SOD2 immunoexpression predicts lymph node metastasis in penile cancer

BMC Clinical Pathology

Gustavo C Guimarães²  Luisa L Villa⁶  Fernando A Soares⁵  Isabela W da Cunha⁵  Ademar Lopes²  Maria C Costa⁴  Maria A Andreoli⁴  Adhemar Longatto-Filho¹  Walter H da Costa²  Enrique Boccardo³  José H Fregnani³  Lara Termini⁴ 

[1] Molecular Oncology Research Center, Barretos Cancer Hospital, Pio XII Foundation, Barretos, Rua Antenor Duarte Villela, 1331, Barretos, 14784-400, Brazil;Pelvic Surgery Department, A. C. Camargo Cancer Center, Rua Prof. Antônio Prudente 211, São Paulo, 01509-010, Brazil;Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1374 - Ed. Biomédicas II, Cidade Universitária, São Paulo, 05508-900, Brazil;Santa Casa de São Paulo, INCT-HPV at Santa Casa Research Institute, School of Medicine, Rua Marquês de Itú, 381, São Paulo, 01223-001, Brazil;Department of Anatomic Pathology, A. C. Camargo Cancer Center, Rua Prof. Antônio Prudente 109, São Paulo, 01509-900, Brazil;Department of Radiology and Oncology, School of Medicine, University of São Paulo and Cancer Institute of the State of São Paulo, ICESP, Av Dr Arnaldo 250, São Paulo, 01246-000, Brazil

关键词: Lymph node metastasis;    Superoxide Dismutase-2;    Penile cancer;   

Others  :  1135361
DOI  :  10.1186/s12907-015-0003-7

 received in 2014-11-10, accepted in 2015-02-09,  发布年份 2015

【 摘 要 】

Background

Superoxide dismutase-2 (SOD2) is considered one of the most important antioxidant enzymes that regulate cellular redox state in normal and tumorigenic cells. Overexpression of this enzyme in lung, gastric, colorectal, breast cancer and cervical cancer malignant tumors has been observed. Its relationship with inguinal lymph node metastasis in penile cancer is unknown.

Methods

SOD2 protein expression levels were determined by immunohistochemistry in 125 usual type squamous cell carcinomas of the penis from a Brazilian cancer center. The casuistic has been characterized by means of descriptive statistics. An exploratory logistic regression has been proposed to evaluate the independent predictive factors of lymph node metastasis.

Results

SOD2 expression in more than 50% of cells was observed in 44.8% of primary penile carcinomas of the usual type. This expression pattern was associated with lymph node metastasis both in the uni and multivariate analysis.

Conclusions

Our results indicate that SOD2 expression predicts regional lymph node metastasis. The potential clinical implication of this observation warrants further studies.

