Yıl: 2015 Cilt: 45 Sayı: 1 Sayfa Aralığı: 118 - 128 Metin Dili: İngilizce İndeks Tarihi: 29-07-2022

Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer

Öz:
Background/aim: To assess the prognostic value of Ki-67, p27, and p53 immunoreactivity in human gastric cancer. Materials and methods: A total of 84 patients with gastric cancer participated in our study. We categorized tumors as intestinal and diffuse types, with reference to Lauren s classification. Ki-67, p27, and p53 immunoreactivity were correlated with patient s age, tumor type, grade, lymph node status, extent of invasion, tumor-node-metastasis (TNM) stage, and survival. Results: Decreased expression of p27 (<20% positivity of cells) and increased p53 staining (>50% positivity of cells) were determined in 41 (48.8%) and 29 (36.9%) tumor specimens, respectively, and were connected with both the TNM stage (P = 0.007 and P = 0.039, respectively), and the extent of tumor invasion (P = 0.025 and P = 0.004, respectively). Kaplan Meier methods showed a remarkable effect of reduced p27 expression on survival time (P = 0.003). In contrast, we observed no notable relationship between survival time and p53 or Ki-67 immunoreactivity (P = 0.372 and P = 0.401, respectively). Conclusion: A decrease in p27 expression and overexpression of p53 or Ki-67 may cause advancing and metastatic illness in patients with gastric carcinoma. In addition, immunopathological identification of p27 may be helpful to define patients with gastric cancer who are at an increased risk of death.
Anahtar Kelime:

Konular: Cerrahi
Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Mattioli E, Vogiatzi P, Sun A, Abbadessa G, Angeloni G, D’Ugo D, Trani D, Gaughan JP, Vecchio FM, Cevenini G et al. Immunohistochemical analysis of pRb2/p130, VEGF, EZH2, p53, p16INK4A, p27KIP1, p21WAF1, Ki-67 expression patterns in gastric cancer. J Cell Physiol 2007; 210: 183–191.
  • 2. Bilici M, Tekin SB, Kandaz M, Çayır K, Ertekin MV, Özmen HK. The evaluation of the results of adjuvant chemoradiotherapy in patients with gastric cancer: results from a single center in eastern Anatolia. Turk J Med Sci 2012; 42: 329–336.
  • 3. André AR, Ferreira MVP, Mota RMS, Ferrasi AC, Pardini MI, Rabenhorst SH. Gastric adenocarcinoma and Helicobacter pylori: correlation with p53 mutation and p27 immunoexpression. Cancer Epidemiol 2010; 34: 618–625.
  • 4. Altınkaynak K, Bilici M, Bakan N, Akçay F. Circulating levels of IGF-I and IGFBP-3 in gastric cancer. Turk J Med Sci 2012; 42: 1458–1462.
  • 5. Nagini S. Carcinoma of the stomach: a review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol 2012; 4: 156–169.
  • 6. Mills SA, Contos MJ, Goel R. The stomach. In: Silverberg SG, DeLellis RA, Frable WJ, LiVolsi VA, Wick MR, editors. Silverberg’s Principles and Practice of Surgical Pathology and Cytopathology. 4th ed. Philadelphia, PA, USA: Churchill Livingstone; 2006. pp. 1321–1372.
  • 7. Rosai J. Stomach. In: Rosai J, editor. Rosai and Ackerman’s Surgical Pathology. 9th ed. London, UK: Elsevier; 2004. pp. 649–711.
  • 8. Shibata A, Longacre TA, Puligandla B, Parsonnet J, Habel LA. Histological classification of gastric adenocarcinoma for epidemiological research: concordance between pathologists. Cancer Epidemiol Biomarkers Prev 2001; 10: 75–78.
  • 9. Craanen ME, Blok P, Dekker W, Offerhaus GJ, Tytgat GN. Chronology of p53 protein accumulation in gastric carcinogenesis. Gut 1995; 36: 848–885.
  • 10. Correa P, Piazuelo MB, Camargo MC. Etiopathogenesis of gastric cancer. Scand J Surg 2006; 95: 218–224.
  • 11. Bashir SA, Pandith AA, Yousuf A, Parveen N, Siddiqi MA, Muddassar S, Andrabi KI, Abdin MZ. Lack of p16 gene mutations in gastric cancers in Kashmir. Asian Pac J Cancer Prev 2010; 11: 339–342.
