Influence of biological markers on overall survival in surgically treated patients with non-small cell lung cancer

  • Olivera Lončarević Military Medical Academy, P ulmonology Clinic, Belgrade, Serbia
  • Slobodan Lončarević Military Medical Academy, Maxillofacial Surgery Clinic Belgrade, Serbia
  • Berislav Vekić Clinical Center “Dr. Dragiša Mišović“, Department of Surgery, Belgrade, Serbia
  • Leonida Djukanović BELhospice – Center for Palliative Care and Palliative Medicine, Belgrade, Serbia
  • Jelena Vuković Military Medical Academy, Pulmonology Clinic, Belgrade, Serbia
  • Nemanja Rančić Military Medical Academy, Center for Clinical Pharmacology, Belgrade, Serbia
Keywords: biomarkers, carcinoma, non-small-cell lung, immunohistochemistry, survival, neoplasm staging, surgical procedures, operative

Abstract


Background/Aim. Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors and a leading cause of cancer-related deaths. The aim of this study was to assess the impact of biological markers on the overall survival rate in surgically treated NSCLC patients who received adjuvant chemotherapy and/or radiation therapy. Methods. This retrospective case series study included patients with NSCLC treated in the period between 2008 and 2017 at the Pulmonology Clinic and the Clinic for Chest Surgery, Military Medical Academy, Belgrade, Serbia. The survival analysis performed was based on immunohistological findings, histology type, and tumor, node, metastasis (TNM) stages. Results. The mortality rate was higher in the adenocarcinoma patient group compared to the squamous cell carcinoma group, albeit without statistical significance (58.3% vs. 31.2%, respectively; p = 0.175). Overall survival was shorter in the adenocarcinoma patient group compared to the squamous cell carcinoma group by approximately 750 days. Likewise, overall survival was shorter in the adenocarcinoma patient group compared to the squamous cell carcinoma group for CD31 positive (p = 0.029), p-63 positive (p = 0.049), MMP-9 positive (p = 0.032), and matrix metalloproteinase (MMP)-2 positive patients (p = 0.016). Conclusion. Adenocarcinoma is a more aggressive cancer type compared to squamous cell carcinoma with shorter overall survival. Our research showed a poorer overall survival in the adenocarcinoma group of patients compared to the squamous cell carcinoma group in CD31, p-63, MMP-9, and MMP-2 positive patients.

References

org/ [homepage on the Internet]. American Cancer Society. Cancer facts and figures 2016. Available from: http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf[cited 2019 June 13].

Fenchel K, Sellmann L, Dempke WC. Overall survival in non-small cell lung cancer-what is clinically meaningful? Transl Lung Cancer Res. 2016; 5(1): 115−9.

Global Burden of Disease Cancer Collaboration. Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Dicker DJ, et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol 2017; 3(4): 524−48.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008; 58(2): 71−96.

Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC. World Health Organization classification of tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press; 2004. 

Milašinović G. Nationality guidelines of good clinical practice: lung cancer. Belgrade: National Expert Commission for the development and implementation of good clinical practice guide; 2012. Available from: http://www.zdravlje.gov.rs/downloads/2011/Decembar/Vodici/Vodic%20za%20dijagnostikovanje%20i%20lecenje%20karcinoma%20pluca.pdf[cited 2019 June 13]. (Serbian)

Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 2008; 83(5): 584−94.

Lim W, Ridge CA, Nicholson AG, Mirsadraee S. The 8th lung cancer TNM classification and clinical staging system: review of the changes and clinical implications. Quant Imaging Med Surg 2018; 8(7): 709−18.

Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004; 350(4): 351−60.

Rowell NP, Williams CJ. Radical radiotherapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (medically inoperable): a systematic review. Thorax 2001; 56(8): 628−38.

Thunnissen E, van der Oord K, den Bakker M. Prognostic and predictive biomarkers in lung cancer. A review. Virchows Arch 2014; 464(3): 347−58.

Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W, et al. SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations). Bethesede, MD: National Cancer Institute. 2009. Available from: http://seer.cancer.gov/csr/1975_2009_pops09/[cited 2019 June 13].

Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997; 111(6): 1710−7.

Durm G, Hanna N. Second-Line Chemotherapy and Beyond for Non-Small Cell Lung Cancer. Hematol OncolClin North Am 2017; 31(1): 71−81.

Heist RS. First-Line Systemic Therapy for Non-Small Cell Lung Cancer. Hematol Oncol Clin North Am 2017; 31(1): 59−70.

Tam K, Daly M, Kelly K. Treatment of Locally Advanced Non-Small Cell Lung Cancer. Hematol Oncol Clin North Am 2017; 31(1): 45−57.

Chuang JC, Liang Y, Wakelee HA. Neoadjuvant and Adjuvant Therapy for Non-Small Cell Lung Cancer. Hematol Oncol Clin North Am. 2017; 31(1): 31−44.

Park SJ, More S, Murtuza A, Woodward BD, Husain H. New Targets in Non-Small Cell Lung Cancer. Hematol Oncol Clin North Am 2017; 31(1):113−29.

Crinò L, Weder W, van Meerbeeck J, Felip E. ESMO Guidelines Working Group. Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21(Suppl 5):v103−15.

Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346(2): 92−8.

Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011; 61(4): 212−36.

Kawase A, Yoshida J, Ishii G, Nakao M, Aokage K, Hishida T, et al. Differences between squamous cell carcinoma and adenocarcinoma of the lung: are adenocarcinoma and squamous cell carcinoma prognostically equal? Jpn J Clin Oncol 2012; 42(3): 189−95.

Lončarević O, Aćimović S, Vuković J, Stojisavljević M, Marić N, Lončarević S, et al. Overall survival of patients with non-small cell lung cancer after surgery treatment. Vojnosanit Pregl 2018; 75(12): 1157−64.

