Advances in Clinical and Experimental Medicine

Adv Clin Exp Med
Impact Factor (IF) – 1.514
Index Copernicus (ICV 2018) – 157.72
MNiSW – 40
Average rejection rate – 84.38%
ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download PDF

Advances in Clinical and Experimental Medicine

2015, vol. 24, nr 4, July-August, p. 715–723

doi: 10.17219/acem/28825

Publication type: review article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Creative Commons BY-NC-ND 3.0 Open Access

Detection of Chromosomal Abnormalities with Different In Situ Hybridisation Techniques – the Usefulness in the Qualification of Cancer Patients for Molecularly-Targeted Therapies

Marcin Nicoś1,A,B,C,D,F, Kamila Wojas-Krawczyk2,A,C,E,F, Paweł Krawczyk2,A,E,F, Janusz Milanowski2,A,E,F

1 Department of Pneumonology, Oncology and Allergology, Medical University of Lublin Postgraduate School of Molecular Medicine, Medical University of Warsaw, Poland

2 Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Poland

Abstract

Proper qualification of patients with cancer for an effective treatment regiment is essential to rationalize therapy benefit and costs. The early detection of genetic disorders that are responsible for the stimulation of uncontrolled cancer cells proliferation makes it possible to select a group of patients with a high probability of response to molecularly-targeted therapy. Data has shown that careful analysis of genes mutation using different PCR and sequencing techniques or chromosomal aberrations using in situ hybridization (ISH) techniques have a predictive value for drug targeted therapy. Overexpression of receptors and gene amplification has been reported in various cancers. Their detection is still a considerable challenge, which is connected with the unsatisfactory quality of DNA and low mutated cells percentage compared to cells with no genetic abnormalities in tested material. Different techniques of standardization were performed to prevent false negative results and to increase the sensitivity of qualitative and quantitative evaluation of chromosomal abnormalities. Immunohistochemistry (IHC) technique is useful in the screening of receptor expression in paraffin-embedded tissue samples in different malignant diseases. Whereas ISH techniques, especially fluorescence in situ hybridization (FISH), are now considered the diagnostic gold standard method in detection chromosomal aberrations. Moreover, molecular biology techniques, which are using molecular probes and real-time PCR and quantitative PCR techniques, were also applied for the detection of chromosomal changes. In order to identify the best genetic marker for treatment regiment, it is important to compare results of different studies, which are evaluating the sensitivity of diagnostic techniques and treatment response after a suitable selection factors based on genetic aberrations profile.

Key words

immunohistochemistry, genetic driver abnormalities, in situ hybridization, molecularly-targeted therapies.

References (45)

