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Pankreatik duktal adenokarsinomlar ve ampüller bölge adenokarsinomlarında HSF-1 ve P53 ekspresyonlarının prognostik faktörlerle ilişkisi

Yıl 2017, Cilt: 8 Sayı: 4, 168 - 174, 01.06.2017
https://doi.org/10.18663/tjcl.284388

Öz

Amaç: Periampüller bölge
adenokarsinomları; pankreas ve ampüller bölge tümörlerini içine alan, medikal
ve cerrahi tedaviye dirençli ve hızlı metastatik progresyon gösteren
tümörlerdir. Isı şok faktörü-1, ısı şok genlerini aktif hale getirir ve malign
transformasyon ve kanser hücrelerinde çoğalmayı kolaylaştırır. P53 ise
pankreatik kanserlerin %50'sinden fazlasında mutasyona uğrayan tümör
baskılayıcı bir gendir.
  Bu çalışmada
HSF-1 ve P53 ekspresyonlarının tümör boyutu, lenf nodu metastazı, tümör evresi,
tümör diferansiasyonu ve prognoz ile ilişkisi analiz edilmiştir.

Gereç ve Yöntemler: İstanbul Eğitim ve Araştırma Hastanesi'nde uygulanan 69
pankreatikoduodenektomi materyali; HSF-1/P53 ekpresyonu
,
yaş, cinsiyet,
tümör lokalizasyonu, tümör
boyutu
, tümör evresi, tümörün diferansiasyonu, lenf
nodu metastazı varlığı ve prognoz açısından yeniden araştırıldı.

Bulgular: Çalışmamızda, %10’un üzerinde
boyanma görülen olgularda, büyük tümör boyutu, ileri evre tümör varlığı, yüksek
dereceli tümör varlığı, pozitif lenf düğümü ve kötü prognoz daha fazla oranda
izlenmiştir.







Sonuçlar: Çalışmamız HSF-1 ve P53 ekspresyonlarının, özellikle
yüksek dereceli
periampüller bölge
adenokarsinomlarının
gelişiminde rol
oynadığını düşündürmektedir. Ayrıca bu iki marker, az differansiye
adenokarsinom tanısında diğer parametreler ile birlikte tercih edilebilir. 









 

