Decreased NK cell activity after partial vulvectomy in pregnant patient with vulvar intraepithelial neoplasia 3 (VIN3)

Malgorzata Jerzak 1  ,  
Monika Ohams 2,  
Department of Gynecology and Gynecological Oncology, Military Institute of Medicine, Warsaw, Poland
Department of Clinical Immunology, Transplantation Institute, University Medical School, Warsaw, Poland
Ann Agric Environ Med 2017;24(3):459–463
Introduction and objective:
The study presents the problem of immune disturbances in pregnant women with vulvar carcinoma in situ (VIN3).

Material and Methods:
NK cell and T reg activity in the study patient were analysed using flow cytometry.

Decreased NK cell activity and but increased T reg activity were observed after vulvectomy, with subsequent successful pregnancy outcome.

Although vulvar cancer may influence immune cell activity, this issue merits further study.

Malgorzata Jerzak   
Department of Gynecology and Gynecological Oncology, Military Institute of Medicine, Warsaw, Poland
1. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on preamature cancer death. CA Cancer J Clin 2011; 61:212–36.
2. McCluggage WG. Premalignant lesions of the lower female genital tract: cervix, vagina and vulva. Pathology 2013; 45: 214–28.
3. Jones RW, Baranyai J, Stables S. Trends in squamous cell carcinoma of the vulva: the influence of vulvar intraepithelial neoplasia. Obstet Gynecol. 1997; 90: 448–52.
4. Joura EA, Lösch A, Haider-Angeler MG, Breitenecker G, Leodolter S. Trends in vulvar neoplasia. Increasing incidence of vulvar intraepithelial neoplasia and squamous cell carcinoma of the vulva in young women. J Reprod Med. 2000; 45: 613–5.
5. Judson PL, Habermann EB, Baxter NN, Durham SB, Virnig BA. Trends in the incidence of invasive and in situ vulvar carcinoma. Obstet Gynecol. 2006; 107: 1018–22.
6. Baandrup L, Varbo A, Munk C, Johansen C, Frisch M, Kjaer SK. In situ andinvasive squamous cell carcinoma of the vulva in Denmark 1978–2007 – a nationwide population-based study. Gynecol Oncol. 2011; 122: 45–9.
7. van Seters M, van Beurden M, de Craen AJ. Is the assumed natural history of vulvar intraepithelial neoplasia III based on enough evidence? A systematic review of 3322 published patients. Gynecol Oncol. 2005; 97: 645–51.
8. Ogunleye D, Lewin SN, Huettner P, Herzog TJ. Recurrent vulvar carcinoma in pregnancy. Gynecol Oncol. 2004; 95: 400–1.
9. Van Seters M, Beckmann I, Heijmans-Antonissen C, van Beurden M, Rwing PC, Zijlstra FJ, Helmerhorst TJM, KlrinJan A. Disturbed Patterns of Immunocompetent Cells in Usual-Type Vulvar Intraepithelial Neoplasia. Cancer Res. 2008; 68: 6617–6622.
10. Robbins SH, Bessoi G, Cornillon A, Zucchini N, Rupp B, Ruzsics Z, Sacher T, Tomasello E, Vivier E, Koszinowski UH, Dalod M.Natural killer cells promote early CD8 T cell responses against cytomegalovirus. PLoS Pathog. 2007; 3: 1152–64.
11. Sznurkowski JJ, Żawrocki A, Emerich J, Sznurkowska K, Biernat W. Expression of indoleamine 2,3-dioxygenase predicts shorter survival in patients with vulvar squamous cell carcinoma (vSCC) not influencing on the recruitmrnt of FOXP3-expressing regulatory T cells in cancer nests. Gynecol Oncol. 2011; 122: 307–312.
12. Ntrivalas EI, Kwak-Kim JY, Gilman-Sachs A, Chung-Bang H, Ng SC, Beaman KD, et al. Status of peripheral blood natural killer cells in women with recurrent spontaneous abortions and infertility of unknown aetiology. Hum Reprod. 2001; 16: 855–861.
13. Aoki K, Kajiura S, Matsumoto Y, OgasawaraM, Okada M, Yagami Y, et al. Preconceptional natural- killer- cell activity as a predictor of miscarriage. Lancet 1995; 345: 1340–1342.
14. Santoni A, Carlino C, Stabile H, Gismondi A. Mechanisms underlying recruitment and accumulation of decidual NK cells in uterus during pregnancy. Am J Reprod Immunol. 2008; 59: 417–424.
15. Yamada H, Morikawa M, Kato EH, Shimada S, Kobashi G, Minakami H. Pre-conceptional natural killer cell activity and percentage as predictors of biochemical pregnancy and spontaneous abortion with normal chromosome karyotype. Am J Reprod Immunol. 2003; 50: 351–4.
16. King K, Smith S, Chapman M, Sacks G. Detailed analysis of peripheral blood natural killer (NK) cells in women with recurrent miscarriage. Hum Reprod. 2010; 25: 52–58.
17. Jerzak M, Kniotek M, Mrozek J, Górski A, Baranowski W. Sildenafil citrate decreased NK cell activity and enhanced chance of successful pregnancy in women with a history of recurrent miscarriage. Fertil Steril. 2008; 90: 1848–1853.
18. Jones RW, Rowan DM. Spontaneous regression of vulvar intraepithelial neoplasia 2–3. Obstet Gynecol. 2000; 96: 470–472.
19. Jones RW, Rowan DM, Stewart AW. Vulvar intraepithelial neoplasia: aspects of natural history and outcome in 405 women. Obstet Gynecol. 2005; 106: 1319–26.
20. Maclean AB. Vulval cancer: prevention and screening. Best Pract Res Clin Obstet Gynaecol. 2006; 20: 379–95.
21. Molling JW, de Gruijl TD, Glim J, Moreno M, Rozendaal L, Meijer CJ, van den Eartwegh AJ, Scheper RJ, von Blomberg ME, Bontkes HJ. CD4(+)CD25hi regulatory T-cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasia. Int J Cancer 2007; 121: 1749–1755.
22. Kojima S, Kawana K, Tomio K, Yamashita A, Taguchi A, Miura S, Adachi K, Nagamatsu T, Nagasaka K, Matsumoto Y, Arimoto T, Oda K, Wada-Hiraike O, Yano T, Taketani Y, Fujii T, Schust DJ, Kozuma S. The prevalence of cervical regulatory T cells in HPV-related cervical intraepithelial neoplasia (CIN) correlates inversely with spontaneous regression of CIN. Am J Reprod Immunol. 2013; 69: 134–141.