Overexpression of p63 Protein in Patients with Seborrheic Keratosis in the Setting of Carbohydrate Metabolism Disorders
https://doi.org/10.25207/1608-6228-2019-26-4-18-25
Abstract
Aim. The paper studies p63 expression in patients with seborrheic keratosis in the presence or absence of carbohydrate metabolism disorders.
Materials and methods. The study involved 130 patients with seborrheic keratosis. Following the endocrinologist’s consultation, the patients were divided into two groups. The fi rst group comprised 68 people: 44 patients with type 2 diabetes and 24 patients with impaired glucose tolerance. The second group was composed of patients without carbohydrate metabolism disorders (62 people). The authors performed a histological study and an immunohistochemical (IHC) test using monoclonal antibodies to р63. The results of the IHC test were analysed according to the number of stained tumour cells: 0 — no response or weak staining of less than 10% of the cells, 1 — from 10% to 30% of tumour cells are stained, 2 — staining of more than 30% of tumor cells; as well as according to the colour intensity: weak (+) and marked (++).
Results. The IHC test using monoclonal antibodies to р63 produced a positive reaction in 82.3% of cases. Sixty-fi ve seborrheic keratomas (SK) (50%) exhibited a diffuse pronounced expression of p63. Weak nuclear staining (10%–30% of cells) was recorded in 42 SKs (32.3%). The study revealed a high correlation dependence of p63 expression in SK on the presence of carbohydrate metabolism disorders in patients (R = 0.82, p = 0.0000001). Thus, in patients with carbohydrate metabolism disorders, overexpression of p63 in SKs was found to be signifi cantly higher — 89.7%, as compared to 6.4% in patients without impaired carbohydrate metabolism (p = 0.00001).
Conclusion. P63 overexpression in seborrheic keratosis correlates with the presence of chronic hyperglycemia in patients. Disruption of cellular metabolism leads to changes in the balance between p63 isoforms and plays an important role in the pathogenesis of seborrheic keratosis.
About the Authors
A. К. Alexandrova
I.M. Sechenov First Moscow State Medical University, Ministry of Healthcare of the Russian Federation (Sechenov University)
Russian Federation
Russian Federation
Alexandra K. Alexandrova — Cand. Sci. (Med.), a doctoral candidate at the Department for Pathological Anatomy named after A.M. Strukov
Trubetskaya str., 8–2, Moscow, 119991
V. A. Smolyannikova
I.M. Sechenov First Moscow State Medical University, Ministry of Healthcare of the Russian Federation (Sechenov University)
Russian Federation
Russian Federation
Vera A. Smolyannikova — Dr. Sci. (Med.), Ass. Prof., Department for Pathological Anatomy named after A.M. Strukov
Trubetskaya str., 8–2, Moscow, 119991
References
1. Gonfl oni S., Caputo V., Iannizzotto V. P63 in health and cancer. Int. J. Dev. Biol. 2015; 59(1–3): 87–93. DOI: 10.1387/ijdb.150045sg
2. Daks A.A., Petukhov A.V., Shuvalov A.Yu., Vasil’eva E.A., Melino D., Barlev N.A., Fedorova O.A. Tumor suppressor p63 regulates expression of ubiquitin ligase Pirh2. Tsitologiya. 2015; 57(12): 876–879 (In Russ., English abstract).
3. Wei J., Zaika E., Zaika A. p53 family: role of protein isoforms in human cancer. J. Nucl. Acids. 2012: 687359. DOI: 10.1155/2012/687359
4. Wang N., Guo L., Rueda B.R., Tilly J.L. Cables1 protects p63 from proteasomal degradation to ensure deletion of cells after genotoxic stress. EMBO Rep. 2010; 11(8): 633–639. DOI: 10.1038/embor.2010.82
5. Pignon J.C., Grizanzio C., Geng Y., Song J., Shivdasani R.A., Signoretti S. p63-expressing cells are the stem cells of developing prostate, bladder, and colorectal epithelia. Proc. Natl. Acad. Sci. USA. 2013; 110(20): 8105–8110. DOI: 10.1073/pnas.1221216110
6. Candi E., Agostini M., Melino G., Bernassola F. How the TP53 family proteins TP63 and TP73 contribute to tumorgenesis:regulators and effectors. Hum. Mutat. 2014; 35(6): 702–714. DOI: 10.1002/humu.22523
7. Napoli M., Flores E.R. The family that eats together stays together:new p53 family transcriptional targets in autophagy. Genes. Dev. 2013; 27(9): 971–974. DOI: 10.1101/gad.219147.113
8. Su X., Gi Y.J., Charkravarti D., Chan I.L., Zhang A., Xia X., Tsai K.Y. Flores E.R. Tap63 is a master transcriptional regulator of lipid and glucose metabolism. Cell Metab. 2012; 16(4): 511–525. DOI: 10.1016/j.cmet.2012.09.006
9. Sakiz D., Turkmenoglu T.T., Kabukcuoglu F. The expression of p63 and p53 in keratoacanthoma and intraepidermal and invasive neoplasms of the skin. Pathol. Res. Pract. 2009; 205(9): 589–594. DOI: 10.1016/j.prp.2009.01.010
10. Park S., Lee S., Kim J., Kim G., Park K.H., Kim T.U., Chung D., Lee H. ΔNp63 to TAp63 expression ratio as a potential molecular marker for cervical cancer prognosis. PLoS One. 2019; 14(4): e0214867. DOI: 10.1371/journal.pone.0214867
11. Re M., Magliulo G., Ferrante L., Zizzi A., Santarelli A., Stramazzotti D., Muzio L.L, Goteri G., Rubini C. p63 expression in laryngeal squamous cell carcinoma is related to tumor extension, histologic grade, lymph node involvement and clinical stage. J. Biol. Regul. Homeost. Agents. 2013; 27(1): 121–129.