Kaynakça

  • 1. World health organization classification of tumours the digestive system. 4th edition. Ed: Bosman T, Carneiro F, Hruban RH, Theise ND. IARC Press Lyon, 2010.
  • 2. Saif MW. Pancreatic cancer: İs this bleak landscape finally changing? Highlights from the 43rd ASCO Annual Meeting. Chicago, IL, USA 2007; 8: 365-73.
  • 3. Raimondi S, Lowenfels AB, Morselli AM, Maisonneuve P, Pezzilli R. Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. Best Pract Res Clin Gastroenterol 2010; 24: 349-58.
  • 4. Löhr M, Klöppel G, Maisonneuve P, Lowenfels AB, Lüttges J. Frequency of K-ras mutations in pancreatic intraductal neoplasias associated with pancreatic ductal adenocarcinoma and chronic pancreatitis: A meta analysis. Neoplasia 2005; 7; 17-23.
  • 5. Trimbath JD, Griffin C, Romans K, Giardiello FM. Attenuated Familial adenomatous polyposis as ampullary. Gut 2003; 52: 903-4.
  • 6. Balanchandran P, Sikora SS, Kapoor S, et al. Long-term survival and recurrence patterns in ampullary cancer. Pancreas 2006; 32: 390-5.
  • 7. Hanh JS, Hu Z, Thiele DJ, Iyer VR. Genome wide analysis of the biology of stres responses through heat shock transcription factor. Mol Cell Biol 2004; 24:5 2549-56.
  • 8. Dudeja V, Chugh RK, Sangwan V, et al. Prosurvival role of Heat shock factor-1 in the pathogenesis of pancreatobiliary tumors. Am J Gastrointest Liver Physiol 2011; 300; G948-55.
  • 9. Popovici A, Popescu I, Ionescu MI, et al. The periampullary carcinoma. Clinical and therapeutic alternatives. Chirurgia (Bucur) 2000; 95: 407-24.
  • 10. Filiz G, Yerci O, Adim SB, et al. Periampullary carcinomas. Hepatogastroenterology 2007; 54: 1247-49.
  • 11. Johnson CD, Özmen MM. Pankreas kanseri. Temel Cerrahi, Sayek İ (Ed), 3. baskı, Ankara, Güneş Kitabevi 2004: 1429-36.
  • 12. Nuzzo G, Clemente G, Cadeddu F, Giovannini I. Palliation of unresectable periampullary neoplasms: Surgical versus non-surgical approach. Hepatogastroenterol 2004; 51: 1282-5.
  • 13. Banerji SS, Berg L and Morimoto R. Transcriptional and post transcriptional regulation of avian HSP-70 gene expression. J Biol Chem. 1986; 261: 15740-5.
  • 14. Nakai A, Morimoto RI. Characterization of a novel chicken Heat shock transcription factor, HSF-3, suggests a new regulatory pathway. Mol Cell Biol 1993; 13:1983-97.
  • 15. Morimoto RI. Regulation of the heat shock transcriptional response: Cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 1998; 12: 3788-96.
  • 16. Dai C, Whitesell L, Rogers AB, Lindquist S. Haet shock factor 1 is a powerful multifaceted modifier of cacinogenesis. Cell 2007; 130: 1005-18.
  • 17. Mendillo ML, Santagata S, Koeva M, et al. HSF-1 drives a transcriptional program distinct from heat shock to support highly malignant human cancer. Cell 2012; 150: 549-62.
  • 18. Calderwood SK. HSF-1, a versatile factor in tumorogenesis. Curr Mol Med 2012; 12: 1102-7.
  • 19. Ishiwata J, Kasamatsu A, Sakuma K, et al. State of Heat shock factor-1 expression as a putative diagnostic marker for oral squamous cell carcinoma. Int J Oncol 2012; 40: 47-52.
  • 20. Heimberger T, Andrulis M, Riedel S, et al. The Heat shock transcription factor 1 as a potential new therapeutic in multiple myeloma. Br J Hematology 2013; 160: 465-76.
  • 21. Min JG, Huang L, Zimojik DB, Moskophisid D, Mivechi NF. Selective suppression of lymphomas by functional loss of HSF-1 in a P53, deficient mouse model for spontaneous tumors. Oncogene 2007; 26: 5086-97.
  • 22. Logan IR, McNeill HV, Cook S, et al. Heat shock factor 1 modulates P53 in the transcriptional response to DNA damage. Nucleic Acids Res 2009; 37: 2962-73.
  • 23. Vimalachandran D. Genetics and prevention of pancreatic cancer. Cancer Control 2004; 11: 6-14.
  • 24. Bardeesy N, Depinho RA. Pancreatic cancer biology and genetics. Nat Rev Cancer 2002; 2: 897-909.
  • 25. Yeo CJ, Sohn TA, Cameron JL, et al. Periampullary adenocarcinoma: analysis of 5 year survivors. Ann Surg 1998; 227: 821-31.
  • 26. Garcea G, Dennison AR, Pattenden CJ, Neal CP, Sutton CD, Berry DB. Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature. J Pancreas 2008; 9: 99-132.
  • 27. Takai S, Satoi S, Toyokawa H, et al. Clinicopathologic evaluation after resection for ductal adenocarcinoma of the pancreas: A retrospective, single institution experience. Pancreas 2003; 26: 243-9.
  • 28. Michelassi F, Erroi F, Dawson PJ, et al. Experience with 647 consecutive tumors of the duodenum, ampulla, head of the pancreas, and distal common bile duct. Ann Surg 1989; 210: 544-56.
  • 29. Keleg S, Büchler P, Ludwig R, Büchler MW, Friess H. Invasion and metastasis in pancreatic cancer. Molecular Cancer 2003; 2: 1-7.
  • 30. Ueda M, Endo I, Nakashima M, et al. Prognostic factors after resection of pancreatic cancer. World J Surg 2009; 33: 104-10.
  • 31. Riediger H, Keck T, Wellner U, et al. F. The lymph node ratio is the strongest prognostic factor after resection of pancreatic cancer. J Gastrointest Surg 2009; 13: 1337-44.
  • 32. You DD, Lee HG, Heo JS, Choi SH, Choi DW. Prognostic factors and adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic Adenocarcinoma. J Gastrointest Surg 2009; 13: 1699-706.
  • 33. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Pancreatic section, BSG, Gut 2005; 54: v1-16.

