Display options
Cite
Alese OB, El-Rayes BF, Sica G, et al. Anaplastic lymphoma kinase (ALK) gene alteration in signet ring cell carcinoma of the gastrointestinal tract. Ther Adv Med Oncol. 2015;7(2):56-62doi: 10.1177/1758834014567117.
Alese, O. B., El-Rayes, B. F., Sica, G., Zhang, G., Alexis, D., La Rosa, F. G., Varella-Garcia, M., Chen, Z., Rossi, M. R., Adsay, N. V., Khuri, F. R., & Owonikoko, T. K. (2015). Anaplastic lymphoma kinase (ALK) gene alteration in signet ring cell carcinoma of the gastrointestinal tract. Therapeutic advances in medical oncology, 7(2), 56-62. https://doi.org/10.1177/1758834014567117
Alese, Olatunji B, et al. "Anaplastic lymphoma kinase (ALK) gene alteration in signet ring cell carcinoma of the gastrointestinal tract." Therapeutic advances in medical oncology vol. 7,2 (2015): 56-62. doi: https://doi.org/10.1177/1758834014567117
Alese OB, El-Rayes BF, Sica G, Zhang G, Alexis D, La Rosa FG, Varella-Garcia M, Chen Z, Rossi MR, Adsay NV, Khuri FR, Owonikoko TK. Anaplastic lymphoma kinase (ALK) gene alteration in signet ring cell carcinoma of the gastrointestinal tract. Ther Adv Med Oncol. 2015 Mar;7(2):56-62. doi: 10.1177/1758834014567117. PMID: 25755678; PMCID: PMC4346214.
Copy Download .nbib Format: NLM
Share it on

Ther Adv Med Oncol. 2015 Mar;7(2):56-62. doi: 10.1177/1758834014567117.

Anaplastic lymphoma kinase (ALK) gene alteration in signet ring cell carcinoma of the gastrointestinal tract.

Therapeutic advances in medical oncology

Olatunji B Alese, Bassel F El-Rayes, Gabriel Sica, Guojing Zhang, Dianne Alexis, Francisco G La Rosa, Marileila Varella-Garcia, Zhengjia Chen, Michael R Rossi, Nazim V Adsay, Fadlo R Khuri, Taofeek K Owonikoko

Affiliations

  1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
  2. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
  3. Cancer Tissue and Pathology Shared Resource (CTPSR), Winship Cancer Center of Emory University, Atlanta, GA, USA.
  4. Department of Pathology, University of Colorado School of Medicine, Denver, CO, USA.
  5. Department of Statistics, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
  6. Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA.
  7. Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365 Clifton Road, NE, Room C3080, Atlanta, GA 30322, USA.

PMID: 25755678 PMCID: PMC4346214 DOI: 10.1177/1758834014567117

Abstract

OBJECTIVES: ALK-EML4 translocation is an established driver aberration in non-small cell lung cancer (NSCLC), with reported predilection for cases with signet ring histology. We assessed the presence of anaplastic lymphoma kinase (ALK) gene rearrangements in signet ring cancers arising in the stomach and colon.

METHODS: Histologically confirmed cases of signet ring adenocarcinoma of the stomach or the colon were identified. The presence of the classic ALK and EML4 fusion gene was initially determined by fluorescence in-situ hybridization (FISH) technique. Immunohistochemistry (IHC) was performed using two previously validated antibodies, ALK1 clone (1:100; DAKO) and 5A4 (Novocastra, Leica Biosystems) along with positive controls of ALK-translocated lung cancer.

RESULTS: We employed 42 cases of signet ring carcinoma diagnosed between 2001 and 2011; 25 gastric and 17 colon cancer. Median age 63.3 years; male/female 17/25; race, black 47.5%, white 47.5%, others, 5%; stage I, 21.4%; stage II, 31%; stage III, 26.2%; stage IV, 21.4%. One of 42 cases (2.3%) was positive for ALK translocation by FISH using the standard criteria of at least 15% positive cells for the break-apart signal (50-70 cells enumerated per case). Using a less restrictive cut-off of 10% positive cells, 7 cases (16%) were considered possibly positive. None of the 'possibly positive' cases was found to harbor ALK translocation by another molecular testing approach (IHC). IHC with two previously validated monoclonal antibodies showed 0 of 42 (0%) cases positive.

CONCLUSIONS: ALK gene rearrangement is very rare in gastrointestinal cancers and enrichment strategy focusing on signet ring cell histology did not significantly improve the detection rate.

Keywords: ALK rearrangement; ALK-EML4 fusion; colon; signet ring cell cancer; stomach

References

  1. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3336-40 - PubMed
  2. Lung Cancer. 2012 Mar;75(3):300-5 - PubMed
  3. J Clin Pathol. 2010 Dec;63(12):1066-70 - PubMed
  4. Clin Cancer Res. 2004 Jun 1;10(11):3885-96 - PubMed
  5. Br J Cancer. 2013 Nov 12;109(10):2735-43 - PubMed
  6. Clin Cancer Res. 2010 Mar 1;16(5):1561-71 - PubMed
  7. Nat Rev Clin Oncol. 2011 Aug 23;8(10):587-96 - PubMed
  8. Cancer. 2012 Sep 15;118(18):4486-94 - PubMed
  9. Gastric Cancer. 2014 Jan;17(1):43-53 - PubMed
  10. Pigment Cell Melanoma Res. 2013 Sep;26(5):646-53 - PubMed
  11. Springerplus. 2013 Aug 28;2:409 - PubMed
  12. Cancer. 2013 Apr 15;119(8):1467-77 - PubMed
  13. Mol Cancer Res. 2009 Sep;7(9):1466-76 - PubMed
  14. Mol Cancer Res. 2014 Jan;12 (1):111-8 - PubMed
  15. J Thorac Oncol. 2011 Mar;6(3):459-65 - PubMed
  16. J Clin Oncol. 2009 Sep 10;27(26):4247-53 - PubMed
  17. J Pathol. 2007 Jul;212(3):278-86 - PubMed
  18. Pharmacol Res. 2013 Feb;68(1):68-94 - PubMed
  19. N Engl J Med. 2010 Oct 28;363(18):1693-703 - PubMed
  20. Int J Cancer. 2010 Dec 15;127(12):2893-917 - PubMed
  21. Trans R Soc Trop Med Hyg. 1988;82(3):412-5 - PubMed
  22. Clin Cancer Res. 2009 Aug 15;15(16):5216-23 - PubMed
  23. Clin Cancer Res. 2009 Sep 15;15(18):5609-14 - PubMed
  24. Expert Opin Ther Targets. 2012 Apr;16 Suppl 2:S45-54 - PubMed
  25. J Clin Oncol. 2012 Oct 1;30(28):3493-8 - PubMed
  26. J Thorac Oncol. 2011 May;6(5):942-6 - PubMed
  27. Breast Cancer Res Treat. 2012 Jul;134(2):561-7 - PubMed
  28. Nature. 2007 Aug 2;448(7153):561-6 - PubMed

Publication Types

Grant support