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Differential Expression of Ki-67 and Sex Steroid Hormone Receptors Between Genders in Peritoneal Mesothelioma

  • Original Paper
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Pathology & Oncology Research

Abstract

Gender influence on survival in mesothelioma has been observed in several large clinical series. However, this gender effect has not been investigated. Female patients often have less aggressive tumors and survive longer. However, few studies in the literature have explained the molecular basis of this finding. Understanding this difference at a molecular level may offer the hope of improving survival via hormonal manipulation.We investigate the expression of Ki-67 and sex steroid receptors; estrogen receptors (ER), progesterone receptors (PR) and androgen receptors (AR) to elucidate any pathognomonic difference that characterize this gender difference. Positive expression of markers was observed in 95% (Ki-67), 80% (ER), 100% (PR) and 65% (AR) of patients. Expression of markers between gender showed a higher Ki-67 in males (M = 1.3%, F = 0.6%), higher estrogen receptor in females (M = 0.6%, F = 1.7%) and higher progesterone receptor in females (M = 1.0%, F = 1.4%). Twenty patients were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in our peritonectomy unit. Paraffin sections of the tumor specimens were retrieved for immunohistochemical analysis. The immunostaining was performed using monoclonal mouse anti-human antibodies on an autostainer (Autostainer Plus; Dako, Inc.). The intensity of the stains were quantified using the Image-Pro Plus (IPP) 4.5 (Media Cybernetics, Silver Spring, MD). For the first time, we demonstrate the presence of sex steroid receptors in peritoneal mesothelioma. Once the exact functional effects of these receptors are understood, the use of established therapeutic options that are clinically available to target the sex steroid pathway may become a reality.

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References

  1. Boffetta P (2007) Epidemiology of peritoneal mesothelioma: a review. Ann. Oncol. 18:985–90

    Article  CAS  PubMed  Google Scholar 

  2. Robinson BW, Lake RA (2005) Advances in malignant mesothelioma. N Engl J Med. 353:1591–603

    Article  CAS  PubMed  Google Scholar 

  3. Sugarbaker PH, Welch LS, Mohamed F, Glehen OA (2003) Review of peritoneal mesothelioma at theWashington Cancer Institute. Surg Oncol Clin N Am. 12:605–621

    Article  PubMed  Google Scholar 

  4. Acherman YI, Welch LS, Bromley CM, Sugarbaker PH (2003) Clinical presentation of peritoneal mesothelioma. Tumori 89(3):269–73

    PubMed  Google Scholar 

  5. Castagneto B, Botta M, Aitini E, Spigno F, Degiovanni D, Alabiso O et al (2008) Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). Ann. Oncol. 19(2):370–3

    Article  CAS  PubMed  Google Scholar 

  6. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P et al (2003) Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21(14):2636–44

    Article  CAS  PubMed  Google Scholar 

  7. Janne PA, Wozniak AJ, Belani CP, Keohan M-L, Ross HJ, Polikoff JA et al (2005) Open-label study of pemetrexed alone or in combination with cisplatin for the treatment of patients with peritoneal mesothelioma: outcomes of an expanded access program. Clin Lung Cancer 7(1):40–6

    Article  CAS  PubMed  Google Scholar 

  8. Yan TD, Welch L, Black D, Sugarbaker PH (2007) A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma. Ann. Oncol. 18(5):827–34

    Article  CAS  PubMed  Google Scholar 

  9. Johansson L, Linden CJ (1996) Aspects of histopathologic subtype as a prognostic factor in 85 pleural mesotheliomas. Chest 109(1):109–14

    Article  CAS  PubMed  Google Scholar 

  10. Mineo TC, Ambrogi V, Pompeo E, Baldi A, Stella F, Aurea P et al (2008) The value of occult disease in resection margin and lymph node after extrapleural pneumonectomy for malignant mesothelioma. Ann Thorac Surg 85(5):1740–6

    Article  PubMed  Google Scholar 

  11. Edwards JG, Stewart DJ, Martin-Ucar A, Muller S, Richards C, Waller DA (2006) The pattern of lymph node involvement influences outcome after extrapleural pneumonectomy for malignant mesothelioma. J Thorac Cardiovasc Surg 131(5):981–7