Relationship of HSF-1 and P53 expressions to prognostic factors in pancreatic ductal adenocarcinomas and ampullary region adenocarcinomas

Yıl 2017, Cilt: 8 Sayı: 4, 168 - 174, 01.06.2017
https://doi.org/10.18663/tjcl.284388

Öz

Aim: Periampullary region
adenocarcinomas, which includes pancreatic ductal adenocarcinoma and ampullary
carcinoma is one of the malignant tumors with characterized by rapid metastatic
progression and resistant to medical and surgical treatments.
Heat shock genes are activated by heat shock factor-1 and
facilitates malignant transformation and cancer cell proliferation.
  P53 is a tumor suppressor gene which
mutated in more than 50% of pancreatic cancers
. In
this study, the relation of paramaters which include tumor size, lymph node
metastasis, tumor stage, tumor grade and prognosis with HSF-1 and P53 expession
was analysed.

Material and Methods: 69
pancreaticoduodenectomy materials which performed in the Istanbul Education and
Research Hospital were researched entirely about the
HSF-1/
P53
expression, age, gender, tumor
location, tumor size, tumor stage, tumor grade, presence of lymph node
metastasis and prognosis
.

Results: In our study, tumors which stained 
>10%, had more percentage in large tumor size, advanced stage tumors,
high grade tumors, positive lymph nodes and poor prognosis.







Conclusion:
Our study suggest that HSF-1 and P53
expression plays role at carcinogenesis of
especially high grade
periampullary region adenocarcinomas. In addition, these two markers may be preferred in
combination with other parameters, at the diagnosis of poor differentiated
adenocarcinomas.













                                      

