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Küçük Hücre Dışı Akciğer Karsinomlarında Biyolojik Davranışın Belirlenmesinde p53 ve Ki-67 Ekspresyonunun Değeri

Year 2020, Volume: 30 Issue: 4, 248 - 254, 01.12.2020

Abstract

Amaç: Akciğer karsinomlarında yapılan son çalışmalar, tümörü erken evrede tespit etme, nüks ve mortalite riskini belirleme ile hedef tedavide etkili olan klinikopatolojik faktörleri saptamak için yürütülmektedir. Bu çalışmamızda rezeke edilen küçük hücre dışı akciğer karsinom KHDAK olgularını 2015 Dünya Sağlık Örgütü DSÖ sınıflamasına göre yeniden değerlendirerek, p53 ve Ki-67'nin immünohistokimyasal ekspresyonunun klinikopatolojik parametreler ile ilişkisini ve prognostik önemini belirlemeyi amaçladık.Gereç ve Yöntem: Rezeksiyon materyallerinde KHDAK tanısı alan Evre I - III arasındaki 125 olguda retrospektif olarak klinikopatolojik özellikler cinsiyet, yaş, sigara kullanımı, tümör boyutu, plevra invazyonu, lenf nodu tutulumu, evre, sağkalım ile p53 ve Ki-67 immunhistokimyasal ekspresyonu değerlendirildi.Bulgular: p53 ekspresyonu 125 olgunun 61’inde>%10’du. Ki-67 ekspresyonunun ortalama değeri %32,9’du. Hem p53 hem de Ki-67 ekspresyonunun tümörün histolojik tipler ile ilişkisi incelendiğinde anlamlı sonuçlar bulundu p=0,036 ve p=0,000 . Ki-67’den farklı olarak p53 ekspresyonu adenokarsinom ADK alt tiplerinde derece yükseldikçe anlamlı yüksek bulundu p=0,036 . Yüksek Ki-67 ekspresyonu tümör boyutu ve evre artışı ile ilişkiliydi p=0,008 ve p=0,020 . Tek değişkenli ve çok değişkenli analizlerde prognozu etkileyen faktörler yaş ve tümörün evresi idi p=0,021 ve p=0,041 . Klinikopatolojik bulgular sağkalıma tek başına etkili değildi. Wald testi p53 ve Ki-67 ekspresyonu, sigara ve cinsiyet ile genel sağkalım arasında anlamlı bir ilişki olmadığını ortaya koymuştur.Sonuç: KHDAK’larında Ki-67 ekspresyonu büyük tümör boyutu ve ileri evre ile güçlü bir ilişkiyi göstermektedir. p53 mutasyonu skuamöz hücreli karsinomlarda ve özellikle ADK solid varyantta daha sık görülmektedir. Bununla birlikte, p53 ve Ki-67 proteinlerinin prognostik öneminin daha büyük hasta gruplarında ve uzun süreli takiplerle araştırılmasının daha anlamlı sonuçlar sunabileceği ön görülmektedir