  • 12. Lloyd RV, Erickson LA, Jin L, Kulig E, Qian X, Cheville JC, Scheithauer BW. p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers. Am J Pathol 1999; 154: 313–323.
  • 13. Sandhu C, Slingerland J. Deregulation of the cell cycle in cancer. Cancer Detect Prev 2000; 24: 107–118.
  • 14. Abbas NF, El-Sharkawy SL, Fadel MT, Abd El-Monem ElShaer M, Abd El-Megid B, El-Said Abd El-Aal W. Combined expression of P27 and P53 in human gastric carcinoma. Report and Opinion 2010; 2: 27–34.
  • 15. Wen S, So Y, Singh K, Slingerland JM, Resnick MB, Zhang S, Ruiz V, Moss SF. Promotion of cytoplasmic mislocalization of p27 by Helicobacter pylori in gastric cancer. Oncogene 2012; 31: 1771–1780.
  • 16. Gamboa-Dominguez A, Seidl S, Reyes-Gutierrez E, Hermannstädter C, Quintanilla-Martinez L, Busch R, Höfler H, Fend F, Luber B. Prognostic significance of p21WAF1/CIP1, p27Kip1, p53 and E-cadherin expression in gastric cancer. J Clin Pathol 2007; 60: 756–761.
  • 17. Sgambato A, Migaldi M, Leocata P, Ventura L, Criscuolo M, Di Giacomo C, Capelli G, Cittadini A, De Gaetani C. Loss of p27Kip1 expression is a strong independent prognostic factor of reduced survival in N0 gastric carcinomas. Cancer 2000; 89: 2247–2257.
  • 18. Müller W, Borchard F. Prognostic influence of p53 expression in gastric cancer. J Pathol 1996; 178: 255–258.
  • 19. Van den Berg FM, Baas IO, Polak MM, Offerhaus GJ. Detection of p53 overexpression in routinely paraffin-embedded tissue of human carcinomas using a novel target unmasking fluid. Am J Pathol 1993;142: 381–385.
  • 20. de Manzoni G, Verlato G, Tomezzoli A, Guglielmi A, Pelosi G, Ricci F, Di Leo A, Cordiano C. Study on ki-67 immunoreactivity as a prognostic indicator in patients with advanced gastric cancer. Jpn J Clin Oncol 1998; 28: 534–537.
  • 21. Cattoretti G, Becker MH, Key G, Duchrow M, Schlüter C, Galle J, Gerdes J. Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin fixed paraffin sections. J Pathol 1992; 168: 357–363.
  • 22. Key G, Becker MHG, Duchrow M, Duchrow M, Schlüter C, Flad HD, Gerdes J. New Ki-67 equivalent murine monoclonal antibodies (Mib 1-3) prepared against recombinant parts of the Ki-67 antigen. Ann Cell Pathol 1992; 4: 181–183.
  • 23. Kakeji Y, Korenaga D, Tsujitani S, Haraguchi M, Maehara Y, Sugimachi K. Predictive value of ki-67 and argyrophilic nucleolar organizer region staining for lymph node metastasis in gastric cancer. Cancer Res 1991; 51: 3503–3506.
  • 24. Lazăr D, Tăban S, Sporea I, Dema A, Cornianu M, Lazăr E, Goldiş A, Vernic C. Ki-67 expression in gastric cancer. Results from a prospective study with long-term follow-up. Rom J Morphol Embryol 2010; 51: 655–661.
  • 25. Van der Woude CJ, Kleibeuker JH, Tiebosch AT, Homan M, Beuving A, Jansen PL, Moshage H. Diffuse and intestinal type gastric carcinomas differ in their expression of apoptosis related proteins. J Clin Pathol 2003; 56: 699–702.
  • 26. Kikuyama S, Kubota T, Shimizu K, Miyakita M. Ki-67 antigen expression in relation to clinicopathological variables and prognosis in gastric cancer. Oncol Rep 1998; 5: 867–870.
  • 27. Washington K. 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol 2010; 17: 3077–3079.
  • 28. Vieth M, Kushima R, Mukaisho K, Sakai R, Kasami T, Hattori T. Immunohistochemical analysis of pyloric gland adenomas using a series of Mucin 2, Mucin 5AC, Mucin 6, CD10, Ki67 and p53. Virchows Arch 2010; 457: 529–536.
  • 29. Boring CC, Squires TS, Tong T. Cancer statistics 1993. CA Cancer J Clin 1993; 43: 7–26.
