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Increased osteopontin expression is associated with progression from vulvar precancerous lesions to vulvar squamous cell carcinoma

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Vulvar squamous cell carcinoma (VSCC) contributes to about 3–5 % of all gynecological cancers. Vulvar intraepithelial neoplasia (VIN) and vulvar lichen sclerosus (VLS) are regarded as precancerous lesions. Early detection and treatment of precancerous lesions may prevent development of VSCC. Osteopontin (OPN) has been shown to be involved in many physiological and pathological processes, such as tumor progression, by promoting cancer cell invasion and metastasis. As a result of these findings, OPN has been described as a potential marker for tumor progression in some malignancies. In this study, we investigated the expression of OPN in vulvar tissue specimens and compared its expression between different histopathological grades.

Methods

In the present study, the expression patterns of OPN in 80 paraffin-embedded tissue specimens, including 25 VSCC samples, 21 VIN lesions and 21 VLS, in addition to 13 normal vulvar samples, were examined by the immunohistochemical method and chromogenic in situ hybridization.

Results

The intensity of OPN expression steadily increased according to the pathological grades. In addition, OPN staining was found in the extracellular matrix in VSCC.

Conclusions

Expression levels of OPN increased from VLS and VIN to VSCC, and steadily increased with the pathological stage of VSCC. Our results suggest that OPN may be associated with the progression of VSCC.

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References

  1. van de Nieuwenhof HP, van der Avoort IA, de Hullu JA (2008) Review of squamous premalignant vulvar lesions. Crit Rev Oncol Hematol 68(2):131–156. doi:10.1016/j.critrevonc.2008.02.012 S1040-8428(08)00052-8 [pii]

    Article  PubMed  Google Scholar 

  2. de Hullu JA, van der Zee AG (2006) Surgery and radiotherapy in vulvar cancer. Crit Rev Oncol Hematol 60(1):38–58. doi:10.1016/j.critrevonc.2006.02.008

    Article  PubMed  Google Scholar 

  3. Hoevenaars BM, van der Avoort IA, de Wilde PC, Massuger LF, Melchers WJ, de Hullu JA, Bulten J (2008) A panel of p16(INK4A), MIB1 and p53 proteins can distinguish between the 2 pathways leading to vulvar squamous cell carcinoma. Int J Cancer 123(12):2767–2773. doi:10.1002/ijc.23857

    Article  CAS  PubMed  Google Scholar 

  4. van der Avoort IA, Shirango H, Hoevenaars BM, Grefte JM, de Hullu JA, de Wilde PC, Bulten J, Melchers WJ, Massuger LF (2006) Vulvar squamous cell carcinoma is a multifactorial disease following two separate and independent pathways. Int J Gynecol Pathol 25(1):22–29 00004347-200601000-00002[pii]

    Article  PubMed  Google Scholar 

  5. van der Avoort IA, van der Laak JA, Otte-Holler I, van de Nieuwenhof HP, Massuger LF, de Hullu JA, van Kempen LC (2010) The prognostic value of blood and lymph vessel parameters in lichen sclerosus for vulvar squamous cell carcinoma development: an immunohistochemical and electron microscopy study. Am J Obstet Gynecol. doi:10.1016/j.ajog.2010.02.002 S0002-9378(10)00163-8 [pii]

    PubMed  Google Scholar 

  6. Sanders RJ, Mainiero F, Giancotti FG (1998) The role of integrins in tumorigenesis and metastasis. Cancer Invest 16(5):329–344. doi:10.3109/07357909809084653

    Article  CAS  PubMed  Google Scholar 

  7. Forootan SS, Foster CS, Aachi VR, Adamson J, Smith PH, Lin K, Ke Y (2006) Prognostic significance of osteopontin expression in human prostate cancer. Int J Cancer 118(9):2255–2261. doi:10.1002/ijc.21619

