Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012, 156(2):135-142 | DOI: 10.5507/bp.2012.036

Analysis of the prognostic impact of nestin expression in non-small cell lung cancer

Jozef Skardaa, Zdenek Kolara, Maria Janikovaa, Lenka Radovab, Vitezslav Kolekc, Edi Fridmand, Juri Kopolovice
a Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
b Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University Olomouc
c Department of Tuberculosis and Respiratory Diseases, Faculty of Medicine and Dentistry, Palacky University Olomouc
d Department of Pathology, The Chaim Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
e Department of Pathology, Hadassah Medical School, Hebrew University, Jerusalem, Israel

Background: Nestin is an intermediary filament protein, expressed in progenitor cells of neural and muscle origin and in activated endothelium. The expression of this protein in tumours can be associated with degree of differentiation, biological potential and/or neoangiogenesis.

Aims: The aim of this study was to examine the immunohistochemical expression of nestin in primary non-small cell lung carcinomas (NSCLC) and to determine its prognostic significance.

Methods: Immunohistochemical detection of nestin was carried out on tissue microarrays constructed from 114 formalin-fixed and paraffin-embedded NSCLC samples. These included 78 squamous cell carcinomas and 37 adenocarcinomas. Expression of nestin was also analysed in 35 primary tumour independent NSCLC brain metastasis. The H-score and degree of nestin positive microvascularisation were determined. Both parameters correlated with the clinicopathological characteristics including disease-free and overall survival.

Results: We demonstrated that expression of nestin is not significantly higher in tumour cells of adenocarcinomas than in sqamous cell carcinomas despite the fact that adenocarcinomas were more frequently positive (P≤0.30). On the other hand, nestin positivity and nestin positive neovascularisation were significantly more often found in stage IIIa tumours than tumours in stages I and II (P≤0.04, P≤0.02). Nestin expression was also significantly higher in brain metastases of squamous cell carcinomas than brain metastases of adenocarcinomas (P≤0.003). The expression of nestin, in general, did not significantly correspond to disease-free or overall survival.

Conclusion: Nestin expression in NSCLCs is associated with poorer prognosis and with greater nestin-positive microvessel density.

Keywords: nestin, non-small cell lung cancer, brain metastasis, immunohistochemistry, prognosis

Received: August 2, 2011; Accepted: February 29, 2012; Published: June 1, 2012  Show citation

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Skarda, J., Kolar, Z., Janikova, M., Radova, L., Kolek, V., Fridman, E., & Kopolovic, J. (2012). Analysis of the prognostic impact of nestin expression in non-small cell lung cancer. Biomedical papers, 156(2), 135-142. doi: 10.5507/bp.2012.036
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    References

    1. Lendahl U, Zimmerman LB, McKay RD. CNS stem cells express a new class of intermediate filament protein. Cell 1990;60:585-95. Go to original source... Go to PubMed...
    2. Marvin MJ, Dahlstrand J, Lendahl U, McKay RD. A rod end deletion in the intermediate filament protein nestin alters its subcellular localization in neuroepithelial cell sof transgenic mice. J Cell Sci 1998;111:1951-61. Go to original source... Go to PubMed...
    3. Sugawara K, Kurihara H, Negishi M, Saito N, Nakazato Y, Sasaki T, Takeuchi T. Nestin as a marker for proliferative endothelium in gliomas. Lab Invest 2002;82:345-51. Go to original source... Go to PubMed...
    4. Mokry J, Cizkova D, Filip S, Ehrmann J, Osterreicher J, Kolár Z, English D. Nestin expression by newly formed human blood vessels. Stem Cells Dev 2004;13:658-64. Go to original source... Go to PubMed...
    5. Almazan G, Vela JM, Molina-Holgado E, Guaza C. Reevaluation of nestin as a marker of oligodendrocyte lineage cells. Microsc Res Tech 2001;52:753-65. Go to original source... Go to PubMed...
    6. Krum JM, Rosenstein JM. Transient coexpression of nestin,GFAP, and vascular endothelial growth factor in mature reactive astroglia following neural grafting or brain wounds. Exp Neurol 1999;160:348- 60. Go to original source... Go to PubMed...
    7. Frojdman K, Pelliniemi LJ, Lendahl U, Virtanen I and Eriksson JE. The intermediate filament protein nestin occurs transiently in differentiating testis of rat and mouse. Differentiation 1997;61:243-9. Go to original source... Go to PubMed...
    8. Amoh Y, Li L, Yang M, Moossa AR, Katsuoka K, Penman S, Hoffman RM. Nascent blood vessels in the skin arise from nestin-expressing hair-follicle cells. Proc Natl Acad Sci USA 2004;101:13291-5. Go to original source... Go to PubMed...
    9. Lardon J, Rooman I, Bouwens L. Nestin expression in pancreatic stellate cells and angiogenic endothelial cells. Histochem Cell Biol 2002;117:535-40. Go to original source... Go to PubMed...
    10. Klein T, Ling Z, Heimberg H, Madsen OD, Heller RS, Serup P. Nestin is expressed in vascular endothelial cells in the adult human pancreas. J Histochem Cytochem 2003;51:697-706. Go to original source... Go to PubMed...
    11. Terling C, Rass A, Mitsiadis TA, Fried K, Lendahl U, Wroblewski J. Expression of the intermediate filament nestin during rodent tooth development. Int J Dev Biol 1995;39:947-56.
    12. Kolar Z, Ehrmann J. Jr, Turashvili G., Bouchal J., Mokrý J. A novel myoepitelial/ progenitor cell marker in the breast? Wirchovs Arch 2007;450:607-9. Go to original source... Go to PubMed...
    13. Sejersen T, Lendahl U. Transient expression of the intermediate filament nestin during skeletal muscle development. J Cell Sci 1993;106:1291-1300. Go to original source... Go to PubMed...
    14. El-Helou V, Dupuis J, Proulx C, Drapeau J, Clement R, Gosselin H, Villeneuve L, Manganas L, Calderone A. Resident nestin+ neural-like cells and fibers are detected in normal and damaged rat myocardium. Hypertension 2005;46:1219-1300. Go to original source... Go to PubMed...
    15. Ehrmann J, Kolar Z, Mokry J. Nestin as a diagnostic and prognostic marker: immunohistochemical analysis of its expression in different tumours. J Clin Pathol 2005;58:222-3. Go to original source... Go to PubMed...
    16. Hansen S, Grabau DA, Rose C, Bak M, Sorensen FB. Angiogenesis in breast cancer: a comparative study of the observer variability of methods for determining microvessel density. Lab Invest 1998;78:1563-73.
    17. Schoell WM, Pieber D, Reich O, Lahousen M, Janicek M, Guecer F, Winter R. Tumor angiogenesis as a prognostic factor in ovarian carcinoma: quantification of endothelial immunoreactivity by image analysis. Cancer 1997;80:2257-62. Go to original source... Go to PubMed...
    18. Vermeulen PB, Gasparini G, Fox SB. Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria of evaluation. Eur J Cancer 1996;32A:2474-84. Go to original source... Go to PubMed...
    19. Tomisaki S, Ohno S, Ichiyoshi Y, Kuwano H, Maehara Y, Sugimachi K. Microvessel quantification and its possible relation with liver metastasis in colorectal cancer. Cancer 1996;77:1722-8. Go to original source... Go to PubMed...
    20. Liotta LA, Saidel MG, Kleinerman J. The significance of hematogenous tumor cell clumps in the metastatic process. Cancer Res 1976;36:889-94.
    21. Wakui S, Furusato M, Itoh T, Sasaki H, Akiyama A, Kinoshita I, Asano K, Tokuda T, Aizawa S, Ushigome S. Tumour angiogenesis in prostatic carcinoma with and without bone marrow metastasis: a morphometric study. J Pathol 1992;168:257-62. Go to original source... Go to PubMed...