  1. Jemal A, Bray F, Center MM, Ferlay J: Global cancer statistics. CA Cancer J Clin 2011, 61, 69–90.
  2. Planchard D: Identification of driver mutations in lung cancer: first step in personalized cancer. Targ Oncol 2013, 8, 3–14.
  3. Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, Squire J, Lorimer I, Zhang T, Liu N, Daneshmand M, Marrano P, da Cunha Santos G, Lagarde A, Richardson F, Seymour L, Whitehead M, Ding K, Pater J, Shepherd FA: Erlotinib in lung cancer – molecular and clinical predictors of outcome. N Engl J Med 2005, 353,133–144.
  4. Gnad F, Baucom A, Mukhyala K, Manning G, Zhang Z: Assessment of computational methods for predicting the effects of missense mutations in human cancers. BMC Genomics 2013. DOI:10.1186/1471-2164-14-S3-S7.
  5. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW: Cancer genome landscapes. Science 2013, 29, 1546–1558.
  6. Sartore-Bianchi A, Fieuws S, Veronese S, Moroni M, Personeni N, Frattini M, Torri V, Cappuzzo F, Borght SV, Martin V, Skokan M, Santoro A, Gambacorta M, Tejpar S, Varella-Garcia M, Siena S: Standardisation of EGFR FISH in colorectal cancer: results of an international interlaboratory reproducibility ring study. J Clin Pathol 2012, 65, 218–223.
  7. Jiang Z, Li C, Li F, Wang X: EGFR gene copy number as a prognostic marker in colorectal cancer patients treated with cetuximab or panitumumab: A systematic review and meta analysis. PLoS ONE 2013, 8, 56205–56212.
  8. Sauter G, Lee J, Bartlett J, Slamon DJ, Press MF: Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodological considerations. J Clin Oncol 2009, 27, 1323–1333.
  9. Han CB, Ma JT, Li F, Zou HW: Molecular markers for the prediction of anti-EGFR monoclonal antibody treatment efficacy in metastatic colorectal cancer. J Cancer Therapy 2011, 2, 675–682.
  10. Cortes J, Fumoleau P, Bianchi GV, Petrella TM, Gelmon K, Pivot X, Verma S, Albanell J, Conte P, Lluch A, Salvagni S, Servent V, Gianni L, Scaltriti M, Ross GA, Dixon J, Szado T, Baselga J: Pertuzumab monotherapy after trastuzumab-based treatment and subsequent reintroduction of trastuzumab: activity and tolerability in patients with advanced human epidermal growth factor receptor 2–positive breast cancer. J Clin Oncol 2012, 30, 1594–1600.
  11. Thunnissen E, Bubendorf L, Dietel M, Elmberger G, Kerr K, Lopez-Rios F, Moch H, Olszewski W, Pauwels P, Penault-Llorca F, Rossi G: EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations. Virchows Arch 2012, 461, 245–257.
  12. Marchetti A, Ardizzoni A, Papotti M, Crinò L, Rossi G, Gridelli C, Barberis M, Maiorano E, Normanno N, Taddei GL, Scagliotti G, Clemente C, Pinto C: Recommendations for the analysis of ALK gene rearrangements in non-small-cell lung cancer. A consensus of the Italian Association of Medical Oncology and the Italian Society of Pathology and Cytopathology. J Thorac Oncol 2013, 8, 352–358.
  13. Sholl LM, Xiao Y, Joshi V, Yeap BY, Cioffredi LA, Jackman DM, Lee C, Jänne PA, Lindeman NI: EGFR mutation is a better predictor of response to tyrosine kinase inhibitors in non–small cell lung carcinoma than FISH, CISH, and immunohistochemistry. Am J Clin Pathol 2010, 133, 922–934.
  14. Furrer D, Jacob S, Caron C, Sanschagrin F, Provencher L, Diorio C: Validation of a new classifier for the automated analysis of the human epidermal growth factor receptor 2 (HER2) gene amplification in breast cancer specimens. Diagn Pathol 2013, 8, 17–26.
  15. Murakami Y, Mitsudomi T, Yatabe YA: A screening method for the ALK fusion gene in NSCLC. Front Oncol 2012. DOI: 10.3389/fonc.2012.00024.
  16. Untch M, Lück HJ: Lapatinib – member of a new generation of ErbB-targeting drugs. Breast Care 2010, 5, 8–12.
