofacial cleft. Biologia 2006; 61(6): 719– 723.
37. Mutter GL, Ferenczy A. Anatomy and histology of the uterine corpus (383–419). In: Kurman RJ (ed). Bla ustein’s Pathology of the Female Genital Tract. 5 .ed. New York: Springer- Verlag 2002: 1391.
38. Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JP, Lees JA et al. Altered PTEN expression as a diagnostic marker for the e arliest endometrial precancers. J Natl Cancer Inst 2000; 92: 924– 930.
39. Okamoto A, Sameshima Y, Yamada Y, Teshima S, Terashima Y, Terada M, Yokota J. Allelic loss on chromosome 17p and p53 mutations in human endometrial carcinoma of the uterus. Cancer Res 1991; 51(20): 5632– 5635.
40. Parazzini F, La Vecchia C, Negri E, Moroni S, Chatenoud L. Smoking and risk of endometrial cancer: results from an Italian case- control study. Gynecol Oncol 1995; 56: 195– 199.
41. Pleško I et al. Incidencia zhubných nádorov v Slovenskej republike v roku 1990. Bratislava: Aktu al klin Onkol 1994: 115.
42. Pleško I et al. Incidencia zhubných nádorov v Slovenskej republike 2000. Bratislava: Národný onkologický ústav, Ústav experimentálnej onkológie SAV, Národný onkologický register Slovenskej republiky 2003: 207.
43. Poradovský K. Nádory ženských pohlavných orgánov (141– 161). In: A. Ponťuch (ed). Gynekológia a pôrodníctvo. Martin: Osveta 1984: 404.
44. Redecha M, Korbeľ M, Sasko A. Histologické nálezy endometria pri krvácaní v klimaktériu a séniu. Prakt Gynek 1996; 3: 61– 64.
45. Redecha M, Nižňanská Z, Korbeľ M. Klinická charakteristika karcinómu endometria. Gynekol prax 2005; 3(4): 13– 16.
46. Redecha M, Nižňanská Z, Korbeľ M. Výskyt zhubných nádorov tela maternice na Slovensku v rokoch 1990– 2000. Gynekol prax 2004; 2(4): 194– 199.
47. Repiská V, Zummerová A, Miklóši M, Breza J, Böhmer D, Vojtaššák J. Využitie metódy RT‑PCR pri detekcii cirkulujúcich mikrometastáz. Rozhledy v chirurgii 2003; 82(2): 95– 102.
48. Robboy SJ, Anderson MC, Russell P. Pathology of the Female reproductive tract. London – Edinburg – New York – Philadelphia: Churchill Livingstone 2002: 929.
49. Robboy SJ, Duggan MA, Kurman RJ. Gynecologic Pathology (942– 989). In: Rubin E, Farber JL (eds). Pathology. Philadelphia: J. B. Lippincott Company 1988: 1576.
50. Ronnett BM, Kurman RJ. Precursor Lesion of Endometrial carcinoma (467– 500). In: Kurman RJ (ed). Bla ustein’s Pathology of the Female Genital Tract. 5 .ed. New York: Springer- Verlag 2002: 1391.
51. Ronnett BM, Zaino RJ, Ellenson LH, Kurman RJ. Endometrial Carcinoma (501– 559). In: Kurman RJ (ed). Bla ustein’s Pathology of the Female Genital Tract. 5 .ed. New York: Springer Verlag 2002: 1391.
52. Sakuragi N, Hareyama H, Todo Y, Yamada H, Yamamoto R, Fujino T, Sagawa T, Fujimoto S. Prognostic significance of serous and Clar cell adenocarcinoma in surgically staged endometrial carcinoma. Acta Obstet Gynecol Scand 2000; 79(4): 311– 316.
53. Salvesen HB, Iversen OE, Akslen LA. Identification of high- risk patients by assessment of nucle ar Ki- 67 expression in a prospective study of endometrial carcinomas. Clin Cancer Res 1998; 4: 2779– 2785.
54. Scully RE, Bonfiglio TA, Kurman RJ, Silverberg SG, Wilkinson EJ. Histologic Typing of Female Genital Tract Tumours (International histological classification of tumours). 2 .ed. New York: Springer- Verlag 1994: 189.
55. Silverberg SG, Kurman RJ, Nogales F, Mutter GL, Kubik- Huch RA, Tavassoli FA. Epithelial Tumors and Related Lesions (221– 232). In: F. A. Tavassoli, P. Devilee (Eds) WHO classification of Tumours, Pathology and Genetics, Tumours of the Bre ast and Female Genital Organs. Tumours of the Uterine Corpus. Lyon: IARC Press 2003: 432.
56. Silverberg SG, Kurman RJ. Tumors of the Uterine Corpus and Gestational Trophoblastic Ddise ase. Atlas of Tumor Pathology. Washington, D. C: 1992. Armed Forces Institute of Pathology (AFIP), 3, Fasc. 3: 290(232).