References

  • Pelosi G, Sonzogni A, Viale G. The classification of lung carcinoma: time to change the morphology-based approa- ch. Int J Surg Pathol 2010;18:161-72.
  • Oser MG, Niederst MJ, Sequist LV, Engelman JA. Transfor- mation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. Lancet Oncol 2015;16:165–72.
  • Devesa SS, Bray F, Vizcaino AP, Parkin DM. International lung cancer trends by histologic type: male:female diffe- rences diminishing and adenocarcinoma rates rising. Int J Cancer 2005;117:294–9.
  • Varley JM, Evans DGR, Birch JM. Li-Fraumeni syndrome a molecular and clinical review. Brit J Cancer 1997;76:1-14.
  • Haris CC. Structure and function of the p53 tumor supp- ressor gene: clues for rational cancer therapeutic strategie. J Nat Can Inst 1996;88:1442-55.
  • Gerdes J, Lemke H, Baisch H, et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984;133:1710–5.
  • Ikeda G, Isaji S, Das BC, Watanabe M, Kawarada Y. Prog- nostic significance of biologic factors in squamous cell car- cinoma of the esophagus. Cancer 1999;86:1396-405.
  • Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associate. Int J Cancer 2005;68:1236-41.
  • Huisman MA, De Heer E, Grote JJ. Cholesteatoma epit- helium is characterized by increased expression of Ki-67, p53 and p21, with minimal apoptosis. Acta Otolaryngol 2003;123:377-82.7
  • Travis WD, Brambilla E, Burke Allen P, et al. World Health Organization Classification of Tumours of the Lung, Pleu- ra, Thymus and Heart. In: Geisinger K, Moreira AL, Nichol- son AG, Ramiporta R and Travis WD, ed. Tumours of the lung. Lyon International Agency for Research on Cancer Press. 2015;10-105.
  • Porebska I, Sobańska E, Kosacka M, Jankowska R. Apopto- tic regulators: P53 and survivin expression in non-small cell lung cancer. Cancer Genomics Proteomics 2010;7: 331-5.
  • Ahn HK, Jung M, Ha SY, et al. Clinical significance of Ki- 67 and p53 expression incuratively resected non-small cell lung cancer. Tumour Biol 2014;35:5735-40.
  • Tsubochi H, Sato N, Hiyama M, et al. Combined analysis of cyclooxygenase-2 expression with p53 and Ki-67 in nons- mall cell lung cancer. Ann Thorac Surg 2006;82:1198-204.
  • Shiba M, Kohno H, Kakizawa K, et al. Ki-67 immunostai- ning and other prognostic factors including tobacco smo- king in patients with resected nonsmall cell lung carcino- ma. Cancer 2000;89:1457-65.
  • Minami K, Saito Y, Imamura H, Okamura A. Prognostic sig- nificance of p53, Ki-67, VEGF and Glut-1 in resected stage I adenocarcinoma of the lung. Lung Cancer 2002;38:51-7.
  • Kumar V and Abbas KA. Robbins and Cotran Pathologic Basis of Disease. In: Aliya NH, ed. Lung. 9th ed. 2015;712- 21.
  • Travis WD, Brambilla E, Noguchi M, et al. International Association for the Study of Lung Cancer/American Tho- racic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma. J Thoracic Oncol 2011;6:244-85.
  • Soussi T, Ishioka C, Claustres M, Beroud C. Locus specific mutation data bases: pitfalls and good practice based on the p53 experience. Nature Reviews Cancer 2006;6:83–90.
  • Olivier M, Hollstein M, Hainaut P. TP53 mutations in hu- man cancers: origins, consequences and clinical use. Cold Spring Harb Perspect in Biol 2010;1:2.
  • Robles AI, Harris CC. Clinical outcomes and correlates of TP53 mutations and cancer. Cold Spring Harb Perspect in Biol 2010;3:2.
  • Miller CW, Simon K, Aslo A, et al. p53 Mutations in human lung tumors. Cancer Research 1992;52:1695–8.
  • Reichel MB, Ohgaki H, Petersen I, Kleihues P. p53 mutati- ons in primary human lung tumors and their metastases. Mol Carcinog 1994;9:105–9.
  • Kosaka T, Yatabe Y, Onozato R, Kuwano H, Mitsudomi T. Prognostic implication of EGFR, KRAS, and TP53 gene mu- tations in a large cohort of Japanese patients with surgically treated lung adenocarcinoma. J Thorac Oncol 2009;4:22-9.
  • Mogi A, Kuwano H. TP53 mutations in non-small cell lung cancer. J Biomed Biotechnol 2011;583929.
  • Hommura F, Akita HD, Mishina T, et al. Prognostic signi- ficance of p27KIP1 protein and ki-67 growth fraction in non-small cell lung cancers. Clin Cancer Res 2000; 6: 4073.
  • Martin B, Paesmans M, Mascaux C, et al. Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis. British Journal of Cancer 2004;91:2018–25.
  • Pence JC, Kerns BJ, Dodge RK, Iglehart JD. Prognostic sig- nificance of the proliferation index in surgically resected non-small-cell lung cancer. Arch Surg 1993;128:1382-90.
  • Radovic S, Babic M, Doric M, et al. Non-small cell lung car- cınoma: cyclın D1, bcl-2, p53, Ki-67 and HER-2 proteins expressıon in resected tumors. Bosnıan Journal Of Basıc Medıcal Scıences 2007;7:205-11.
  • Wen S, Zhou W, Li CM, et al. Ki-67 as a prognostic marker in early-stage non-small cell lung cancer in Asian patients: a meta-analysis of published studies involving 32 studies. BMC Cancer 2015;15(520).
  • Nguyen VN, Mirejovsky P, Miejovsky T, Melinova L, Mandys V. Expression of cyclin D1, Ki-67 and PCNA in non-small cell lung cancer: prognostic significance and comparison with p53 and bcl-2. Acta Histochem 2000;102:323-38.
  • Saber S, Salehian P. P53 and Ki-67 biomarkers as prognos- tic factors of non-small cell lung carcınoma. Acta Medica Iranica 2005;43:127-30.
  • Mİrkve O, Halvorsen OJ, Skjaerven R, et al. Prognostic sig- nificance of p53 protein expression and DNA ploidy in sur- gically treated non-small cell lung carcinomas. Anticancer Res 1993;13:571-8.
  • Lee JS, Yoon A, Kalapurakal SK, et al. Expression of p53 on- coprotein in non-small-cell lung cancer: a favorable prog- nostic factor. J Clin Oncol 1995;13:1893-903.
  • Steels E, Paesmans M, Berghmans T, et al. Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J 2001;18:705-19.
  • Huncharek M, Kupelnick B, Geschwind JF, Tagahashi T. Prognostic significance of p53 mutations in non-small cell lung cancer: a meta-analysis of 829 cases from eight publis- hed studies. Cancer Lett 2000;153:219-26.
  • Han JY, Lee GK, Jang DH, Association of p53 codon 72 pol- ymorphism and MDM2 SNP309 with clinical outcome of advanced non-small cell lung cancer. Cancer 2008;113:799– 807.
  • Joerger M, Dejong D, Burylo A, et al. Tubulin, BRCA1, ERCC1, Abraxas, RAP80 mRNA expression, p53/p21 im- munohistochemistry and clinical outcome in patients with advanced non small-cell lung cancer receiving first-li- ne platinum-gemcitabine chemotherapy. Lung Cancer 2011;74:310-7.

