Top

Published in:

Open Access 01-05-2019 | Lichen Sclerosus Et Atrophicus | Gynecologic Oncology

Tumor cell-specific Serpin A1 expression in vulvar squamous cell carcinoma

Authors: Maria Lagerstedt, R. Huotari-Orava, R. Nyberg, L. Nissinen, M. Farshchian, S.-L. Laasanen, E. Snellman, J. U. Mäenpää, V.-M. Kähäri

Published in: Archives of Gynecology and Obstetrics | Issue 5/2019

Abstract

Purpose

The two main etiological factors for vulvar squamous cell carcinoma (vSCC) are the vulvar dermatosis lichen sclerosus (LS) and high-risk human papillomavirus (hrHPV). Serpin A1 (α1-antitrypsin) is a serine protease inhibitor, which plays a role in the tumorigenesis of various cancer types. The aim of the study was to evaluate the expressions of Serpin A1 in LS, premalignant vulvar lesions, and vSCC using immunohistochemistry (IHC) and serum analysis, and to compare Serpin A1 stainings to the tumor markers p53 and p16.

Methods

In total, 120 samples from 74 patients were studied with IHC for Serpin A1, p53 and p16: 18 normal vulvar skin, 53 LS, 9 premalignant vulvar lesions (dVIN/HSIL) and 40 vSCC samples. Serum concentrations of Serpin A1 were analyzed from 30 LS, 44 vSCC and 10 control patients. Expressions were compared to clinical data.

Results

Tumor cell-specific Serpin A1 overexpression was detected in 88% of vSCC samples, independent of the etiology. The intensity of Serpin A1 expression was significantly higher in vSCC than in healthy vulvar skin, LS, or premalignant vulvar lesions. Serpin A1 showed an association with p53 positivity. No difference in overall survival was found between Serpin A1-, p53-, or p16-positive vSCC patients. Serum concentrations of Serpin A1 were equal in the LS, vSCC, and control groups.

Conclusion

Tumor cell-specific Serpin A1 overexpression is a potential biomarker in vSCC.

Dong F, Kojiro S, Darrell RB, Growdon WB, Oliva E (2015) Squamous cell carcinoma of the vulva: a subclassification of 97 cases by clinicopathologic, immunohistochemical, and molecular features (p16, p53, and EGFR). Am J Surg Pathol 39:1045–1053CrossRefPubMed

Del Pino M, Rodriguez-Carunchio L, Ordi J (2013) Pathways of vulvar intraepithelial neoplacia and squamous cell carcinoma. Histopathology 62:161–175CrossRefPubMed

Singh N, Leen SL, Han G, Faruqi A, Kokka F, Rosenthal A et al (2015) Expanding the morphologic spectrum of differentiated VIN (dVIN) through detailed mapping of cases with p53 loss. Am J Surg Pathol 39:52–60CrossRefPubMed

Cheng AS, Karnezis AN, Jordan S, Sighn N, McAlpine JN, Gilks CG (2016) p16 immunostaining allows for accurate subclassification of vulvar squamous cell carcinoma into HPV associated and HPV independent cases. Int J Gynecol Pathol 35:385–393CrossRefPubMed

Carlson BC, Hofer MD, Ballek N, Yang XJ, Meeks JJ, Gonzalez CM (2013) Protein markers of malignant potential in penile and vulvar lichen sclerosus. J Urol 190:399–406CrossRefPubMed

Kwon CH, Park HJ, Lee JR, Kim HK, Jeon TY, Jo HJ et al (2014) Serpin peptidase inhibitor clade A member 1 is a biomarker of poor prognosis in gastric cancer. Br J Cancer 111:1993–2002CrossRefPubMedPubMedCentral

Ehlers MR (2014) Immuno-modulating effects of alpha-1 antitrypsin. Biol Chem 10:1187–1193

Nissinen L, Farshchian M, Riihilä P, Kähäri VM (2016) New perspectives on role of tumor microenviroment in progression of cutaneus squamous cell carcinoma. Cell Tissue Res 365:691–702CrossRefPubMed

Higashiyama M, Doi O, Kodama K, Yokouchi H, Tateishi R (1992) An evaluation of the prognostic significance of alpha-1-antitrypsin expression in adenocarcinomas of the lung: an immunohistochemical analysis. Br J Cancer 65:300–302CrossRefPubMedPubMedCentral

10.

Kwon CH, Park HJ, Choi JH, Lee JR, Kim HK, Jo HJ et al (2015) Snail and Serpin A1 promote tumor progression and predict prognosis in colorectal cancer. Oncotarget 6:20312–20326PubMedPubMedCentral

11.

Normandin K, Péant B, Le Page C, de Ladurantaye M, Ouellet V, Tonin PN et al (2010) Protease inhibitor SERPINA1 expression in epithelial ovarian cancer. Clin Exp Metastasis 27:55–69CrossRefPubMed

12.

Kloth JN, Gorter A, Fleuren GJ, Oosting J, Uljee S, ter Haar N et al (2008) Elevated expression of Serpin A1 and Serpin A3 in HLA-positive cervical carcinoma. J Pathol 215:222–230CrossRefPubMed

13.

Farshchian M, Kivisaari A, Ala-aho R, Riihilä P, Kallajoki M, Grénman R et al (2011) Serpin peptidase inhibitor clade A member 1 (Serpin A1) is a novel biomarker for progression of cutaneous squamous cell carcinoma. Am J Pathol 179:1110–1119CrossRefPubMedPubMedCentral

14.

Joshi N, Johnson LL, Wei WQ, Abnet CC, Dong ZW, Taylor PR et al (2006) Gene expression differences in normal esophageal mucosa associated with regression amd progression of mild and moderate squamous dysplasia in a high-risk Chinese population. Cancer Res 6:6851–6860CrossRef

15.