  • 30. Gilliland R, Williamson KE, Wilson RE, Anderson NH, Hamilton PW. Colorectal cell kinetics. Br J Surg 1996; 83: 739– 749.
  • 31. Tubiana M, Pejovic MH, Koscielny S, Chavaudra N, Malaise E. Growth rate, kinetics of tumor cell proliferation and long term outcome in human breast cancer. Int J Cancer 1989; 44: 17–22.
  • 32. Ford HL, Sclafani RA, DeGregori J. Cell cycle regulatory cascades. In: Stein GS, Pardee AB, editors. Cell Cycle and Growth Control: Biomolecular Regulation and Cancer. Hoboken, NJ, USA: Wiley-Liss; 2004. pp. 95–128.
  • 33. Tonini T, Hillson C, Claudio PP. Interview with the retinoblastoma family members: do they help each other? J Cell Physiol 2002; 192: 138–150.
  • 34. Esposito V, Baldi A, De Luca A, Groger AM, Loda M, Giordano GG, Caputi M, Baldi F, Pagano M, Giordano A. Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer. Cancer Res 1997; 57: 3381–3385.
  • 35. Al-Moundhri MS, Nirmala V, Al-Hadabi I, Al-Mawaly K, Burney I, Al-Nabhani M, Thomas V, Ganguly SS, Grant C. The prognostic significance of p53, p27kip1, p21waf1, HER- 2/neu, and Ki67 proteins expression in gastric cancer: a clinicopathological and immunohistochemical study of 121 Arab patients. J Surg Oncol 2005; 91: 243–252.
  • 36. Wiksten JP, Lundin J, Nordling S, Kokkola A, von Boguslawski K, Haglund C. The prognostic value of p27 in gastric cancer. Oncology 2002; 63: 180–184.
  • 37. Nitti D, Belluco C, Mammano E, Marchet A, Ambrosi A, Mencarelli R, Segato P, Lise M. Low level of p27 (kip1) protein expression in gastric adenocarcinoma is associated with disease progression and poor outcome. J Surg Oncol 2002; 81: 167–176.
  • 38. Mori M, Mimori K, Shiraishi T, Tanaka S, Ueo H, Sugimachi K, Akiyoshi T. P27 expression and gastric carcinoma. Nature Med 1997; 3: 593.
  • 39. Yasui W, Kudo Y, Semba S, Yokozaki H, Tahara E. Reduced expression of cyclin-dependent kinase inhibitor p27kip is associated with advanced stage and invasiveness of gastric carcinoma. Jpn Cancer Res 1997; 88: 625–529.
  • 40. Kim DH, Lee HI, Nam ES, Shin HS, Sohn JH, Park CH, Yoon DS, Song SY, Park YE. Reduced expression of the cell-cycle inhibitor p27kip1 is associated with progression an lymph node metastasis of gastric carcinoma. Histopathology 2000; 36: 245– 251.
  • 41. Liu XP, Kawauchi S, Oga A, Suehiro Y, Tsushimi K, Tsushimi M, Sasaki K. Combined expression of p27kip1, p27Waf1/Cip1 and p53 expression allows precise estimation of prognosis in patients with gastric carcinoma. Histopathology 2001; 39: 603–610.
  • 42. Müller W, Schneiders A, Meier S, Hommel G, Gabbert HE. Immunohistochemical study on the prognostic value of MIB-l in gastric carcinoma. Br J Cancer 1996; 74: 759–765.
  • 43. Yonemura Y, Kimura H, Fushida S, Tugawa K, Nakai Y, Kaji M, Fonseca L, Yamaguchi A, Miyazaki I. Analysis of proliferative activity using anti-proliferating cell nuclear antigen antibody in gastric cancer tissue specimens obtained by endoscopic biopsy. Cancer 1993; 71: 2448–2453.
  • 44. Jain S, Filipe MI, Hall PA, Waseem N, Lane DP, Levison DA. Prognostic value of proliferating cell nuclear antigen in gastric carcinoma. J Clin Pathol 1991; 44: 655–659.
  • 45. Lee KH, Lee HE, Cho SJ, Cho YJ, Lee HS, Kim JH, Nam SY, Chang MS, Kim WH, Lee BL. Immunohistochemical analysis of cell cycle-related molecules in gastric carcinoma: prognostic significance, correlation with clinicopathological parameters, proliferation and apoptosis. Pathobiology 2008; 75: 364–372.