American Cancer Society. Non-small cell lung cancer stages. Available from: http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-survival-rates[cited 2019 June 13].

Sasaki H, Suzuki A, Tatematsu T, Shitara M, Hikosaki Y, Okuda K, et al. Prognosis of recurrent non-small cell lung cancer following complete resection. Med Lett 2014; 7(4):1300−4.

Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Transl Lung Cancer Res 2014; 3(4): 242−9.

Maeda R, Yoshida J, Ishii G, Hishida T, Nishimura M, Nagai K. Risk factors for tumor recurrence in patients with early-stage (stage I and II) non-small cell lung cancer: patient selection criteria for adjuvant chemotherapy according to the seventh edition TNM classification. Chest 2011; 140(6): 1494−502.

Shoji F, Haro A, Yoshida T, Ito K, Morodomi Y, Yano T, et al. Prognostic significance of intratumoral blood vessel invasion in pathologic stage IA non-small cell lung cancer. Ann Thorac Surg 2010; 89(3): 864−9.

Kerr KM, Bubendorf L, Edelman MJ, Marchetti A, Mok T, Novello S, et al. Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer. Ann Oncol 2014; 25(9): 1681−90.

Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res 2016; 5(3): 288−300.

Zarrabi K, Dufour A, Li J, Kuscu C, Pulkoski-Gross A, Zhi J, et al. Inhibition of matrix metalloproteinase 14 (MMP-14)-mediated cancer cell migration. J Biol Chem 2011; 286(38): 33167−77.

Guo CB, Wang S, Deng C, Zhang DL, Wang FL, Jin XQ. Relationship between matrix metalloproteinase 2 and lung cancer progression. Mol Diagn Ther 2007; 11(3): 183−92.

Merchant N, Nagaraju GP, Rajitha B, Lammata S, Jella KK, Buchwald ZS, et al. Matrix metalloproteinases: their functional role in lung cancer. Carcinogenesis 2017; 38(8): 766−80.

Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010; 141(1): 52−67.

Passlick B, Sienel W, Seen-Hibler R, Wöckel W, Thetter O, Mutschler W, et al. Overexpression of matrix metalloproteinase 2 predicts unfavorable outcome in early-stage non-small cell lung cancer. Clin Cancer Res 2000; 6(10): 3944−8.

Qian Q, Wang Q, Zhan P, Peng L, Wei SZ, Shi Y, et al. The role of matrix metalloproteinase 2 on the survival of patients with non-small cell lung cancer: a systematic review with meta-analysis. Cancer Invest 2010; 28(6): 661−9.

Li XX, Li RJ, Zhao LJ, Liu NB, Wang P. Expression of molecular factors correlated with metastasis in small cell lung cancer and their significance. Int J Clin Exp Pathol 2015; 8(11): 14676−84.

Zhang J, Qi J, Chen N, Fu W, Zhou B, He A. High expression of a disintegrin and metalloproteinase-9 predicts a shortened survival time in completely resected stage I non-small cell lung cancer. Oncol Lett 2013; 5(5):1461−6.

Lee CY, Shim HS, Lee S, Lee JG, Kim DJ, Chung KY. Prognostic effect of matrix metalloproteinase-9 in patients with resected Non small cell lung cancer. J Cardiothorac Surg 2015; 10: 44.

Ricciardi GR, Russo A, Franchina T, Ferraro G, Zanghì M, Picone A, et al. NSCLC and HER2: between lights and shadows. J Thorac Oncol 2014; 9(12): 1750−62.

Mazières J, Peters S, Lepage B, Cortot AB, Barlesi F, Beau-Faller M, et al. Lung cancer that harbors an HER2 mutation: epidemiologic characteristics and therapeutic perspectives. J Clin Oncol 2013; 31(16): 1997−2003.

Zhao XD, He YY, Gao J, Zhao C, Zhang LL, Tian JY, et al. High expression of Bcl-2 protein predicts favorable outcome in non-small cell lung cancer: evidence from a systematic review and meta-analysis. Asian Pac J Cancer Prev. 2014; 15(20):8861−9.

Tomita M, Matsuzaki Y, Edagawa M, Shimizu T, Hara M, Onitsuka T. Prognostic significance of bcl-2 expression in resected pN2 non-small cell lung cancer. Eur J Surg Oncol 2003; 29(8): 654−7.

Mineo TC, Ambrogi V, Baldi A, Rabitti C, Bollero P, Vincenzi B, et al. Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel invasion after radical surgery for IB-IIA non-small cell lung cancer. J Clin Pathol 2004; 57(6): 591−7.

Conde E, Angulo B, Redondo P, Toldos O, García-García E, Suárez-Gauthier A, et al. The use of P63 immunohistochemistry for the identification of squamous cell carcinoma of the lung. PLoS One 2010; 5(8): e12209.

Massion PP, Taflan PM, Jamshedur Rahman SM, Yildiz P, Shyr Y, Edgerton ME, et al. Significance of p63 amplification and overexpression in lung cancer development and prognosis. Cancer Res 2003; 63(21): 7113−21.

Cvetković G, Plavec G, Tatomirović Ž, Jović M, Lončarević O, Trifunović Z, et al. Expression of P63 as predictive and prognostic factor in advanced non-small-cell lung cancer. Vojnosanit Pregl 2018; 75(4): 366−73.

Ko E, Lee BB, Kim Y, Lee EJ, Cho EY, Han J, et al. Association of RASSF1A and p63 with poor recurrence-free survival in node-negative stage I-II non-small cell lung cancer. Clin Cancer Res 2013; 19(5): 1204−12.

Published
2021/12/23
Section
Original Paper