    Article  PubMed  Google Scholar 

  12. Yan TD, Yoo D, Sugarbaker PH (2006) Significance of lymph node metastasis in patients with diffuse malignant peritoneal mesothelioma. Eur. J. Surg. Oncol. 32(9):948–53

    Article  CAS  PubMed  Google Scholar 

  13. Curran D, Sahmoud T, Therasse P, van Meerbeeck J, Postmus PE, Giaccone G (1998) Prognostic factors in patients with pleural mesothelioma: the European Organization for Research and Treatment of Cancer experience. J Clin Oncol 16(1):145–52

    CAS  PubMed  Google Scholar 

  14. Adams VI, Unni KK, Muhm JR, Jett JR, Ilstrup DM, Bernatz PE (1986) Diffuse malignant mesothelioma of pleura. Diagnosis and survival in 92 cases. Cancer 58(7):1540–51

    Article  CAS  PubMed  Google Scholar 

  15. Metintas M, Metintas S, Ucgun I, Gibbs AR, Harmanci E, Alatas F et al (2001) Prognostic factors in diffuse malignant pleural mesothelioma: effects of pretreatment clinical and laboratory characteristics. Respir. Med. 95(10):829–35

    Article  CAS  PubMed  Google Scholar 

  16. Yan TD, Popa E, Brun EA, Cerruto CA, Sugarbaker PH (2006) Sex difference in diffuse malignant peritoneal mesothelioma. Br. J. Surg. 93(12):1536–42

    Article  CAS  PubMed  Google Scholar 

  17. Antman KH, Blum RH, Greenberger JS, Flowerdew G, Skarin AT, Canellos GP (1980) Multimodality therapy for malignant mesothelioma based on a study of natural history. Am. J. Med. 68(3):356–62

    Article  CAS  PubMed  Google Scholar 

  18. Flores RM, Pass HI, Seshan VE, Dycoco J, Zakowski M, Carbone M et al (2008) Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. Journal of Thoracic & Cardiovascular Surgery 135(3):620–6

    Article  Google Scholar 

  19. Neumann V, Rutten A, Scharmach M, Muller KM, Fischer M (2004) Factors influencing long-term survival in mesothelioma patients–results of the German mesothelioma register. International Archives of Occupational & Environmental Health 77(3):191–9

    Article  CAS  Google Scholar 

  20. Rusch VW, Venkatraman ES (1999) Important prognostic factors in patients with malignant pleural mesothelioma, managed surgically. Ann. Thorac. Surg. 68(5):1799–804

    Article  CAS  PubMed  Google Scholar 

  21. Carson-Jurica MA, Schrader WT, O’Malley BW (1990) Steroid receptor family: structure and functions. Endocr. Rev. 11:201–20

    Article  CAS  PubMed  Google Scholar 

  22. McKenna NJ, Lanz RB, O’Malley BW (1999) Nuclear receptor coregulators: cellular and molecular biology. Endocr. Rev. 20:321–44

    Article  CAS  PubMed  Google Scholar 

  23. Sugarbaker PH (1995) Peritonectomy procedures. Ann. Surg. 221:29–42

    CAS  PubMed  Google Scholar 

  24. Garcia-Carbonero R, Paz-Ares L (2006) Systemic chemotherapy in the management of malignant peritoneal mesothelioma. Eur. J. Surg. Oncol. 32(6):676–81

    Article  CAS  PubMed  Google Scholar 

  25. Thomas Scholzen JG (2000) The Ki-67 protein: From the known and the unknown. J Cell Physiol 182(3):311–22

    Article  Google Scholar 

  26. Smolle J, Hoffmann-Wellenhof R, Soyer H-P, Stettner H, Kerl H (1989) Nuclear Size and Shape Parameters Correlate with Proliferative Activity in Cutaneous Melanocytic Tumors. J Invest Dermatol 93(1):178–82

    Article  CAS  PubMed  Google Scholar 

  27. Gao X, Loggie BW, Nawaz Z (2002) The roles of sex steroid receptor coregulators in cancer. Molecular Cancer. 1:7

    Article  PubMed  Google Scholar 

  28. Schiff R, Saw F (2002) The importance of the estrogen receptor in breast cancer. In: Pasqualini JR (ed) Breast cancer: prognosis, treatment, and prevention. Marcel Dekker, New York, NY, pp 149–86