The value of p53 and ki-67 expression in determining biological behavior in non-small cell lung carcinomas

Year 2020, Volume: 30 Issue: 4, 248 - 254, 01.12.2020

Abstract

Objective: Recent studies of lung carcinomas have been conducted to detect tumors in early-stage disease, to determine the risk of recurrence and mortality, and to determine the clinicopathological factors that are effective in targeted treatment. The aim of this study was to determine the prognostic value and association of immunohistochemical expression of p53 and Ki-67 with clinicopathological parameters in non-small cell lung carcinoma NSCLC and their variants. Material and Methods: Clinicopathological features and p53 and Ki-67 expression were evaluated retrospectively in 125 patients diagnosed with NSCLC based on lung resection materials. The resected materials were assessed according to the 2015 World Health Organization WHO classification.Results: p53 expression was > 10% in 61 of 125 cases. The average value of Ki-67 expression was 32.9%. Both p53 and Ki-67 expression were significantly associated with the histological tumor type p=0.036 and p=0.000, respectively . p53 expression was significantly elevated in adenocarcinoma ADC subtypes when the stage increased p=0.036 . High Ki-67 expression was associated with tumor size and stage increase p=0.008 and p=0.020, respectively . Factors affecting the prognosis in univariate-multivariate analyses were age and tumor stage p=0.021 and p=0.041, respectively .Conclusion: Ki-67 expression in NSCLC shows a strong association with large tumor size and advanced stage.p53 mutation is more common in squamous cell carcinoma and especially in ADC solid variant. However, it is predicted that the prognostic significance of p53 and Ki-67 proteins may provide more meaningful results in larger patient groups and long-term follow-up

