Abstract
Background
Currently, tumor-node-metastasis stage and histologic type are the established prognostic factors for malignant pleural mesothelioma, whereas no prognostic markers have been established for clinical practice. We investigated the prognostic value of CD10, a metalloproteinase that can promote cancer aggressiveness through enzymatic degradation and intracellular signaling crosstalk, in malignant pleural mesothelioma.
Methods
CD10 immunostaining was performed for 176 cases of malignant pleural mesothelioma (epithelioid, 148; biphasic, 14; sarcomatoid, 14), and its expression was dichotomized as negative (no staining) or positive (any staining). Epithelioid tumors were classified as pleomorphic subtype when cytologic pleomorphism was ≥10 % of the tumor. Overall survival (OS) was analyzed by log-rank tests and Cox proportional hazard models.
Results
Tumoral CD10 expression was identified in 42 % of epithelioid non-pleomorphic tumors, 57 % of epithelioid pleomorphic tumors, 79 % of biphasic tumors, and 93 % of sarcomatoid tumors (p < 0.001). Positive CD10 expression was correlated with higher mitotic count (p = 0.002). Overall survival for patients with positive CD10 expression was significantly shorter than that for patients with negative CD10 expression in all patients (p = 0.001) and in patients with epithelioid tumor (p = 0.04). On multivariate analysis, CD10 expression was an independent prognostic factor for all patients (hazard ratio 1.48; p = 0.019).
Conclusions
Tumoral CD10 expression correlated with aggressive histologic types and higher mitotic activity and is an independent prognostic factor for patients with malignant pleural mesothelioma.
Similar content being viewed by others
References
Flores RM, Zakowski M, Venkatraman E, et al. Prognostic factors in the treatment of malignant pleural mesothelioma at a large tertiary referral center. J Thorac Oncol. 2007;2(10):957–965.
Rusch VW, Giroux D, Kennedy C, et al. Initial analysis of the International Association For the Study of Lung Cancer mesothelioma database. J Thorac Oncol. 2012;7(11):1631–1639.
Sugarbaker DJ, Flores RM, Jaklitsch MT, et al. