Abstract
Amaç: Akciğer kanseri dünya genelinde kansere bağlı
ölümlerin önde gelen nedenidir. Tanısal cihazlar ve teknolojik gelişmelere
bağlı tedavi seçeneklerinde ilerlemeye rağmen, akciğer kanseri hastalarında
genel mortalite oranı hala yüksektir. Akciğer kanseri hastalarında sağkalım
oranları, özellikle ilerlemiş inoperabl hastalıkta, immunoterapi gibi yeni
tedavi seçeneklerine rağmen düşüktür. p53, kanser hastalarının %60-70’inde mutasyona
uğramaktadır ve bu nedenle son zamanlarda yapılan çalışmalar göstermektedir ki,
serum anti-p53 antikorunun, over, özefagus, meme ve akciğer kanseri gibi bazı
kanser türlerinin dedekte edilmesinde biyobelirteç olarak dikkate alınabilir.
Bu çalışmada, akciğer kanseri hastalarında, serum anti-p53antikor düzeylerinin
tanısal ve prognostik önemini araştırmayı amaçladık.
Yöntem: Çalışmaya
akciğer kanseri (AK) tanısı nedeniyle evreleme için 18F-FDG-PET / BT
görüntüleme amacı ile bölümümüze sevk edilen hastalar, toraks BT’sinde şüpheli
pulmoner nodül olup, patolojik FDG birikimi göstermeyen hastalar (NAPN= Non-avid FDG gösteren
pulmoner nodül) ve sağlıklı gönüllüler dahil edildi. Serum anti-p53antikor
düzeyleri tüm hastalarda ELISA yöntemi ile ölçüldü. Hastaların ortalama takip
süresi 13 ay idi.
Bulgular: Çalışmaya toplam 65 AK hastası (58E/7K), 47 NAPN
hastası (20E/27K) ve 34 sağlıklı gönüllü (26E /8K) dahil edildi. Ortalama serum
anti-p53antikor seviyeleri AK hastalarında 3.4ng/mL, NAPN hastalarında 3.77ng
/mL, sağlıklı gönüllülerde 3.07 ng/ mL idi. AK hastaları ile NAPN hastaları arasında
serum anti-p53antikor düzeyi için istatistiksel olarak anlamlı fark yoktu (p =
0.678). Hatta, hastalar
ve sağlıklı gönüllüler arasında serum anti-p53Ab düzeyi için istatistiksel
olarak anlamlı fark yoktu (p = 0.377). Hastaların iki yıllık medyan sağkalımı
14 aydı. Hastaların
sağkalım hızında, serum anti-p53Ab düzeyinin > 3.4 ng/ mL veya ≤3.4 ng/ mL olmasının herhangi bir etkisinin
olmadığı bulundu (p = 0.652).
Sonuç: Anti-p53antikoru,
karsinogeneziste çok önemli olmasına rağmen, serum anti-p53antikor düzeyinin
akciğer kanseri tanısında ve sağkalım oranlarında tek başına önemli olmadığını düşünüyoruz. Karsinogeneziste
birden fazla faktör vardır ve bu durumun nedeni olabilir. Akciğer kanseri
hastalarının teşhisi için serum anti-p53antikor düzeylerinin bilinen bir katof
değeri yoktur. Bu nedenle, bu
antikorun tümör spesifikliği olmadığını ve serum anti-p53antikor düzeyinin
akciğer kanseri taraması için uygun olmadığını düşünüyoruz.
Keywords
References
- 1- Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010; 60:277-300. Erratum in, CA Cancer J Clin. 2011; 61: 133-4.
- 2- Huang W, Zhou T, Ma L, Sun H, Gong H, Wang J, Yu J, Li B. Standard uptake value and metabolic tumor volume of ¹⁸F-FDG PET/CT predict short-term outcome early in the course of chemoradiotherapy in advanced non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2011; 38: 1628-35.
- 3- National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011,4; 365: 395-409.
- 4- Schaarschmidt BM, Grueneisen J, Metzenmacher M, Gomez B, Gauler T, Roesel C, Heusch P, Ruhlmann V, Umutlu L, Antoch G, Buchbender C. Thoracic staging with 18F-FDG PET/MR in non-small cell lung cancer - does it change therapeutic decisions in comparison to 18F-FDG PET/CT? Eur Radiol 2016. doi: 10.1007/s00330-016-4397-0.
- 5- Kitajima K, Doi H, Kanda T, Yamane T, Tsujikawa T, Kaida H, Tamaki Y, Kuribayashi K. Present and future roles of FDG-PET/CT imaging in the management of lung cancer. Jpn J Radiol 2016; 34: 387-99.
- 6- Park S, Lee E, Rhee S, Cho J, Choi S, Lee S, Eo JS, Pahk K, Choe JG, Kim S. Correlation between Semi-Quantitative (18) F-FDG PET/CT Parameters and Ki-67 Expression in Small Cell Lung Cancer. Nucl Med Mol Imaging 2016; 50: 24-30.
- 7- Woodard KM, Chapman CJ. Lung cancer - can autoantibodies provide an aid to diagnosis? Expert Opin Med Diagn 2008; 2: 911-23.
- 8- Gao RJ, Bao HZ, Yang Q, Cong Q, Song JN, Wang L. The presence of serum anti-p53 antibodies from patients with invasive ductal carcinoma of breast: correlation to other clinical and biological parameters. Breast Cancer Res Treat 2005; 93: 111-5.
- 9- Wu M, Mao C, Chen Q, Cu XW, Zhang WS. Serum p53 protein and anti-p53 antibodies are associated with increased cancer risk: a case-control study of 569 patients and 879 healthy controls. Mol Biol Rep 2010; 37: 339-43.
- 10- Fernández Madrid F. Autoantibodies in breast cancer sera: candidate biomarkers and reporters of tumorigenesis. Cancer Lett 2005,18; 230: 187-98.
- 11- Garziera M, Montico M, Bidoli E, Scalone S, Sorio R, Giorda G, Lucia E, Toffoli G. Prognostic Role of Serum Antibody Immunity to p53 Oncogenic Protein in Ovarian Cancer: A Systematic Review and a Meta-Analysis. PLoS One 2015, 9; 10: e0140351.
- 12- Zhang H, Xia J, Wang K, Zhang J. Serum autoantibodies in the early detection of esophageal cancer: a systematic review. Tumour Biol 2015; 36: 95-109.
- 13- Healey GF, Lam S, Boyle P, Hamilton-Fairley G, Peek LJ, Robertson JF. Signal stratification of autoantibody levels in serum samples and its application to the early detection of lung cancer. J Thorac Dis 2013; 5: 618-25.
- 14- Li Y, Karjalainen A, Koskinen H, Hemminki K, Vainio H, Shnaidman M, Ying Z, Pukkala E, Brandt-Rauf PW. p53 autoantibodies predict subsequent development of cancer. Int J Cancer 2005, 10;114: 157-60.
- 15- Lei QQ, Liu JW, Zheng H. Potential role of anti-p53 antibody in diagnosis of lung cancer: evidence from a bivariate meta-analysis. Eur Rev Med Pharmacol Sci 2013; 17: 3012-8
- 16- Mattioni M, Chinzari P, Soddu S, Strigari L, Cilenti V, Mastropasqua E. Serum p53 antibody detection in patients with impaired lung function. BMC Cancer 2013; 6: 13:62.
- 17- Kumar S, Mohan A, Guleria R. Prognostic implications of circulating anti-p53 antibodies in lung cancer--a review. Eur J Cancer Care (Engl) 2009; 18: 248-54.
- 18- Ciancio N, Galasso MG, Campisi R, Bivona L, Migliore M, Di Maria GU. Prognostic value of p53 and Ki67 expression in fiberoptic bronchial biopsies of patients with non small cell lung cancer. Multidiscip Respir Med 2012; 14: 7: 29.
- 19- Lai CL, Tsai CM, Tsai TT, Kuo BI, Chang KT, Fu HT, Perng RP, Chen JY. Presence of serum anti-p53 antibodies is associated with pleural effusion and poor prognosis in lung cancer patients. Clin Cancer Res 1998; 4: 3025-30.
- 20- Winter SF, Minna JD, Johnson BE, Takahashi T, Gazdar AF, Carbone DP. Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation. Cancer Res 1992, 1; 52: 4168-74.
- 21- Zalcman G, Trédaniel J, Schlichtholz B, Urban T, Milleron B, Lubin R, Meignin V, Couderc LJ, Hirsch A, Soussi T. Prognostic significance of serum p53 antibodies in patients with limited-stage small cell lung cancer. Int J Cancer 2000, 20; 89: 81-6.
- 22- Yu DH, Li JH, Wang YC, Xu JG, Pan PT, Wang L. Serum anti-p53 antibody detection in carcinomas and the predictive values of serum p53 antibodies, carcino-embryonic antigen and carbohydrate antigen 12-5 in the neoadjuvant chemotherapy treatment for III stage non-small cell lung cancer patients. Clin Chim Acta 2011,12; 412: 930-5.
- 23- Duan XY, Wang W, Wang JS, Shang J, Gao JG, Guo YM. Fluorodeoxyglucose positron emission tomography and chemotherapy-related tumor marker expression in non-small cell lung cancer. BMC Cancer 2013,15; 13: 546.
- 24- Nakamura H, Hirata T, Kitamura H, Nishikawa J. Correlation of the standardized uptake value in FDG-PET with the expression level of cell-cycle-related molecular biomarkers in resected non-small cell lung cancers. Ann Thorac Cardiovasc Surg 2009; 15: 304-10.
- 25- Hasbek Z, Doğan OT, Sarı I, Yücel B, Şeker MM, Turgut B, Berk S, Siliğ Y. The Diagnostic Value of the Correlation between Serum Anti-p53 Antibody and Positron Emission Tomography Parameters in Lung Cancer. Mol Imaging Radionucl Ther 2016, 5; 25: 107-113.
- 26- Koumenis C, Alarcon R, Hammond E, Sutphin P, Hoffman W, Murphy M, Derr J, Taya Y, Lowe SW, Kastan M, Giaccia A. Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol 2001; 21: 1297-310.
- 27- van Baardwijk A, Dooms C, van Suylen RJ, Verbeken E, Hochstenbag M, Dehing-Oberije C, Rupa D, Pastorekova S, Stroobants S, Buell U, Lambin P, Vansteenkiste J, De Ruysscher D. The maximum uptake of (18)F-deoxyglucose on positron emission tomography scan correlates with survival, hypoxia inducible factor-1alpha and GLUT-1 in non-small cell lung cancer. Eur J Cancer 2007; 43: 1392-8.
Abstract
Objective: Lung cancer is the leading cause
of cancer-related deaths worldwide. Despite advancement in diagnostic tools and
treatment options with technological developments, overall mortality rates in
lung cancer patients remains high. Survival rates in lung cancer patients is
low especially in advanced diseased inoperable patients in spite of new
treatment options like immunotherapy. p53 is mutated in 60-70% of cancer
patients and for this reason has been extensively studied recent researches suggest that serum
anti-p53Ab can be considered as biomarkers to detect many types of cancers; as
ovarian cancer, esophageal cancer, breast cancer and lung cancer. In this study
we aimed that are there any diagnostic and prognostic importance of serum
anti-p53Ab levels in lung cancer patients.
Method: Patients were included who were
referred to our department with the purpose of 18F-FDG-PET/CT
imaging for staging due to lung cancer diagnosis (LC) and patients who were
performed 18F-FDG-PET/CT for diagnosis in the cause of the suspected
pulmonary nodule in thorax CT but not detected pathologic FDG accumulation
(NAPN=pulmonary nodule with non-avid-FDG) and healthy volunteers. Serum
anti-p53Ab levels were measured with ELISA method in the all patients. Mean
follow up time of patients were 13 months.
Results: A total of 65 LC patients
(58M/7F), 47 patients with NAPN (20M/27F), and a total of 34 healthy volunteers
(26M/8F) were included in this study. Median serum anti-p53Ab levels are
3.4ng/mL in LC patients, 3.77ng/mL in NAPN patients, 3.07ng/mL in healthy
volunteers. There is no statistically significant difference for serum
anti-p53Ab level between LC patients and NAPN patients (p=0.678). Moreover there is no statistically significant difference
for serum anti-p53Ab level between patients and healthy volunteers (p=0.377). Two-year median survival of
patients was 14 month. It has been found that there is no effect of serum
anti-p53Ab level whether >3.4 or ≤3.4 on the patient survival rate (p=0.652).
Conclusions: Even though
anti-p53Ab is very important in carcinogenesis, we think that serum anti-p53Ab
level by itself is not important in lung cancer diagnosis and survival rates.
There are multiple factors in carcinogenesis and this may be the reason of this
situation. There is no known cut off value of serum anti-p53 Ab levels for
diagnosis of lung cancer patients. Therefore we think that this antibody is not
tumor spesific and serum anti-p53 Ab level measurement is not appropriate for
lung cancer screening.
Keywords
References
- 1- Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010; 60:277-300. Erratum in, CA Cancer J Clin. 2011; 61: 133-4.
- 2- Huang W, Zhou T, Ma L, Sun H, Gong H, Wang J, Yu J, Li B. Standard uptake value and metabolic tumor volume of ¹⁸F-FDG PET/CT predict short-term outcome early in the course of chemoradiotherapy in advanced non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2011; 38: 1628-35.
- 3- National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011,4; 365: 395-409.
- 4- Schaarschmidt BM, Grueneisen J, Metzenmacher M, Gomez B, Gauler T, Roesel C, Heusch P, Ruhlmann V, Umutlu L, Antoch G, Buchbender C. Thoracic staging with 18F-FDG PET/MR in non-small cell lung cancer - does it change therapeutic decisions in comparison to 18F-FDG PET/CT? Eur Radiol 2016. doi: 10.1007/s00330-016-4397-0.
- 5- Kitajima K, Doi H, Kanda T, Yamane T, Tsujikawa T, Kaida H, Tamaki Y, Kuribayashi K. Present and future roles of FDG-PET/CT imaging in the management of lung cancer. Jpn J Radiol 2016; 34: 387-99.
- 6- Park S, Lee E, Rhee S, Cho J, Choi S, Lee S, Eo JS, Pahk K, Choe JG, Kim S. Correlation between Semi-Quantitative (18) F-FDG PET/CT Parameters and Ki-67 Expression in Small Cell Lung Cancer. Nucl Med Mol Imaging 2016; 50: 24-30.
- 7- Woodard KM, Chapman CJ. Lung cancer - can autoantibodies provide an aid to diagnosis? Expert Opin Med Diagn 2008; 2: 911-23.
- 8- Gao RJ, Bao HZ, Yang Q, Cong Q, Song JN, Wang L. The presence of serum anti-p53 antibodies from patients with invasive ductal carcinoma of breast: correlation to other clinical and biological parameters. Breast Cancer Res Treat 2005; 93: 111-5.
- 9- Wu M, Mao C, Chen Q, Cu XW, Zhang WS. Serum p53 protein and anti-p53 antibodies are associated with increased cancer risk: a case-control study of 569 patients and 879 healthy controls. Mol Biol Rep 2010; 37: 339-43.
- 10- Fernández Madrid F. Autoantibodies in breast cancer sera: candidate biomarkers and reporters of tumorigenesis. Cancer Lett 2005,18; 230: 187-98.
- 11- Garziera M, Montico M, Bidoli E, Scalone S, Sorio R, Giorda G, Lucia E, Toffoli G. Prognostic Role of Serum Antibody Immunity to p53 Oncogenic Protein in Ovarian Cancer: A Systematic Review and a Meta-Analysis. PLoS One 2015, 9; 10: e0140351.
- 12- Zhang H, Xia J, Wang K, Zhang J. Serum autoantibodies in the early detection of esophageal cancer: a systematic review. Tumour Biol 2015; 36: 95-109.
- 13- Healey GF, Lam S, Boyle P, Hamilton-Fairley G, Peek LJ, Robertson JF. Signal stratification of autoantibody levels in serum samples and its application to the early detection of lung cancer. J Thorac Dis 2013; 5: 618-25.
- 14- Li Y, Karjalainen A, Koskinen H, Hemminki K, Vainio H, Shnaidman M, Ying Z, Pukkala E, Brandt-Rauf PW. p53 autoantibodies predict subsequent development of cancer. Int J Cancer 2005, 10;114: 157-60.
- 15- Lei QQ, Liu JW, Zheng H. Potential role of anti-p53 antibody in diagnosis of lung cancer: evidence from a bivariate meta-analysis. Eur Rev Med Pharmacol Sci 2013; 17: 3012-8
- 16- Mattioni M, Chinzari P, Soddu S, Strigari L, Cilenti V, Mastropasqua E. Serum p53 antibody detection in patients with impaired lung function. BMC Cancer 2013; 6: 13:62.
- 17- Kumar S, Mohan A, Guleria R. Prognostic implications of circulating anti-p53 antibodies in lung cancer--a review. Eur J Cancer Care (Engl) 2009; 18: 248-54.
- 18- Ciancio N, Galasso MG, Campisi R, Bivona L, Migliore M, Di Maria GU. Prognostic value of p53 and Ki67 expression in fiberoptic bronchial biopsies of patients with non small cell lung cancer. Multidiscip Respir Med 2012; 14: 7: 29.
- 19- Lai CL, Tsai CM, Tsai TT, Kuo BI, Chang KT, Fu HT, Perng RP, Chen JY. Presence of serum anti-p53 antibodies is associated with pleural effusion and poor prognosis in lung cancer patients. Clin Cancer Res 1998; 4: 3025-30.
- 20- Winter SF, Minna JD, Johnson BE, Takahashi T, Gazdar AF, Carbone DP. Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation. Cancer Res 1992, 1; 52: 4168-74.
- 21- Zalcman G, Trédaniel J, Schlichtholz B, Urban T, Milleron B, Lubin R, Meignin V, Couderc LJ, Hirsch A, Soussi T. Prognostic significance of serum p53 antibodies in patients with limited-stage small cell lung cancer. Int J Cancer 2000, 20; 89: 81-6.
- 22- Yu DH, Li JH, Wang YC, Xu JG, Pan PT, Wang L. Serum anti-p53 antibody detection in carcinomas and the predictive values of serum p53 antibodies, carcino-embryonic antigen and carbohydrate antigen 12-5 in the neoadjuvant chemotherapy treatment for III stage non-small cell lung cancer patients. Clin Chim Acta 2011,12; 412: 930-5.
- 23- Duan XY, Wang W, Wang JS, Shang J, Gao JG, Guo YM. Fluorodeoxyglucose positron emission tomography and chemotherapy-related tumor marker expression in non-small cell lung cancer. BMC Cancer 2013,15; 13: 546.
- 24- Nakamura H, Hirata T, Kitamura H, Nishikawa J. Correlation of the standardized uptake value in FDG-PET with the expression level of cell-cycle-related molecular biomarkers in resected non-small cell lung cancers. Ann Thorac Cardiovasc Surg 2009; 15: 304-10.
- 25- Hasbek Z, Doğan OT, Sarı I, Yücel B, Şeker MM, Turgut B, Berk S, Siliğ Y. The Diagnostic Value of the Correlation between Serum Anti-p53 Antibody and Positron Emission Tomography Parameters in Lung Cancer. Mol Imaging Radionucl Ther 2016, 5; 25: 107-113.
- 26- Koumenis C, Alarcon R, Hammond E, Sutphin P, Hoffman W, Murphy M, Derr J, Taya Y, Lowe SW, Kastan M, Giaccia A. Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol 2001; 21: 1297-310.
- 27- van Baardwijk A, Dooms C, van Suylen RJ, Verbeken E, Hochstenbag M, Dehing-Oberije C, Rupa D, Pastorekova S, Stroobants S, Buell U, Lambin P, Vansteenkiste J, De Ruysscher D. The maximum uptake of (18)F-deoxyglucose on positron emission tomography scan correlates with survival, hypoxia inducible factor-1alpha and GLUT-1 in non-small cell lung cancer. Eur J Cancer 2007; 43: 1392-8.
Details
| Subjects | Health Care Administration |
|---|---|
| Journal Section | Medical Science Research Articles |
| Authors | |
| Publication Date | September 19, 2017 |
| Acceptance Date | July 24, 2017 |
| Published in Issue | Year 2017 |