    Google Scholar 

  29. Rowan BG, O’Malley BW (2000) Progesterone receptor coactivators. Steroids 65(10–11):545–9

    Article  CAS  PubMed  Google Scholar 

  30. Heemers HV, Tindall DJ (2007) Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocr. Rev. 28(7):778–808

    Article  CAS  PubMed  Google Scholar 

  31. Ryan PD, Goss PE (2008) The emerging role of the insulin-like growth factor pathway as a therapeutic target in cancer. Oncologist 13(1):16–24

    Article  CAS  PubMed  Google Scholar 

  32. Barnetson RJ, Burnett RA, Downie I, Harper CM, Roberts F (2006) Immunohistochemical analysis of peritoneal mesothelioma and primary and secondary serous carcinoma of the peritoneum: antibodies to estrogen and progesterone receptors are useful. Am. J. Clin. Pathol. 125(1):67–76

    CAS  PubMed  Google Scholar 

  33. Horita K, Inase N, Miyake S, Formby B, Toyoda H, Yoshizawa Y (2001) Progesterone induces apoptosis in malignant mesothelioma cells. Anticancer Res. 21(6A):3871–4

    CAS  PubMed  Google Scholar 

  34. Sawh RN, Malpica A, Deavers MT, Liu J, Silva EG (2003) Benign cystic mesothelioma of the peritoneum: a clinicopathologic study of 17 cases and immunohistochemical analysis of estrogen and progesterone receptor status. Hum. Pathol. 34(4):369–74

    Article  CAS  PubMed  Google Scholar 

  35. Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J et al (1989) A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med 320(8):479–84

    Article  CAS  PubMed  Google Scholar 

  36. Elledge RM, Allred DC (2004) Clinical aspects of estrogen and progesterone receptors. In: Harris JR, Lippman ME, Morrow M (eds) Diseases of the Breast, 3rd edn. Lippincott Williams and Wilkins, Philadelphia, PA, pp 603–17

    Google Scholar 

  37. Cui X, Schiff R, Arpino G, Osborne CK, Lee AV (2005) Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol 23(30):7721–35

    Article  CAS  PubMed  Google Scholar 

  38. Smith CL, O'Malley BW (2004) Coregulator Function: A Key to Understanding Tissue Specificity of Selective Receptor Modulators. Endocr. Rev. 25(1):45–71

    Article  CAS  PubMed  Google Scholar 

  39. d'Ancona FCH, Debruyne FMJ (2005) Endocrine approaches in the therapy of prostate carcinoma. Hum Reprod Update 11(3):309–17

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We express our gratitude to Dr. Robert Markham, Obstetrics and Gynaecology, Faculty of Medicine, University of Sydney, for his kind assistance and the laboratory space provided to us for to perform the immunostaining.

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Authors and Affiliations

  1. UNSW Department of Surgery, Cancer Research Laboratory, St George Hospital, Kogarah, Sydney, NSW 2217, Australia

    Terence C. Chua, Peng Yao, Javed Akther, Lawrence Young, Tristan D. Yan & David L. Morris

  2. Discipline of Pathology, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW, 2006, Australia

    Shisan Bao

  3. Department of Pathology, Prince of Wales Hospital, Randwick, Sydney, NSW, 2031, Australia

    Ushma Samaraweera

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  1. Terence C. Chua
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  2. Peng Yao
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  3. Javed Akther
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  8. David L. Morris
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Correspondence to David L. Morris.

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Synopsis

Higher expression of Ki-67 protein, lower ER and PR in peritoneal mesothelioma tumor of males compared to females. We provide preliminary evidence of the possible involvement of sex steroid receptors in the cancer biology of peritoneal mesothelioma.

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Chua, T.C., Yao, P., Akther, J. et al. Differential Expression of Ki-67 and Sex Steroid Hormone Receptors Between Genders in Peritoneal Mesothelioma. Pathol. Oncol. Res. 15, 671–678 (2009). https://doi.org/10.1007/s12253-009-9170-0

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  • DOI: https://doi.org/10.1007/s12253-009-9170-0

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