    Article  CAS  PubMed  Google Scholar 

  8. Denhardt DT, Noda M, O’Regan AW, Pavlin D, Berman JS (2001) Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival. J Clin Invest 107(9):1055–1061. doi:10.1172/jci12980

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. El-Tanani MK, Campbell FC, Kurisetty V, Jin D, McCann M, Rudland PS (2006) The regulation and role of osteopontin in malignant transformation and cancer. Cytokine Growth Factor Rev 17(6):463–474. doi:10.1016/j.cytogfr.2006.09.010 S1359-6101(06)00059-1 [pii]

    Article  CAS  PubMed  Google Scholar 

  10. Sodek J, Da Silva Batista AP, Zohar R (2006) Osteopontin and mucosal protection. J Dent Res 85(5):404–415

    Article  CAS  PubMed  Google Scholar 

  11. Wang KX, Denhardt DT (2008) Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor Rev 19(5–6):333–345. doi:10.1016/j.cytogfr.2008.08.001

    Article  CAS  PubMed  Google Scholar 

  12. Yang L, Wei L, Zhao W, Wang X, Zheng G, Zheng M, Song X, Zuo W (2012) Down-regulation of osteopontin expression by RNA interference affects cell proliferation and chemotherapy sensitivity of breast cancer MDA-MB-231 cells. Mol Med Report 5(2):373–376. doi:10.3892/mmr.2011.679

    CAS  Google Scholar 

  13. Shojaei F, Scott N, Kang X, Lappin PB, Fitzgerald AA, Karlicek S, Simmons BH, Wu A, Lee JH, Bergqvist S, Kraynov E (2012) Osteopontin induces growth of metastatic tumors in a preclinical model of non-small lung cancer. J Exp Clin Cancer Res 31:26. doi:10.1186/1756-9966-31-26

    Article  CAS  PubMed  Google Scholar 

  14. Tilli TM, Mello KD, Ferreira LB, Matos AR, Accioly MT, Faria PA, Bellahcene A, Castronovo V, Gimba ER (2012) Both osteopontin-c and osteopontin-b splicing isoforms exert pro-tumorigenic roles in prostate cancer cells. Prostate 72(15):1688–1699. doi:10.1002/pros.22523

    Article  CAS  PubMed  Google Scholar 

  15. Wai PY, Kuo PC (2008) Osteopontin: regulation in tumor metastasis. Cancer Metastasis Rev 27(1):103–118. doi:10.1007/s10555-007-9104-9

    Article  CAS  PubMed  Google Scholar 

  16. Lin CK, Tsai WC, Lin YC, Hueng DY (2012) Osteopontin predicts the behaviour of atypical meningioma. Histopathology 60(2):320–325. doi:10.1111/j.1365-2559.2011.04085.x

    Article  PubMed  Google Scholar 

  17. Zhou Y, Dai DL, Martinka M, Su M, Zhang Y, Campos EI, Dorocicz I, Tang L, Huntsman D, Nelson C, Ho V, Li G (2005) Osteopontin expression correlates with melanoma invasion. J Invest Dermatol 124(5):1044–1052. doi:10.1111/j.0022-202X.2005.23680.x JID23680 [pii]

    Article  CAS  PubMed  Google Scholar 

  18. Rangel J, Nosrati M, Torabian S, Shaikh L, Leong SP, Haqq C, Miller JR 3rd, Sagebiel RW, Kashani-Sabet M (2008) Osteopontin as a molecular prognostic marker for melanoma. Cancer 112(1):144–150. doi:10.1002/cncr.23147

    Article  PubMed  Google Scholar 

  19. Chang PL, Harkins L, Hsieh YH, Hicks P, Sappayatosok K, Yodsanga S, Swasdison S, Chambers AF, Elmets CA, Ho KJ (2008) Osteopontin expression in normal skin and non-melanoma skin tumors. J Histochem Cytochem 56(1):57–66. doi:10.1369/jhc.7A7325.2007 jhc.7A7325.2007 [pii]