  • 46. Zheng Y, Wang L, Zhang JP, Yang JY, Zhao ZM, Zhang XY. Expression of p53, c-erbB-2 and Ki67 in intestinal metaplasia and gastric carcinoma. World J Gastroenterol 2010; 16: 339– 344.
  • 47. Lee WJ, Shun CT, Hong RL, Wu MS, Chang KJ, Chen KM. Overexpression of p53 predicts shorter survival in diffuse type gastric cancer. Br J Surg 1998; 85: 1138–1142.
  • 48. Kakeji Y, Korenaga D, Tsujitani S, Baba H, Anai H, Maehara Y, Sugimachi K. Gastric cancer with p53 overexpression has high potential for metastasising to lymph nodes. Br J Cancer 1993; 67: 589–593.
APA ÇALIK M, DEMİRCİ E, ALTUN E, Calik I, GÜNDOĞDU Ö, Gürsan N, GÜNDOĞDU B, Albayrak M (2015). Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer. , 118 - 128.
Chicago ÇALIK Muhammet,DEMİRCİ ELİF,ALTUN EREN,Calik Ilknur,GÜNDOĞDU Özge Beyza,Gürsan Nesrin,GÜNDOĞDU BETÜL,Albayrak Mevlut Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer. (2015): 118 - 128.
MLA ÇALIK Muhammet,DEMİRCİ ELİF,ALTUN EREN,Calik Ilknur,GÜNDOĞDU Özge Beyza,Gürsan Nesrin,GÜNDOĞDU BETÜL,Albayrak Mevlut Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer. , 2015, ss.118 - 128.
AMA ÇALIK M,DEMİRCİ E,ALTUN E,Calik I,GÜNDOĞDU Ö,Gürsan N,GÜNDOĞDU B,Albayrak M Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer. . 2015; 118 - 128.
Vancouver ÇALIK M,DEMİRCİ E,ALTUN E,Calik I,GÜNDOĞDU Ö,Gürsan N,GÜNDOĞDU B,Albayrak M Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer. . 2015; 118 - 128.
IEEE ÇALIK M,DEMİRCİ E,ALTUN E,Calik I,GÜNDOĞDU Ö,Gürsan N,GÜNDOĞDU B,Albayrak M "Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer." , ss.118 - 128, 2015.
ISNAD ÇALIK, Muhammet vd. "Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer". (2015), 118-128.
APA ÇALIK M, DEMİRCİ E, ALTUN E, Calik I, GÜNDOĞDU Ö, Gürsan N, GÜNDOĞDU B, Albayrak M (2015). Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer. Turkish Journal of Medical Sciences, 45(1), 118 - 128.
Chicago ÇALIK Muhammet,DEMİRCİ ELİF,ALTUN EREN,Calik Ilknur,GÜNDOĞDU Özge Beyza,Gürsan Nesrin,GÜNDOĞDU BETÜL,Albayrak Mevlut Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer. Turkish Journal of Medical Sciences 45, no.1 (2015): 118 - 128.
MLA ÇALIK Muhammet,DEMİRCİ ELİF,ALTUN EREN,Calik Ilknur,GÜNDOĞDU Özge Beyza,Gürsan Nesrin,GÜNDOĞDU BETÜL,Albayrak Mevlut Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer. Turkish Journal of Medical Sciences, vol.45, no.1, 2015, ss.118 - 128.
AMA ÇALIK M,DEMİRCİ E,ALTUN E,Calik I,GÜNDOĞDU Ö,Gürsan N,GÜNDOĞDU B,Albayrak M Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer. Turkish Journal of Medical Sciences. 2015; 45(1): 118 - 128.
Vancouver ÇALIK M,DEMİRCİ E,ALTUN E,Calik I,GÜNDOĞDU Ö,Gürsan N,GÜNDOĞDU B,Albayrak M Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer. Turkish Journal of Medical Sciences. 2015; 45(1): 118 - 128.
IEEE ÇALIK M,DEMİRCİ E,ALTUN E,Calik I,GÜNDOĞDU Ö,Gürsan N,GÜNDOĞDU B,Albayrak M "Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer." Turkish Journal of Medical Sciences, 45, ss.118 - 128, 2015.
ISNAD ÇALIK, Muhammet vd. "Clinicopathological importance of Ki-67, p27, and p53 expression in gastric cancer". Turkish Journal of Medical Sciences 45/1 (2015), 118-128.