【 授权许可】

   
2015 Termini et al.; licensee BioMed Central.

【 参考文献 】

• [1]Guimarães GC, Rocha RM, Zequi SC, Cunha IW, Soares FA: Penile cancer: epidemiology and treatment. Curr Oncol Rep 2011, 13(3):231-9.
• [2]Guimarães GC, Lopes A, Campos RS, Zequi S d C, Leal ML, Carvalho AL, et al.: Front pattern of invasion in squamous cell carcinoma of the penis: new prognostic factor for predicting risk of lymph node metastases. Urology 2006, 68(1):148-53.
• [3]Chaux A, Caballero C, Soares F, Guimarães GC, Cunha IW, Reuter V, et al.: The prognostic index: a useful pathologic guide for prediction of nodal metastases and survival in penile squamous cell carcinoma. Am J Surg Pathol 2009, 33(7):1049-57.
• [4]Guimarães GC, Cunha IW, Soares FA, Lopes A, Torres J, Chaux A, et al.: Penile squamous cell carcinoma clinicopathological features, nodal metastasis and outcome in 333 cases. J Urol 2009, 182(2):528-34.
• [5]Zhu Y, Zhang HL, Yao XD, Zhang SL, Dai B, Shen YJ, et al.: Development and evaluation of a nomogram to predict inguinal lymph node metastasis in patients with penile cancer and clinically negative lymph nodes. J Urol 2010, 184(2):539-45.
• [6]Pompeo AC: Extended lymphadenectomy in penile cancer. Can J Urol 2005, 1:30-6. discussion 97–8
• [7]Velazquez EF, Ayala G, Liu H, Chaux A, Zanotti M, Torres J, et al.: Histologic grade and perineural invasion are more important than tumor thickness as predictor of nodal metastasis in penile squamous cell carcinoma invading 5 to 10 mm. Am J Surg Pathol 2008, 32(7):974-9.
• [8]Holley AK, Dhar SK, Xu Y, St Clair DK: Manganese superoxide dismutase: beyond life and death. Amino Acids 2012, 42(1):139-58.
• [9]Johnson F, Giulivi C: Superoxide dismutases and their impact upon human health. Mol Aspects Med 2005, 26(4–5):340-52.
• [10]Kinnula VL, Crapo JD: Superoxide dismutases in malignant cells and human tumors. Free Radic Biol Med 2004, 36(6):718-44.
• [11]Termini L, Filho AL, Maciag PC, Etlinger D, Alves VA, Nonogaki S, et al.: Deregulated expression of superoxide dismutase-2 correlates with different stages of cervical neoplasia. Dis Markers 2011, 30(6):275-81.
• [12]American Joint Committee on Cancer: Penis, in AJCC Cancer Staging Handbook. 7th edition. Springer, New York; 2010.
• [13]Shi SR, Cote RJ, Wu L, Liu C, Datar R, Shi Y, et al.: DNA extraction from archival formalin-fixed, paraffin-embedded tissue sections based on the antigen retrieval principle: heating under the influence of pH. J Histochem Cytochem 2002, 50(8):1005-11.
• [14]Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, et al.: Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985, 230(4732):1350-4.
• [15]de Roda Husman AM, Walboomers JM, van den Brule AJ, Meijer CJ, Snijders PJ: The use of general primers GP5 and GP6 elongated at their 3’ ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol 1995, 76(Pt4):1057-62.
• [16]Ough M, Lewis A, Zhang Y, Hinkhouse MM, Ritchie JM, Oberley LW, et al.: Inhibition of cell growth by overexpression of manganese superoxide dismutase (MnSOD) in human pancreatic carcinoma. Free Radic Res 2004, 38(11):1223-33.
• [17]Toh Y, Kuninaka S, Oshiro T, Ikeda Y, Nakashima H, Baba H, et al.: Overexpression of manganese superoxide dismutase mRNA may correlate with aggressiveness in gastric and colorectal adenocarcinomas. Int J Oncol 2000, 17(1):107-12.
• [18]Janssen AM, Bosman CB, Kruidenier L, Griffioen G, Lamers CB, van Krieken JH, et al.: Superoxide dismutases in the human colorectal cancer sequence. J Cancer Res Clin Oncol 1999, 125(6):327-35.
• [19]Janssen AM, Bosman CB, van Duijn W, Oostendorp-van de Ruit MM, Kubben FJ, Griffioen G, et al.: Superoxide dismutases in gastric and esophageal cancer and the prognostic impact in gastric cancer. Clin Cancer Res 2000, 6(8):3183-92.
• [20]Hwang TS, Choi HK, Han HS: Differential expression of manganese superoxide dismutase, copper/zinc superoxide dismutase, and catalase in gastric adenocarcinomas and normal gastric mucosa. Eur J Surg Oncol 2007, 33(4):474-9.
• [21]Liu X, Wang A, Lo Muzio L, Kolokythas A, Sheng S, Rubini C, et al.: Deregulation of manganese superoxide dismutase (SOD2) expression and lymph node metastasis in tongue squamous cell carcinoma. BMC Cancer 2010, 10:365. BioMed Central Full Text
• [22]Ho JC-m, Zheng S, Comhair SA, Farver C, Erzurum SC: Differential expression of manganese superoxide dismutase and catalase in lung cancer. Cancer Res 2001, 61(23):8578-85.
• [23]Kinnula VL, Crapo JD: Superoxide dismutases in the lung and human lung diseases. Am J Respir Crit Care Med 2003, 167(12):1600-19.
• [24]Svensk AM, Soini Y, Pääkkö P, Hiravikoski P, Kinnula VL: Differential expression of superoxide dismutases in lung cancer. Am J Clin Pathol 2004, 122(3):395-404.
• [25]Haapasalo H, Kyläniemi M, Paunul N, Kinnula VL, Soini Y: Expression of antioxidant enzymes in astrocytic brain tumors. Brain Pathol 2003, 13(2):155-64.
• [26]St Clair D, Zhao Y, Chaiswing L, Oberley T: Modulation of skin tumorigenesis by SOD. Biomed Pharmacother 2005, 59(4):209-14.
• [27]Nelson KK, Ranganathan AC, Mansouri J, Rodriguez AM, Providence KM, Rutter JL, et al.: Elevated SOD2 activity augments matrix metalloproteinase expression: evidence for the involvement of endogenous hydrogen peroxide in regulating metastasis. Clin Cancer Res 2003, 9(1):424-32.
• [28]Das TP, Suman S, Damodaran C: Reactive oxygen species generation inhibits epithelial-mesenchymal transition and promotes growth arrest in prostate cancer cells. Mol Carcinog 2014, 53(7):537-47.
• [29]Kamarajugadda S, Cai Q, Chen H, Nayak S, Zhu J, He M, et al.: Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis. Cell Death Dis 2013, 4:e504.
• [30]Termini L, Boccardo E, Esteves GH, Hirata R Jr, Martins WK, Colo AE, et al.: Characterization of global transcription profile of normal and HPV-immortalized keratinocytes and their response to TNF treatment. BMC Med Genomics 2008, 1:29. BioMed Central Full Text
• [31]Chaux A, Cubilla AL: The role of human papillomavirus infection in the pathogenesis of penile squamous cell carcinomas. Semin Diagn Pathol 2012, 29(2):67-71.
• [32]Anic GM, Giuliano AR: Genital HPV infection and related lesions in men. Prev Med 2011, 53:36-41.
• [33]Pizzocaro G, Algaba F, Horenblas S, Solsona E, Tana S, Van Der Poel H, et al.: EAU penile cancer guidelines 2009. Eur Urol 2010, 57(6):1002-12.
• [34]Lopes A, Hidalgo GS, Kowalski LP, Torloni H, Rossi BM, Fonseca FP: Prognostic factors in carcinoma of the penis: multivariate analysis of 145 patients treated with amputation and lymphadenectomy. J Urol 1996, 156(5):1637-42.
• [35]Ornellas AA, Nóbrega BL, Wei Kin Chin E, Wisnescky A, da Silva PC, de Santos Schwindt AB: Prognostic factors in invasive squamous cell carcinoma of the penis: analysis of 196 patients treated at the Brazilian National Cancer Institute. J Urol 2008, 180(4):1354-9.
• [36]Cubilla AL: The role of pathologic prognostic factors in squamous cell carcinoma of the penis. World J Urol 2009, 27(2):169-77.