References

  • Pelosi G, Sonzogni A, Viale G. The classification of lung carcinoma: time to change the morphology-based approa- ch. Int J Surg Pathol 2010;18:161-72.
  • Oser MG, Niederst MJ, Sequist LV, Engelman JA. Transfor- mation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. Lancet Oncol 2015;16:165–72.
  • Devesa SS, Bray F, Vizcaino AP, Parkin DM. International lung cancer trends by histologic type: male:female diffe- rences diminishing and adenocarcinoma rates rising. Int J Cancer 2005;117:294–9.
  • Varley JM, Evans DGR, Birch JM. Li-Fraumeni syndrome a molecular and clinical review. Brit J Cancer 1997;76:1-14.
  • Haris CC. Structure and function of the p53 tumor supp- ressor gene: clues for rational cancer therapeutic strategie. J Nat Can Inst 1996;88:1442-55.
  • Gerdes J, Lemke H, Baisch H, et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984;133:1710–5.
  • Ikeda G, Isaji S, Das BC, Watanabe M, Kawarada Y. Prog- nostic significance of biologic factors in squamous cell car- cinoma of the esophagus. Cancer 1999;86:1396-405.
  • Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associate. Int J Cancer 2005;68:1236-41.
  • Huisman MA, De Heer E, Grote JJ. Cholesteatoma epit- helium is characterized by increased expression of Ki-67, p53 and p21, with minimal apoptosis. Acta Otolaryngol 2003;123:377-82.7
  • Travis WD, Brambilla E, Burke Allen P, et al. World Health Organization Classification of Tumours of the Lung, Pleu- ra, Thymus and Heart. In: Geisinger K, Moreira AL, Nichol- son AG, Ramiporta R and Travis WD, ed. Tumours of the lung. Lyon International Agency for Research on Cancer Press. 2015;10-105.
  • Porebska I, Sobańska E, Kosacka M, Jankowska R. Apopto- tic regulators: P53 and survivin expression in non-small cell lung cancer. Cancer Genomics Proteomics 2010;7: 331-5.
  • Ahn HK, Jung M, Ha SY, et al. Clinical significance of Ki- 67 and p53 expression incuratively resected non-small cell lung cancer. Tumour Biol 2014;35:5735-40.
  • Tsubochi H, Sato N, Hiyama M, et al. Combined analysis of cyclooxygenase-2 expression with p53 and Ki-67 in nons- mall cell lung cancer. Ann Thorac Surg 2006;82:1198-204.
  • Shiba M, Kohno H, Kakizawa K, et al. Ki-67 immunostai- ning and other prognostic factors including tobacco smo- king in patients with resected nonsmall cell lung carcino- ma. Cancer 2000;89:1457-65.
  • Minami K, Saito Y, Imamura H, Okamura A. Prognostic sig- nificance of p53, Ki-67, VEGF and Glut-1 in resected stage I adenocarcinoma of the lung. Lung Cancer 2002;38:51-7.
  • Kumar V and Abbas KA. Robbins and Cotran Pathologic Basis of Disease. In: Aliya NH, ed. Lung. 9th ed. 2015;712- 21.
  • Travis WD, Brambilla E, Noguchi M, et al. International Association for the Study of Lung Cancer/American Tho- racic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma. J Thoracic Oncol 2011;6:244-85.
  • Soussi T, Ishioka C, Claustres M, Beroud C. Locus specific mutation data bases: pitfalls and good practice based on the p53 experience. Nature Reviews Cancer 2006;6:83–90.
  • Olivier M, Hollstein M, Hainaut P. TP53 mutations in hu- man cancers: origins, consequences and clinical use. Cold Spring Harb Perspect in Biol 2010;1:2.
  • Robles AI, Harris CC. Clinical outcomes and correlates of TP53 mutations and cancer. Cold Spring Harb Perspect in Biol 2010;3:2.
  • Miller CW, Simon K, Aslo A, et al. p53 Mutations in human lung tumors. Cancer Research 1992;52:1695–8.
