Preview

Russian Journal of Biotherapy

Advanced search

Expression rate of ALK tyrosine kinase and TAG-72 oncoprotein in primary skin melanoma

https://doi.org/10.17650/1726-9784-2018-17-3-50-54

Abstract

Objective.Determine the frequency of occurrence of tyrosine kinase expression of the mutated ALK and TAG-72 gene among patients with primary melanoma of the skin, to identify their association with a number of histological parameters, and to assess the diagnostic value of the determination of ALK and TAG-72.

Materials and methods.Paraffin blocks with surgical material from 40 patients with primary skin melanoma. For routine histological examination, the material was fixed with 10 % neutral formalin for 24 h, poured into paraffin, sections were prepared with a thickness of 4–5 μm, stained with hematoxylin and eosin. IHC study with monoclonal antibodies D57.3 to ALK was performed on an immunostender – Ventana, with antibodies B72.3 to TAG-72 – on Thermo Fischer. As a detection system used: Envision – for TAG-72 and Ventana – for ALK.

Results.ALK mutation was detected in 7 (12 %), TAG-72 – 4 (10 %) cases. Evaluation of the correlation force between the presence of ALK and TAG-72 showed a direct average coupling strength (correlation coefficient was 0.31). A direct correlation of the mean force between the presence of TAG-72 oncoprotein, ALK mutation and ulceration in the patient was found – the correlation coefficient was 0.53 and 0.68, respectively. There was a statistically significant association between the presence of ALK and lymphoid infiltration, which in most cases (57 %) was pronounced (p <0.05).

Conclusion.Comparing the positive sign of the expression of ALK – 17.5 % and TAG-72 – 10 %, and the positive of their simultaneous detection – 7.5 %, it can be concluded that further studies to determine their diagnostic value are promising. The presence of severe lymphoid infiltration in ALK-positive patients claims a diagnostic value in primary skin melanoma.

About the Authors

K. S. Titov
Moscow Clinical Scientific Center, Moscow Health Department
Russian Federation

86 Shosse Entuziastov, Moscow 111123



D. L. Rotin
S.P. Botkin City Clinical Hospital, Moscow Health Department
Russian Federation

7 Mamonovsky Pereulok, Moscow 123001



A. M. Kazakov
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia
Russian Federation

1 Ostrovityanova St., Moscow 117997



O. U. Micheeva
Moscow Clinical Scientific Center, Moscow Health Department
Russian Federation

86 Shosse Entuziastov, Moscow 111123



I. M. Telezhnikova
Moscow Clinical Scientific Center, Moscow Health Department
Russian Federation

86 Shosse Entuziastov, Moscow 111123



D. A. Ryabchikov
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

24 Kashirskoe Shosse, Moscow 115478



References

1. Evans M.S., Madhunapantula S.V., Robertson G.P., Drabick J.J. Current and Future Trials of Targeted Therapies in Cutaneous Melanoma. Adv Exp Med Biol 2013;779:223–55. DOI:10.1007/978-1-4614-6176-0_10. PMID: 23288642.

2. Dhomen N., Marais R. BRAF signaling and targeted therapies in melanoma. Hematol Oncol Clin North Am 2009;23(3):529–45. PMID: 19464601.

3. Jazirehi A.R., Lim A., Dinh T. PD-1 inhibition and treatment of advanced melanoma-role of pembrolizumab. Am J Cancer Res. 2016;6(10):2117–28.PMID: 27822406.

4. Titov K.S., Chikileva I.O., Kiselevskiy M.V., Kazakov A.M. Lymphoid infiltration, as a predictor of successful immunotherapy with melanoma. Malignant Tumors 2017;1:61–6. DOI:10.18027/2224-5057-2017-1-61-66.

5. Yeh I. Recent advances in molecular genetics of melanoma progression: implications for diagnosis and treatment. Department of Dermatology, Universityof California San Francisco, SanFrancisco, CA, USA.2016, Jun 28; 5. (F1000FacultyRev):1529. DOI:10.12688/f1000research.8247.1 PMID: 27408703.

6. Roskoski R.Jr. Anaplastic lymphoma kinase (ALK) inhibitors in the treatment of ALK-driven lung cancers. Pharmacol Res 2017;117:343–56. DOI:10.1016/j.phrs.2017.01.007. PMID: 28077299.

7. Montavon G., Jauquier N., Coulon A. et al. Wild-type ALK and activating ALK-R1275Q and ALK-F1174L mutations upregulate Myc and initiate tumor formation in murine neural crest progenitor cells. Oncotarget 2014;5:4452–66. PMID: 24947326.PMCID: PMC4147337.

8. Takezawa K., Okamoto I., Nishio K. et al. Role of ERK-BIM and STAT3-survivin signaling pathways in ALK inhibitor-induced apoptosis in EML4-ALK-positive lung cancer. Clin Cancer Res 2011;17(8):2140–8. PMID: 21415216.

9. Lemmon M.A., Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2010;141:1117–34. DOI:10.1016/j.cell.2010.06.011. PMID: 20602996.

10. Busam K.J., Villain R.E., Lum T. et al. Primary and metastatic cutaneous melanomas express ALK through alternative transcriptional initiation. Am J Surg Pathol. 2016;40(6):786–95. PMID: 26872010. PMCID: PMC5037961.

11. Sosman J.A., Margolin K.A. Inside life of melanoma cell signaling, molecular insights, and therapeutic targets. Curr Oncol Rep. 2009;11(5):405–11. PMID: 19679016.

12. Obenauf1 A.C., Zou Y., Ji A.L. et al. Therapy-induced tumour secretomes promote resistance and tumour progression. Nature 2015;520(7547): 368–72. DOI: https://doi.org/10.1038/nature14336.

13. Schulte J.H., Bachmann H.S., Brockmeyer B. et al. High ALK receptor tyrosine kinase expression supersedes ALK mutation as a determining facto rof an unfavorable phenotype in primary neuroblastoma. Clin. Cancer Res 2011;17:5082–92. PMID: 21632861.

14. Cheng D.T., Mitchell T.N., Zehir A. et al. Memorial sloan ketter ingintegrated mutation profiling of actionable cancer targets (MSK-IMPACT): a hybridization capture-based nextgeneration sequencing clinical assay for solid tumor molecular oncology. J.Mol. Diagn 2015;17:251–64. PMID: 25801821.

15. Couts K.L., Bemis J., Turner J.A. et al. ALK Inhibitor response in melanomas expressing eml4-alk fusions and alternate ALK isoforms. Mol Cancer Ther. 2018;17(1):222–3. PMID: 29054983.

16. Deo Y.M., Tibor K. Bispecific molecules directed to tumor associated glycoprotein-72 and fc receptor. 1997. Pub. No.:WO/1999/019362 International Application No.: PCT/us 1997/018428.


Review

For citations:


Titov K.S., Rotin D.L., Kazakov A.M., Micheeva O.U., Telezhnikova I.M., Ryabchikov D.A. Expression rate of ALK tyrosine kinase and TAG-72 oncoprotein in primary skin melanoma. Russian Journal of Biotherapy. 2018;17(3):50-54. (In Russ.) https://doi.org/10.17650/1726-9784-2018-17-3-50-54

Views: 487


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1726-9784 (Print)
ISSN 1726-9792 (Online)