    22. Tanigawa N, Matsumura M, Amaya H, Kitaoka A, Shimomatsuya T, Lu C, Muraoka R, Tanaka T. Tumor vascularity correlates with the prognosis of patients with esophageal squamous cell carcinoma. Cancer 1997;79:220-25. Go to original source... Go to PubMed...
    23. Tanigawa N, Amaya H, Matsumura M, Shimomatsuya T. Association of tumour vasculature with tumour progression and overall survival of patients with non-early gastric carcinomas. Br J Cancer 1997;75:566-71. Go to original source... Go to PubMed...
    24. Kim HS, Kang HS, Messam CA, Min KW, Park CS. Comparative evaluation of angiogenesis in gastric adenocarcinoma by nestin and CD34. Appl Immunohistochem Mol Morphol 2002;10:121-7. Go to original source... Go to PubMed...
    25. Tomoda M, Maehara Y, Kakeji Y, Ohno S, Ichiyoshi Y, Sugimachi K. Intratumoral neovascularization and growth pattern in early gastric carcinoma. Cancer 1999;85:2340-6. Go to original source... Go to PubMed...
    26. Takahashi Y, Tucker SL, Kitadai Y, Koura AN, Bucana CD, Cleary KR, Ellis LM. Vessel counts and expression of vascular endothelial growth factor as prognostic factors in node-negative colon cancer. Arch Surg 1997;132:541-6. Go to original source... Go to PubMed...
    27. Uzzan B, Nicolas P, Cucherat M, Perret GY. Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis. Cancer Res 2004;64:2941-55. Go to original source... Go to PubMed...
    28. Vieira SC, Zeferino LC, Da Silva BB, Aparecida Pinto G, Vassallo J, Carasan GA, De Moraes NG. Quantification of¨angiogenesis in cervical cancer: a comparison among three endothelial cell markers. Gynecol Oncol 2004;93:121-4. Go to original source... Go to PubMed...
    29. Srivastava A, Laidler P, Hughes LE, Woodcock J, Shedden EJ. Neovascularization in human cutaneous melanoma: a quantitative morphological and Doppler ultrasound study. Eur J Cancer Clin Oncol 1986;22:1205-9. Go to original source... Go to PubMed...
    30. Macchiarini P, Fontanini G, Hardin MJ, Squartini F, Angeletti CA. Relation of neovascularisation to metastasis of non-small-cell lung cancer. Lancet 1992;340:145-6. Go to original source... Go to PubMed...
    31. Meert AP, Paesmans M, Martin B, Delmotte P, Berghmans T, Verdebout JM, Lafitte JJ, Mascaux C, Sculier JP. The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer 2002;87:694- 701. Go to original source... Go to PubMed...
    32. Yano T, Tanikawa S, Fujie T, Masutani M, Horie T. Vascular endothelial growth factor expression and neovascularisation in non-small cell lung cancer. Eur J Cancer 2000;36:601-9. Go to original source... Go to PubMed...
    33. Offersen BV, Pfeiffer P, Hamilton-Dutoit S, Overgaard J. Patterns of angiogenesis in nonsmall-cell lung carcinoma. Cancer 2001;91:1500- 9. Go to original source... Go to PubMed...
    34. Chen Z, Wang T, Luo H, Lai Y, Yang X, Li F, Lei Y, Su C, Zhang X, Lahn B T, Xiang A P. Expression of nestin regarding to lymf node metastasis and lymphangiogenesis in non-small cell lung cancer patiens. Human Pathol 2010;41:737-44. Go to original source... Go to PubMed...
    35. Bieberich E, MacKinnon S, Silva J, Noggle S, Condie BG. Regulation of cell death in mitotic neural progenitor cells by asymmetric distribution of prostate apoptosis response 4 (PAR-4) and simultaneous elevation of endogenous ceramide. J Cell Biol 2003;162:469-79. Go to original source... Go to PubMed...
    36. Sahlgren CM, Mikhailov A, Vaittinen S, Pallari HM, Kalimo H, Pant HC, Eriksson JE. Cdk5 regulates the organization of nestin and its association with p35. Mol Cell Biol 2003;23:5090-106. Go to original source... Go to PubMed...
    37. Ryuge S, Sato Y, Wang GQ, Matsumoto T, Jiang SX, Katono K, Inoue H, Satoh Y, Masuda N. Prognostic significance of nestin expression in resected non-small cell lung cancer. Chest 2010;139:862-9. Go to original source... Go to PubMed...
    38. Li H, Cherukuri P, Li N, Cowling V, Spinella M, Cole M, Godwin AK, Wells W, DiRenzo J. Nestin is expressed in the basal/myoepithelial layer of the mammary gland and is a selective marker of basal epithelial breast tumors. Cancer Res 2007;67:501-10. Go to original source... Go to PubMed...
    39. Parry S, Savage K, Marchió C, Reis-Filho J S. Nestin is expressed in basal-like and triple negative breast cancers. J Clin Pathol 2008;61:1045-50. Go to original source... Go to PubMed...
    40. Mokrý J, Nemecek S. Angiogenesis of extra- and intraembryonic blood vessels is associated with expression of nestin in endothelial cells. Folia Biol (Praha) 1998;44:155-61. Go to PubMed...

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