12. Chen H., Takahara M., Xie L., Takeuchi S., Tu Y., Nakahara T., Uchi H., Moroi Y., Furue M. Levels of the EMT-related protein Snail/Slug are not correlated with p53/p63 in cutaneous squamous cell carcinoma. J. Cutan. Pathol. 2013; 40(7): 651–656. DOI: 10.1111/cup.12142
13. Seo E.Y., Lee D.H., Lee Y., Cho K.H., Eun H.C., Chung J.H. Microarray analysis reveals increased expression of ΔNp63α in seborrhoeic keratosis. Br. J. Dermatol. 2012; 166(2): 337–342. DOI: 10.1111/j.13652133.2011.10665.x
14. Roh N.K., Hahn H.J., Lee Y.W., Choe Y.B., Ahn K.J. Clinical and histopathologocal investigation of seborrheic keratosis. Ann. Dermatol. 2016; 28(2): 152–158. DOI: 10.5021/ad.2016.28.2.152
15. Molochkov V.A., Molochkov A.V., Khlebnikova A.N., Kuntsevich Zh.S. Epitelial’nye opukholi kozhi [Epithelial tumors of the skin]. Moscow: BINOM; 2012: 224 (In Russ.).
16. Saraiya A., Al-Shoha A., Brodell R.T. Hyperinsulinemia associated with acanthosisnigricans, fi nger pebbles, acrochordons, and the sign of Leser-Trélat. Endocr. Pract. 2013; 19(3): 522–525. DOI: 10.4158/EP12192.RA
17. Aleksandrova A.K., Smol’yannikova V.A. Features of seborrheickeratoses in patients with carbohydrate metabolism disorders.Vestnik Dermatologii i Venerologii. 2018; 94(5): 33–38 (In Russ., English abstract). DOI: 10.25208/0042-4609-2018-94-5-33-38
18. Seo E.Y., Lee D.H., Lee Y., Cho K.H., Eun H.C., Chung J.H. Microarray analysis reveals increased expression of ΔNp63α in seborrhoeic keratosis. Br. J. Dermatol. 2012; 166(2): 337–342. DOI: 10.1111/j.13652133.2011.10665.x
19. Cimpean I., Theate I., Vanhooteghem O. Seborrheic keratosis evolution into squamous cell carcinoma: A truly modifi ed sun-related tumor? A case report and review of the literature. Dermatol. Reports. 2019; 11(1): 7999. DOI: 10.4081/dr.2019.7999
20. Kurihara Y., Furue M. Occult basal cell carcinoma arising in seborrheic keratosis. Case Rep. Dermatol. 2019; 11(1): 48–51. DOI: 10.1159/000497067
21. Hillen L.M., Rennspiess D., Speel E.J., Haugg A.M. Winnepenninckx V., ZurHausen A. Detection of merkel cell polyomavirus in seborrheic keratosis. Front. Microbiol. 2017; 8: 2648. DOI: 10.3389/fmicb.2017.02648
22. Klyushin D.A., Petunin Yu.I. Dokazatel’naya meditsina: Primenenie statisticheskikh metodov [Evidence based medicine: using statistical methods]. Moscow: Dialektika; 2017: 316 (In Russ.).
Review
For citations:
Alexandrova A.К., Smolyannikova V.A. Overexpression of p63 Protein in Patients with Seborrheic Keratosis in the Setting of Carbohydrate Metabolism Disorders. Kuban Scientific Medical Bulletin. 2019;26(4):18-25. (In Russ.) https://doi.org/10.25207/1608-6228-2019-26-4-18-25
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