    Article  CAS  PubMed  Google Scholar 

  20. Buback F, Renkl AC, Schulz G, Weiss JM (2009) Osteopontin and the skin: multiple emerging roles in cutaneous biology and pathology. Exp Dermatol 18(9):750–759. doi:10.1111/j.1600-0625.2009.00926.x EXD926 [pii]

    Article  CAS  PubMed  Google Scholar 

  21. Briese J, Schulte HM, Bamberger CM, Loning T, Bamberger AM (2006) Expression pattern of osteopontin in endometrial carcinoma: correlation with expression of the adhesion molecule CEACAM1. Int J Gynecol Pathol 25(2):161–169. doi:10.1097/01.pgp.0000189243.49522.ae 00004347-200604000-00008 [pii]

    Article  PubMed  Google Scholar 

  22. Song JY, Lee JK, Lee NW, Yeom BW, Kim SH, Lee KW (2009) Osteopontin expression correlates with invasiveness in cervical cancer. Aust N Z J Obstet Gynaecol 49(4):434–438. doi:10.1111/j.1479-828X.2009.01027.x AJO1027 [pii]

    Article  PubMed  Google Scholar 

  23. Davidson B, Holth A, Moripen L, Trope CG, Ie Shih M (2011) Osteopontin expression in ovarian carcinoma effusions is related to improved clinical outcome. Hum Pathol 42(7):991–997. doi:10.1016/j.humpath.2010.10.013 S0046-8177(10)00405-3 [pii]

    Article  CAS  PubMed  Google Scholar 

  24. Zhang J, Takahashi K, Takahashi F, Shimizu K, Ohshita F, Kameda Y, Maeda K, Nishio K, Fukuchi Y (2001) Differential osteopontin expression in lung cancer. Cancer Lett 171(2):215–222 S0304383501006073 [pii]

    Article  CAS  PubMed  Google Scholar 

  25. Atai NA, Bansal M, Lo C, Bosman J, Tigchelaar W, Bosch KS, Jonker A, De Witt Hamer PC, Troost D, McCulloch CA, Everts V, Van Noorden CJ, Sodek J (2011) Osteopontin is up-regulated and associated with neutrophil and macrophage infiltration in glioblastoma. Immunology 132(1):39–48. doi:10.1111/j.1365-2567.2010.03335.x IMM3335 [pii]

    Article  CAS  PubMed  Google Scholar 

  26. Imano M, Okuno K, Itoh T, Ishimaru E, Satou T, Shiozaki H (2010) Increased osteopontin-positive macrophage expression in colorectal cancer stroma with synchronous liver metastasis. World J Surg 34(8):1930–1936. doi:10.1007/s00268-010-0582-5

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Medical Research Projects of Shandong Province (No. 2007HZ059). We thank Dr. Edward C. Mignot, Shandong University, for linguistic advice.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Traditional Chinese Integrated Western Medicine, Qi Lu Hospital, Shandong University, Jinan, 250012, People’s Republic of China

    Zhihong Wu, Xiaodan Zhang & Shuling Li

  2. Department of Medical Biochemistry and Biophysics, Umea University, 90187, Umea, Sweden

    Yue Shen

  3. Qi Lu Children’s Hospital, Shandong University, Jinan, 250022, People’s Republic of China

    Kebo Gong & Zhihua Wu

  4. Department of Pathology, Qi Lu Hospital, Shandong University, Jinan, 250012, People’s Republic of China

    Tingguo Zhang

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  1. Zhihong Wu
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  2. Yue Shen
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  4. Zhihua Wu
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Correspondence to Shuling Li.

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Wu, Z., Shen, Y., Gong, K. et al. Increased osteopontin expression is associated with progression from vulvar precancerous lesions to vulvar squamous cell carcinoma. Arch Gynecol Obstet 289, 637–644 (2014). https://doi.org/10.1007/s00404-013-3009-3

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  • DOI: https://doi.org/10.1007/s00404-013-3009-3

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