  17. Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY: Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet 2008, 372, 1809–1818.
  18. Wang F, Fu S, Shao Q, Zhou YB, Zhang X, Zhang X, Xue C, Lin JG, Huang LX, Zhang L, Zhang WM, Shao JY: High EGFR copy number predicts benefits from tyrosine kinase inhibitor treatment for non-small cell lung cancer patients with wild-type EGFR. J Transl Med 2013, 11, 90–100.
  19. Liang Z, Zhang J, Zeng X, Gao J, Wu S, Liui T: Relationship between EGFR expression, copy number and mutation in lung adenocarcinomas. BMC Cancer 2010, 10, 376–385.
  20. Brugger W, Triller N, Blasinska-Morawiec M, Curescu S, Sakalauskas R, Manikhas GM, Mazieres J, Whittom R, Ward C, Mayne K, Trunzer K, Cappuzzo F: Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non–small-cell lung cancer. J Clin Oncol 2011, 29, 4113–4120.
  21. Fukuoka M, Wu YL, Thongprasert S, Sunpaweravong P, Leong SS, Sriuranpong V, Chao TY, Nakagawa K, Chu DT, Saijo N, Duffield EL, Rukazenkov Y, Speake G, Jiang H, Armour AA, To KF, Yang YC, Mok TDK: Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non–small-cell lung cancer in Asia (IPASS). J Clin Oncol 2011, 29, 2866–2874.
  22. Yi ES, Boland JM, Maleszewski JJ, Roden AC, Oliveira AM, Aubry MC, Erickson-Johnson MR, Caron BL, Li Y, Tang H, Stoddard S, Wampfler J, Kulig K, Yang P: Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma. IHC score algorithm for FISH. J Thorac Oncol 2011, 6, 459–465.
  23. Kim H, Yoo SB, Choe JY, Paik JH, Xu X, Nitta H, Zhang W, Grogan TM, Lee CT, Jheon S, Chung JH: Detection of ALK gene rearrangement in non-small cell lung cancer: A comparison of fluorescence in situ hybridization and chromogenic in situ hybridization with correlation of ALK protein expression. J Thorac Oncol 2011, 6, 1359–1366.
  24. Chen TD, Chang IC, Liu HP, Wu YC, Wang CL, Chen YT, Chen YR, Huang SF: Correlation of anaplastic lymphoma kinase overexpression and the EML4-ALK fusion gene in non-small cell lung cancer by immunohistochemical study. Chang Gung Med J 2012, 34, 309–317.
  25. Zhang YG, Jin ML, Li L, Zhao HY, Zeng X, Jiang L, Wei P, Diao XL, Li X, Cao Q, Tian XX: Evaluation of ALK rearrangement in Chinese non-small cell lung cancer using FISH, immunohistochemistry, and real-time quantitative RT-PCR on paraffin-embedded tissues. PLoS One 2013. DOI:10.1371/journal.pone.0064821.
  26. Wu YC, Chang IC, Wang CL, Chen TD, Chen YT, Liu HP, Chu Y, Chiu YT, Wu TH, Chou LH, Chen YR, Huang SF: Comparison of IHC, FISH and RT-PCR methods for detection of ALK rearrangements in 312 nonsmall cell lung cancer patients in Taiwan. PLoS ONE 2013 8: e70839. DOI:10.1371/journal.pone.0070839.
  27. Bergethon K, Shaw AT, Ou SH, Katayama R, Lovly CM, McDonald NT, Massion PP, Siwak-Tapp C, Gonzalez A, Fang R, Mark EJ, Batten JM, Chen H, Wilner KD, Kwak EL, Clark JW, Carbone DP, Ji H, Engelman JA, Mino-Kenudson M, Pao W, Iafrate AJ: ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol 2012, 30, 863–870.
  28. Davies KD, Le AT, Theodoro MF, Skokan MC, Aisner DL, Berge EM, Terracciano LM, Cappuzzo F, Incarbone M, Roncalli M, Alloisio M, Santoro A, Camidge DR, Varella-Garcia M, Doebele RC: Identifying and targeting ROS1 gene fusions in non-small cell lung cancer. Clin Cancer Res 2012, 18, 4570–4579.
  29. Jacquemier J, Spyratos F, Esterni B, Mozziconacci MJ, Antoine M, Arnould L, Lizard S, Bertheau P, Lehmann-Che J, Fournier CB, Krieger S, Bibeau F, Lamy PJ, Chenard MP, Legrain M, Guinebretière JM, Loussouarn D, Macgrogan G, Hostein I, Mathieu MC, Lacroix L, Valent A, Robin YM, Revillion F, Triki ML, Seaume A, Salomon AV, de Cremoux P, Portefaix G, Xerri L, Vacher S, Bièche I, Penault-Llorca F: SISH/CISH or qPCR as alternative techniques to FISH for determination of HER2 amplification status on b