Kaynakça

  • 1. World health organization classification of tumours the digestive system. 4th edition. Ed: Bosman T, Carneiro F, Hruban RH, Theise ND. IARC Press Lyon, 2010.
  • 2. Saif MW. Pancreatic cancer: İs this bleak landscape finally changing? Highlights from the 43rd ASCO Annual Meeting. Chicago, IL, USA 2007; 8: 365-73.
  • 3. Raimondi S, Lowenfels AB, Morselli AM, Maisonneuve P, Pezzilli R. Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. Best Pract Res Clin Gastroenterol 2010; 24: 349-58.
  • 4. Löhr M, Klöppel G, Maisonneuve P, Lowenfels AB, Lüttges J. Frequency of K-ras mutations in pancreatic intraductal neoplasias associated with pancreatic ductal adenocarcinoma and chronic pancreatitis: A meta analysis. Neoplasia 2005; 7; 17-23.
  • 5. Trimbath JD, Griffin C, Romans K, Giardiello FM. Attenuated Familial adenomatous polyposis as ampullary. Gut 2003; 52: 903-4.
  • 6. Balanchandran P, Sikora SS, Kapoor S, et al. Long-term survival and recurrence patterns in ampullary cancer. Pancreas 2006; 32: 390-5.
  • 7. Hanh JS, Hu Z, Thiele DJ, Iyer VR. Genome wide analysis of the biology of stres responses through heat shock transcription factor. Mol Cell Biol 2004; 24:5 2549-56.
  • 8. Dudeja V, Chugh RK, Sangwan V, et al. Prosurvival role of Heat shock factor-1 in the pathogenesis of pancreatobiliary tumors. Am J Gastrointest Liver Physiol 2011; 300; G948-55.
  • 9. Popovici A, Popescu I, Ionescu MI, et al. The periampullary carcinoma. Clinical and therapeutic alternatives. Chirurgia (Bucur) 2000; 95: 407-24.
  • 10. Filiz G, Yerci O, Adim SB, et al. Periampullary carcinomas. Hepatogastroenterology 2007; 54: 1247-49.
  • 11. Johnson CD, Özmen MM. Pankreas kanseri. Temel Cerrahi, Sayek İ (Ed), 3. baskı, Ankara, Güneş Kitabevi 2004: 1429-36.
  • 12. Nuzzo G, Clemente G, Cadeddu F, Giovannini I. Palliation of unresectable periampullary neoplasms: Surgical versus non-surgical approach. Hepatogastroenterol 2004; 51: 1282-5.
  • 13. Banerji SS, Berg L and Morimoto R. Transcriptional and post transcriptional regulation of avian HSP-70 gene expression. J Biol Chem. 1986; 261: 15740-5.
  • 14. Nakai A, Morimoto RI. Characterization of a novel chicken Heat shock transcription factor, HSF-3, suggests a new regulatory pathway. Mol Cell Biol 1993; 13:1983-97.
  • 15. Morimoto RI. Regulation of the heat shock transcriptional response: Cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 1998; 12: 3788-96.
  • 16. Dai C, Whitesell L, Rogers AB, Lindquist S. Haet shock factor 1 is a powerful multifaceted modifier of cacinogenesis. Cell 2007; 130: 1005-18.
  • 17. Mendillo ML, Santagata S, Koeva M, et al. HSF-1 drives a transcriptional program distinct from heat shock to support highly malignant human cancer. Cell 2012; 150: 549-62.
  • 18. Calderwood SK. HSF-1, a versatile factor in tumorogenesis. Curr Mol Med 2012; 12: 1102-7.
  • 19. Ishiwata J, Kasamatsu A, Sakuma K, et al. State of Heat shock factor-1 expression as a putative diagnostic marker for oral squamous cell carcinoma. Int J Oncol 2012; 40: 47-52.
  • 20. Heimberger T, Andrulis M, Riedel S, et al. The Heat shock transcription factor 1 as a potential new therapeutic in multiple myeloma. Br J Hematology 2013; 160: 465-76.
  • 21. Min JG, Huang L, Zimojik DB, Moskophisid D, Mivechi NF. Selective suppression of lymphomas by functional loss of HSF-1 in a P53, deficient mouse model for spontaneous tumors. Oncogene 2007; 26: 5086-97.
  • 22. Logan IR, McNeill HV, Cook S, et al. Heat shock factor 1 modulates P53 in the transcriptional response to DNA damage. Nucleic Acids Res 2009; 37: 2962-73.
  • 23. Vimalachandran D. Genetics and prevention of pancreatic cancer. Cancer Control 2004; 11: 6-14.
  • 24. Bardeesy N, Depinho RA. Pancreatic cancer biology and genetics. Nat Rev Cancer 2002; 2: 897-909.
  • 25. Yeo CJ, Sohn TA, Cameron JL, et al. Periampullary adenocarcinoma: analysis of 5 year survivors. Ann Surg 1998; 227: 821-31.
  • 26. Garcea G, Dennison AR, Pattenden CJ, Neal CP, Sutton CD, Berry DB. Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature. J Pancreas 2008; 9: 99-132.
  • 27. Takai S, Satoi S, Toyokawa H, et al. Clinicopathologic evaluation after resection for ductal adenocarcinoma of the pancreas: A retrospective, single institution experience. Pancreas 2003; 26: 243-9.
  • 28. Michelassi F, Erroi F, Dawson PJ, et al. Experience with 647 consecutive tumors of the duodenum, ampulla, head of the pancreas, and distal common bile duct. Ann Surg 1989; 210: 544-56.
  • 29. Keleg S, Büchler P, Ludwig R, Büchler MW, Friess H. Invasion and metastasis in pancreatic cancer. Molecular Cancer 2003; 2: 1-7.
  • 30. Ueda M, Endo I, Nakashima M, et al. Prognostic factors after resection of pancreatic cancer. World J Surg 2009; 33: 104-10.
  • 31. Riediger H, Keck T, Wellner U, et al. F. The lymph node ratio is the strongest prognostic factor after resection of pancreatic cancer. J Gastrointest Surg 2009; 13: 1337-44.
  • 32. You DD, Lee HG, Heo JS, Choi SH, Choi DW. Prognostic factors and adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic Adenocarcinoma. J Gastrointest Surg 2009; 13: 1699-706.
  • 33. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Pancreatic section, BSG, Gut 2005; 54: v1-16.
Toplam 33 adet kaynakça vardır.