Zhao J, Fan YX, Yang Y, Liu DL, Wu K, Wen FB et al (2015) Identification of potential plasma biomarkers for esophageal squamous cell carcinoma by a proteomic method. Int J Exp Pathol 8:1535–1544

16.

Yang J, Xiong X, Wang X, Guo B, He K, Huang C (2010) Identification of peptide regions of SERPINA1 and ENOSF1 and their protein expression as potential serum biomarkers for gastric cancer. Tumor Biol 36:5109–5118CrossRef

17.

El-Akawi ZJ, Al-Hindawi FK, Bashir NA (2008) Alpha-1 antitrypsin (alpha1-AT) plasma levels in lung, prostate and breast cancer patients. Neuro Endocrinol Lett 29:482–484PubMed

18.

Topic A, Ljujic M, Petrovic-Stanojevic N, Dopudja-Pantic V, Radojkovic D (2011) Phenotypes and serum levels of alpha-1-antitrypsin in lung cancer. J BUON 16:672–676PubMed

19.

Pérez-Holanda S, Blanco I, Menéndez M, Rodrigo L (2014) Serum concentration of alpha-1 antitrypsin is significantly higher in colorectal cancer patients than in healthy controls. BMC Cancer 14:355CrossRefPubMedPubMedCentral

20.

Duplantier MM, Lamant L, Sabourdy F, de Reynies A, Delsol G, Espinos E (2006) Serpin A1 is overexpressed in ALK⁺ anaplastic large cell lymphoma and its expression correlates with extranodal dissemination. Leukemia 20:1848–1854CrossRefPubMed

21.

Shirasuna K, Sugiyama M, Watatani K, Morioka S, Havashido Y (1987) Serum alpha-1-antitrypsin in patients with malignant tumors occurring in the oral region. Int J Oral Maxillofac Surg 16:516–520CrossRefPubMed

22.

Sun Z, Yang P (2004) Role of imbalance between neutrofil elastase and α1-antitrypsin in cancer development and progression. Lancet Oncol 5:182–190CrossRefPubMed

23.

Chan HJ, Li H, Liu Z, Yuan YC, Mortimer J, Chen S (2015) SERPINA1 is a direct estrogen receptor target gene and a predictor of survival in breast cancer patients. Oncotarget 6:25815–25827PubMedPubMedCentral

24.

Li Y, Miao L, Yu M, Shi M, Wang Y, Yang J et al (2017) α1-antitrypsin promotes lung adenocarcinoma metastasis through upregulating fibronectin expression. Int J Oncol 50:1955–1964CrossRefPubMedPubMedCentral

25.

Bodelon C, Madeleine MM, Johnson LG, Du Q, Galloway DA, Malkki M et al (2014) Genetic variation in the TLR and NF-κB genetic pathways and cervical and vulvar cancer risk: a population-based case–control study. Int J Cancer 15:437–444CrossRef

26.

Terlou A, Santegoets LA, van der Meijden WI, Heijmans-Antonissen C, Swagemakers SM, van der Spek PJ et al (2012) An autoimmune phenotype in vulvar lichen sclerosus and lichen planus: a Th1 response and high levels of microRNA-155. J Invest Dermatol 132:658–666CrossRefPubMed

27.

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

28.

Mangino G, Chiantore MV, Iuliano M, Fiorucci G, Romeo G (2016) Inflammatory microenvironment and human papilloma-induced carcinogenesis. Cytokine Growth Factor Rev 30:103–111CrossRefPubMed

29.

Shakya R, Tarulli GA, Sheng L, Lokman NA, Ricciardelli C, Pishas KI et al (2017) Mutant p53 upregulates alpha-1 antitrypsin expression and promotes invasion in lung cancer. Oncogene 36:4469–4480CrossRefPubMed

30.

Sadalla JC, Lourenço SV, Sotto MN, Baracat EC, Carvalho JP (2011) Claudin and p53 expression in vulvar lichen sclerosus and squamous-cell carcinoma. J Clin Pathol 64:853–857CrossRefPubMed

31.

Liegl B, Regauer S (2006) p53 immunostaining in lichen sclerosus is related to ischaemic stress and is not a marker of differentiated vulvar intraepithelial neoplasia (d-VIN). Histopathology 48:268–274CrossRefPubMed

32.

Nooij LS, ter Haar NT, Ruano D, Rakislova N, van Wezel T, Smit VT et al (2017) Genomic characterization of vulvar (pre) cancers identifies distinct molecular subtypes with prognostic significance. Clin Cancer Res 23:6781–6789CrossRefPubMed

Title: Tumor cell-specific Serpin A1 expression in vulvar squamous cell carcinoma
Authors: Maria Lagerstedt
R. Huotari-Orava
R. Nyberg
L. Nissinen
M. Farshchian
S.-L. Laasanen
E. Snellman
J. U. Mäenpää
V.-M. Kähäri
Publication date: 01-05-2019
Publisher: Springer Berlin Heidelberg
Keyword: Lichen Sclerosus Et Atrophicus
Published in: Archives of Gynecology and Obstetrics / Issue 5/2019
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-018-5015-y

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Tumor cell-specific Serpin A1 expression in vulvar squamous cell carcinoma

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 5/2019

Effectiveness of the cervical pessary for the prevention of preterm birth in singleton pregnancies with a short cervix: a meta-analysis of randomized trials

Endoscopic surgery: talent or training?

Spatulas for entrapment of the after-coming head during vaginal breech delivery

Laparoscopic pectopexy: a follow-up cyclic biomechanical analysis determining time to functional stability

Uterus transplantation: advantages and disadvantages of a deceased donor

Downregulation of miR-4443 and miR-5195-3p in ovarian cancer tissue contributes to metastasis and tumorigenesis