  • Reichel MB, Ohgaki H, Petersen I, Kleihues P. p53 mutati- ons in primary human lung tumors and their metastases. Mol Carcinog 1994;9:105–9.
  • Kosaka T, Yatabe Y, Onozato R, Kuwano H, Mitsudomi T. Prognostic implication of EGFR, KRAS, and TP53 gene mu- tations in a large cohort of Japanese patients with surgically treated lung adenocarcinoma. J Thorac Oncol 2009;4:22-9.
  • Mogi A, Kuwano H. TP53 mutations in non-small cell lung cancer. J Biomed Biotechnol 2011;583929.
  • Hommura F, Akita HD, Mishina T, et al. Prognostic signi- ficance of p27KIP1 protein and ki-67 growth fraction in non-small cell lung cancers. Clin Cancer Res 2000; 6: 4073.
  • Martin B, Paesmans M, Mascaux C, et al. Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis. British Journal of Cancer 2004;91:2018–25.
  • Pence JC, Kerns BJ, Dodge RK, Iglehart JD. Prognostic sig- nificance of the proliferation index in surgically resected non-small-cell lung cancer. Arch Surg 1993;128:1382-90.
  • Radovic S, Babic M, Doric M, et al. Non-small cell lung car- cınoma: cyclın D1, bcl-2, p53, Ki-67 and HER-2 proteins expressıon in resected tumors. Bosnıan Journal Of Basıc Medıcal Scıences 2007;7:205-11.
  • Wen S, Zhou W, Li CM, et al. Ki-67 as a prognostic marker in early-stage non-small cell lung cancer in Asian patients: a meta-analysis of published studies involving 32 studies. BMC Cancer 2015;15(520).
  • Nguyen VN, Mirejovsky P, Miejovsky T, Melinova L, Mandys V. Expression of cyclin D1, Ki-67 and PCNA in non-small cell lung cancer: prognostic significance and comparison with p53 and bcl-2. Acta Histochem 2000;102:323-38.
  • Saber S, Salehian P. P53 and Ki-67 biomarkers as prognos- tic factors of non-small cell lung carcınoma. Acta Medica Iranica 2005;43:127-30.
  • Mİrkve O, Halvorsen OJ, Skjaerven R, et al. Prognostic sig- nificance of p53 protein expression and DNA ploidy in sur- gically treated non-small cell lung carcinomas. Anticancer Res 1993;13:571-8.
  • Lee JS, Yoon A, Kalapurakal SK, et al. Expression of p53 on- coprotein in non-small-cell lung cancer: a favorable prog- nostic factor. J Clin Oncol 1995;13:1893-903.
  • Steels E, Paesmans M, Berghmans T, et al. Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J 2001;18:705-19.
  • Huncharek M, Kupelnick B, Geschwind JF, Tagahashi T. Prognostic significance of p53 mutations in non-small cell lung cancer: a meta-analysis of 829 cases from eight publis- hed studies. Cancer Lett 2000;153:219-26.
  • Han JY, Lee GK, Jang DH, Association of p53 codon 72 pol- ymorphism and MDM2 SNP309 with clinical outcome of advanced non-small cell lung cancer. Cancer 2008;113:799– 807.
  • Joerger M, Dejong D, Burylo A, et al. Tubulin, BRCA1, ERCC1, Abraxas, RAP80 mRNA expression, p53/p21 im- munohistochemistry and clinical outcome in patients with advanced non small-cell lung cancer receiving first-li- ne platinum-gemcitabine chemotherapy. Lung Cancer 2011;74:310-7.
There are 37 citations in total.

Details

Primary Language Turkish
Journal Section Original Article
Authors

Tuğba Günler This is me

Pınar Karabağlı This is me

Zeliha Esin Çelik This is me

Ceyhan Uğurluoğlu This is me

Publication Date December 1, 2020
Published in Issue Year 2020 Volume: 30 Issue: 4

Cite

Vancouver Günler T, Karabağlı P, Çelik ZE, Uğurluoğlu C. Küçük Hücre Dışı Akciğer Karsinomlarında Biyolojik Davranışın Belirlenmesinde p53 ve Ki-67 Ekspresyonunun Değeri. Genel Tıp Derg. 2020;30(4):248-54.

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