Ayrıntılar

Konular Sağlık Kurumları Yönetimi
Bölüm Özgün Makale
Yazarlar

Mehmet Zengın

Nevra Dursun

Hüsniye Esra Paşaoğlu Bu kişi benim

Oğuz Koç Bu kişi benim

Yayımlanma Tarihi 1 Haziran 2017
Yayımlandığı Sayı Yıl 2017 Cilt: 8 Sayı: 4

Kaynak Göster

APA Zengın, M., Dursun, N., Paşaoğlu, H. E., Koç, O. (2017). Pankreatik duktal adenokarsinomlar ve ampüller bölge adenokarsinomlarında HSF-1 ve P53 ekspresyonlarının prognostik faktörlerle ilişkisi. Turkish Journal of Clinics and Laboratory, 8(4), 168-174. https://doi.org/10.18663/tjcl.284388
AMA Zengın M, Dursun N, Paşaoğlu HE, Koç O. Pankreatik duktal adenokarsinomlar ve ampüller bölge adenokarsinomlarında HSF-1 ve P53 ekspresyonlarının prognostik faktörlerle ilişkisi. TJCL. Aralık 2017;8(4):168-174. doi:10.18663/tjcl.284388
Chicago Zengın, Mehmet, Nevra Dursun, Hüsniye Esra Paşaoğlu, ve Oğuz Koç. “Pankreatik Duktal Adenokarsinomlar Ve ampüller bölge adenokarsinomlarında HSF-1 Ve P53 ekspresyonlarının Prognostik faktörlerle ilişkisi”. Turkish Journal of Clinics and Laboratory 8, sy. 4 (Aralık 2017): 168-74. https://doi.org/10.18663/tjcl.284388.
EndNote Zengın M, Dursun N, Paşaoğlu HE, Koç O (01 Aralık 2017) Pankreatik duktal adenokarsinomlar ve ampüller bölge adenokarsinomlarında HSF-1 ve P53 ekspresyonlarının prognostik faktörlerle ilişkisi. Turkish Journal of Clinics and Laboratory 8 4 168–174.
IEEE M. Zengın, N. Dursun, H. E. Paşaoğlu, ve O. Koç, “Pankreatik duktal adenokarsinomlar ve ampüller bölge adenokarsinomlarında HSF-1 ve P53 ekspresyonlarının prognostik faktörlerle ilişkisi”, TJCL, c. 8, sy. 4, ss. 168–174, 2017, doi: 10.18663/tjcl.284388.
ISNAD Zengın, Mehmet vd. “Pankreatik Duktal Adenokarsinomlar Ve ampüller bölge adenokarsinomlarında HSF-1 Ve P53 ekspresyonlarının Prognostik faktörlerle ilişkisi”. Turkish Journal of Clinics and Laboratory 8/4 (Aralık 2017), 168-174. https://doi.org/10.18663/tjcl.284388.
JAMA Zengın M, Dursun N, Paşaoğlu HE, Koç O. Pankreatik duktal adenokarsinomlar ve ampüller bölge adenokarsinomlarında HSF-1 ve P53 ekspresyonlarının prognostik faktörlerle ilişkisi. TJCL. 2017;8:168–174.
MLA Zengın, Mehmet vd. “Pankreatik Duktal Adenokarsinomlar Ve ampüller bölge adenokarsinomlarında HSF-1 Ve P53 ekspresyonlarının Prognostik faktörlerle ilişkisi”. Turkish Journal of Clinics and Laboratory, c. 8, sy. 4, 2017, ss. 168-74, doi:10.18663/tjcl.284388.
Vancouver Zengın M, Dursun N, Paşaoğlu HE, Koç O. Pankreatik duktal adenokarsinomlar ve ampüller bölge adenokarsinomlarında HSF-1 ve P53 ekspresyonlarının prognostik faktörlerle ilişkisi. TJCL. 2017;8(4):168-74.


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