  30. Gullo G, Bettio D, Zuradelli M, Masci G, Giordano L, Bareggi C, Tomirotti M, Salvini P, Runza L, La Verde N, Santoro A: Level of HER2/neu amplification in primary tumours and metastases in HER2-positive breast cancer and survival after trastuzumab therapy. The Breast 2013, 22, 190–193.
  31. Drukker CA, Bueno-de-Mesquita JM, Retèl VP, van Harten WH, van Tinteren H, Wesseling J, Roumen RM, Knauer M, van ‘t Veer LJ, Sonke GS, Rutgers EJ, van de Vijver MJ, Linn SC: A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study. Int J Cancer 2013, 133, 929–936.
  32. Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM: Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012, 366, 109–119.
  33. Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K: Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012, 367, 1783–1791.
  34. Nahta R: New developments in the treatment of HER2-positive breast cancer. Breast Cancer 2012, 4, 53–64.
  35. Hamberg P, Bos MM, Braun HJ, Stouthard JM, van Deijk GA, Erdkamp FL, van der Stelt-Frissen IN, Bontenbal M, Creemers GJ, Portielje JE, Pruijt JF, Loosveld OJ, Smit WM, Muller EW, Schmitz PI, Seynaeve C, Klijn JG: Randomized phase II study comparing efficacy and safety of combination-therapy trastuzumab and docetaxel vs. sequential therapy of trastuzumab followed by docetaxel alone at progression as first-line chemotherapy in patients with HER2+ metastatic breast cancer: HERTAX trial. Clin Breast
  36. Grin A, Brezden-Masley C, Bauer S, Streutker CJ: HER2 in situ hybridization in gastric and gastroesophageal adenocarcinoma: Comparison of automated dual ISH to FISH. Appl Immunohistochem Mol Morphol 2013, 21, 561–566.
  37. Luis M, Tavares A, Carvalho LS, Lara-Santos L, Araújo A, de Mello RA: Personalizing therapies for gastric cancer: Molecular mechanisms and novel targeted therapies. World J Gastroenterol 2013, 38, 6383–6397.
  38. Mello RA, Marques AM, Araújo A: HER2 therapies and gastric cancer: A step forward. World J Gastroenterol 2013, 37, 6165–6169.
  39. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010, 376, 687–697.
  40. Hofmann M, Stoss O, Shi D, Büttner R, van de Vijver M, Kim W, Ochiai A, Rüschoff J, Henkel T: Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008, 52, 797–805.
  41. Lee J, Lee SE, Kang SJ, Do IG, Lee S, Ha SY, Cho J, Kang WK, Jang J, Ou SH, Kim KM: Identification of ROS1 rearrangement in gastric adenocarcinoma. Cancer 2013, 119, 1627–1635.
  42. Lin JK, Lin AJ, Lin CC, Lan YT, Yang SH, Li AF, Chang SC: The status of EGFR-associated genes could predict the outcome and tumor response of chemo-refractory metastatic colorectal patients using cetuximab and chemotherapy. J Sur Oncol 2011, 104, 661–666.
  43. Campanella C, Mottolese M, Cianciulli A, Torsello A, Merola R, Sperduti I, Melucci E, Conti S, Diodoro MG, Zeuli M, Paoletti G, Cognetti F, Garufi C: Epidermal growth factor receptor gene copy number in 101 advanced colorectal cancer patients treated with chemotherapy plus cetuximab. J Transl Med 2010, 8, 36–44.
  44. Algars A, Lintunen M, Carpen O, Ristamäki R, Sundström J: EGFR gene copy number assessment from areas with highest EGFR expression predicts response to anti-EGFR therapy in colorectal cancer. Br J Cancer 2011, 105, 255–262.
  45. Yang AY, Shen WX, Hu XF, Zheng DY, Wu XY, Huang YF, Chen JZ, Mao C, Tang JL: EGFR gene copy number as a predictive biomarker for the treatment of metastatic colorectal cancer with anti-EGFR monoclonal antibodies: a meta-analysis. J Hematol Oncol 2012, 5, 52–61.