EVALUATION OF PROTEIN MARKERS OF MALIGNANT POTENTIAL IN VULVAR LICHEN SCLEROSUS

Authors

  • V. V. Dunaevska NATIONAL CANCER INSTITUTE, KYIV
  • I. M. Shakalo ACADEMIC O. M. LUKYANOVA INSTITUTE OF PEDIATRICS, OBSTETRICS AND GYNECOLOGY, KYIV
  • M. S. Krotevych NATIONAL CANCER INSTITUTE, KYIV
  • S. S. Trokhymych NATIONAL CANCER INSTITUTE, KYIV

DOI:

https://doi.org/10.11603/mcch.2410-681X.2022.i2.13212

Keywords:

vulvar lichen sclerosus, squamous cell carcinoma of the vulva, vulvar intraepithelial neoplasia, protein markers, immunohistochemical studies, p53, p16, Ki-67

Abstract

Introduction. Vulvar lichen sclerosus is a chronic T-cell inflammatory skin disease with a spectrum of clinical and pathological manifestations of unknown etiology and pathogenesis. The exact causes and pathogenesis of sclerosing lichen of the vulva are not fully known, but autoimmune, genetic, hormonal and infectious factors, as well as pathologies of the nervous system, play a role in the occurrence of this disease.

The aim of the study – immunohistochemical evaluation and study of molecular biomarkers p53, p16, Ki-67, which may indicate precancerous changes of the vulva.

Research Methods. The study involved 34 women aged 61 to 74 years, whose average age at the time of diagnosis of vulvar lichen sclerosus, vulvar intraepithelial neoplasia and leukoplakia of the vulva was (67.2±3.7) years according to the clinical databases of the National Cancer Institute and the Medical Center "Verum", with typical clinical signs of damage to the vulva. All patients underwent a biopsy of the vulva to establish the correct diagnosis, clarify the diagnosis of vulvar lichen sclerosus, and in case of diagnostic uncertainty and suspicion of neoplasia.

Results and Discussion. Biopsies performed in all patients showed a number of histological signs. In some patients (79.4 %), classic signs of vulvar lichen sclerosus were observed, sometimes with areas of ulcers that could be caused by scratches. Others (11.8 %) were diagnosed with mild and moderate dysplasia and vulvar lichen sclerosus. Squamous cell carcinoma was also diagnosed (8.8%). Immunohistochemical studies were performed in all patients based on the analysis of immunostaining of molecular markers p53, Ki-67 and p16, which are contained in the nucleus, they are well studied in high-grade squamous intraepithelial lesions and differentiated vulvar intraepithelial neoplasia.

Conclusions. Biomarkers p53, p16 and Ki-67 showed promise in retrospective tissue studies. Immunohistochemical studies not only confirmed the histological findings, but also helped determine the degree of dysplasia in the diagnosis of vulvar lichen sclerosus.

References

Day, T., Otton, G., Dennerstein, G. (2021). Erosive lichen sclerosus – a clinicopathologic subtype. Journal of Lower Genital Tract Disease, 25 (3), 255-260. https://doi.org/10.1097/LGT.0000000000000607.

Sheinis, M., Green, N., Vieira-Baptista, P. (2020). Adult vulvar lichen sclerosus: Can experts agree on the assessment of disease severity? J. Low Genit. Tract Dis., 24 (3), 295-298. DOI:10.1097/LGT.0000000000000534.

Lee, A., Fischer, G. (2018). Diagnosis and treat­ment of vulvar lichen sclerosus: An update for der­matologists”. Am. J. Clin. Dermatol., 19 (5), 695-706. DOI: 10.1007/s40257-018-0364-7.

Kirtschig, G., Becker, K., Günthert, A. (2015). Evidence-based (S3) guideline on (anogenital) lichen sclerosus. J. Eur. Acad. Dermatol. Venereol., 29, 1-43.

Hieta, N., Kurki, S., Rintala, M. (2019). Association of Vulvar Melanoma with Lichen Sclerosus. Acta Derm, Venereol., 99 (3), 339-340. DOI: 10.2340/00015555-3103.

Balbinotti, R.R., Grossi, F.S., Perez, A.V. (2021). Nonablative radiofrequency in the treatment of refractory vulvar lichen sclerosus: A case series. JAAD Case Reports, 17, 122-125. https://doi.org/10.1016/j.jdcr.2021.09.028.

Tran, D.A., Tan, X., Macri, C.J. (2019). Lichen Sclerosus: An autoimmunopathogenic and genomic enigma with emerging genetic and immune targets”. Int. J. Biol. Sci., 15 (7), 1429-1439. DOI: 10.7150/ijbs.34613.

Leis, M., Singh, A., Li, C. (2021). Risk of vulvar squamous cell carcinoma in lichen sclerosus and lichen planus: A systematic review. J Obstet. Gynaecol. Can., 19, 1701-2163. DOI: 10.1016/j.jogc.2021.09.023.

Micheletti, L., Preti, M., Radici, G. (2016). Vulvar lichen sclerosus and neoplastic transformation: a retrospective study of 976 cases. J Low Genit Tract Dis., 20, 180-183.

Lee, A., Bradford, J., & Fischer, G. (2015). Long-term management of adult vulvar lichen sclerosus: a prospective cohort study of 507 women. JAMA Dermatol., 151, 1061-1067.

Felmingham, C., Chan, L., Doyle, L.W. (2020). The vulval disease quality of life index in women with vulval lichen sclerosus correlates with clinician and symptom scores. Australas J Dermatol., 61 (2), 110-118. DOI: 10.1111/ajd.13197.

Davick, J.J., Samuelson, M., Krone, J.T. (2017). The prevalence of lichen sclerosus in patients with vulvar squamous cell carcinoma. Int. J. Gynecol. Pathol., 36 (4), 305-309. DOI: 10.1097/PGP.0000000000000341.

Halonen, P., Jakobsson, M., Heikinheimo, O. (2017). Lichen sclerosus and risk of cancer. Int. J. Cancer, 140 (9), 1998-2002. DOI: 10.1002/ijc.30621.

Bleeker, M.C., Visser, P.J., Overbeek, L.I. (2016). Lichen sclerosus: incidence and risk of vulvar squamous cell carcinoma. Cancer Epidemiol. Biomarkers Prev., 25, 1224-1230.

Carlson, B.C., Hofer, M.D., Ballek, N. (2013). Protein markers of malignant potential in penile and vulvar lichen sclerosus. J. Urol., 190 (2), 399-406. DOI: 10.1016/ j.juro.2013.01.102.

Dasgupta, S., Koljenović, S., van den Bosch, T.P.P. (2021). Evaluation of immunohistochemical markers, CK17 and SOX2, as adjuncts to p53 for the diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN). Pharmaceuticals (Basel), 14 (4), 324. DOI: 10.3390/ph14040324.

Rakislova, N., Alemany, L., Clavero, O. (2020). p53 Immunohistochemical patterns in HPV-independent squamous cell carcinomas of the vulva and the associated skin lesions: A Study of 779 Cases. Int. J. Mol. Sci., 21 8091. DOI: 10.3390/ijms21218091.

Tessier-Cloutier, B., Kortekaas, K.E., Thomp­son, E. (2020). Major p53 immunohistochemical patterns in in situ and invasive squamous cell carcinomas of the vulva and cor"relation with TP53 mutation status”. Mod. Pathol., 33 (8), 1595-1605. DOI: 10.1038/s41379-020-0524-1.

van der Avoort, I.A., van de Nieuwenhof, H.P., Otte-Höller, I., Nirmala, E., Bulten, J., Massuger, L.F., van der Laak J.A., Slootweg, P.J., de Hullu, J.A., van Kempen, L.C. (2010). High levels of p53 expression cor­relate with DNA aneuploidy in (pre)malignancies of the vulva. Hum. Pathol., 41 (10), 1475-1485. DOI: 10.1016/j.humpath.2009.12.015.

Lin, A., Day, T., Ius, Y. (2020). Anogenital high-grade squamous intraepithelial lesion comorbid with vulvar lichen sclerosus and lichen planus. J. Low Genit. Tract. Dis., 24 (3), 311-316. DOI: 10.1097/LGT.0000000000000540.

Day, T., Moore, S., Bohl, T.G. (2017). Comorbid vulvar lichen planus and lichen sclerosus. J. Low Genit. Tract Dis., 21 (3), 204-208. DOI: 10.1097/LGT.0000000000000307.

Dasgupta, S., Ewing-Graham, P.C., Swage­makers, S.M.A. (2020). Precursor lesions of vulvar squamous cell carcinoma – histology and biomarkers: A systematic review. Crit. Rev. Oncol. Hematol., 147, 102866. DOI: 10.1016/j.critrevonc.2020.102866.

Heller, D.S., Day, T., Allbritton, J.I. (2021). ISSVD Difficult Pathologic Diagnoses Committee. Diagnostic criteria for differentiated vulvar intraepithelial neoplasia and vulvar aberrant maturation. J. Low Genit. Tract Dis., 25 (1), 57-70. DOI: 10.1097/LGT.0000000000000572.

Rakislova, N., Alemany, L., Clavero, O. (2018). Differentiated vulvar intraepithelial neoplasia-like and lichen sclerosus-like lesions in HPV-associated squamous cell carcinomas of the vulva. Am. J. Surg. Pathol., 42, 828-835. 10.1097/PAS.0000000000001047.

Jeffreys, M., Jeffus, S.K., & Herfsb, M. (2018). Accentuated p53 staining in usual type vulvar dysplasia—a potential diagnostic pitfall. Pathol. Res. Practice, 214, 76-79, 10.1016/j.prp.2017.11.009.

Cohen, P.A., Anderson, L., Eva, L.J. (2019). Clinical and molecular classification of vulvar squamous pre-cancers. Int. J. Gynecol. Cancer, 1-8. 10.1136/ijgc-2018-000135.

Darragh, M.T., Colgan, T.J., Cox, J.T. (2012). The lower anogenital squamous terminology standardization project for HPV-associated lesions: Background and Consensus Recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology Arch. Pathol. Lab. Med., 10, 1266-1297. 10.5858/arpa.LGT200570.

Jin, C., & Liang, S. (2019). Differentiated vulvar intraepithelial neoplasia a brief review of clinicopathologic features. Arch. Pathol. Lab. Med., 143, 768-771. 10.5858/arpa.2018-0019-RS.

Published

2022-10-04

How to Cite

Dunaevska, V. V., Shakalo, I. M., Krotevych, M. S., & Trokhymych, S. S. (2022). EVALUATION OF PROTEIN MARKERS OF MALIGNANT POTENTIAL IN VULVAR LICHEN SCLEROSUS . Medical and Clinical Chemistry, (2), 92–99. https://doi.org/10.11603/mcch.2410-681X.2022.i2.13212

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Section

ORIGINAL INVESTIGATIONS