57. Sivridis E, Fox H, Huckley CH. Endometrial carcinoma – two or three entities? Int J Gynecol Cancer 1988: 183– 188.
58. So ong R, Knowles S, Williams KE, Hammond JG, Wysocki SJ, Iacopetta BJ. Overexpression of p53 protein is an independent prognostic indicator in human endometrial carcinoma. Br J Cancer 1996; 74: 562– 567.
59. Šišovský V. Imunohistochemická analýza endometria za fyziologických a patologických stavov. Dizertačná práca. Bratislava: Univerzita Komenského 2005: 144.
60. Šišovský V, Danihel Ľ, Babál P, Jakubovský J, Porubský J, Palkovič M, Korbeľ M, Hatzibougias D, Hatzibougias I, Bučeková B, Kopáni M. Expresia kyseliny sialovej v endometriu za fyziologických stavov, v hyperplázii endometria a v karcinóme endometria. XIV. vedecká konferencia slovenských a českých patológov s medzinárodnou účasťou. Mojmírovce: Zborník vedeckých prác 2006c.
61. Šišovský V, Danihel Ľ, Babál P, Zaviačič M, Porubský J, Palkovič M, Redecha M, Hatzibougias D, Hatzibougias I, Bučeková B, Biró C. Imunohistochemická analýza expresie vybraných proteínov v endometriu za fyziologických stavov, v hyperplázii endometria a v karcinóme endometria. XIV. vedecká konferencia slovenských a českých patológov s medzinárodnou účasťou. Mojmírovce: Zborník vedeckých prác 2006b.
62. Šišovský V, Danihel Ľ, Jakubovský J, Bučeková B, Babál P. The identification of sialic acid in normal endometrium and in endometrial carcinoma (85). In: Tribulová N, Okruhlicová Ľ (eds). Potential therape utic targets in cardiovascular and other dise ases. Bratislava: VEDA 2006e: 88.
63. Šišovský V, Danihel Ľ, Štvrtina S, Porubský J, Zaviačič M, Redecha M, Korbeľ M, Palkovič M, Bučeková B, Gomolčák P. Angiogenéza v endometriu za fyziologických stavov, v hyperplázii endometria a v karcinóme endometria. XIV. vedecká konferencia slovenských a českých patológov s medzinárodnou účasťou. Mojmírovce: Zborník vedeckých prác 2006a.
64. Šišovský V, Palkovič M, Babál P, Jakubovský J, Porubský J, Bučeková B, Danihel Ľ. The expression of the selected proteins in endometrial carcinoma (79– 84). In: Tribulová N, Okruhlicová Ľ eEds) Potential therape utic targets in cardiovascular and other dise ases. Bratislava: VEDA 2006d: 88.
65. Šišovský V, Palkovič M, Zeljenková D, Kobzová D, Czirfus A, Balážová K, Michalka P, Jakubovská V, Wsólová L, Jakubovský J. Pôsobenie derivátov organofosfátov na reprodukčné orgány samíc potkanov Wistar. 12. kongres Slovenskej a Českej spoločnosti patológov s medzinárodnou účasťou. Bratislava: Zborník vedeckých prác 2004: 48.
66. Šuška P, Holomáň K. Endometrium v peri- a postmenopa uze. Bratislava: Slovak Academic Press 1997: 186.
67. Šuška P. Nádory maternice (182– 200). In: Šuška P (ed). Vybrané kapitoly z gynekológie. Bratislava: Univerzita Komenského 2003. 254.
68. Tabibzadeh S. Immunore activity of human endometrium: correlation with endometrial dating. Fertil Steril 1990; 54: 624– 631.
69. Tashiro H, Isacson C, Levine R, Kurman RJ, Cho KR, Hedrick L. p53 gene mutations are common in uterine serous carcinoma and occur e arly in their pathogenesis. Am J Pathol 1997; 150: 177– 185.
70. Weismanová E, Weismann P, Vizváryová M, Lehotská V, Križanová O, Repiská V, Ka ušitz J. New appro ach to human high- risk papillomavirus (HR- HPV) genotyping. Neoplasma 2002; 49(4): 217– 224.
71. Wheeler DT, Bell KA, Kurman RJ, Sherman ME. Minimal uterine serous carcinoma: Diagnosis and clicopathologic correlation. Am J Surg Pathol 2000; 24: 797– 806.
72. Yu CC, Wilkinson N, Brito MJ, Buckley CH, Fox H, Levison DA. Patterns of immunohistochemical staining for proliferating cell nucle ar antigen and p53 in benign and neoplastic human endometrium. Histopathology 1993; 23(4): 367– 371.
73. Zavadil M, Motlík K. Pohlavní ústrojí ženy (1233– 1336). In: Bednář B (ed) Patologie III. Praha: Avicenum 1984: 1856.
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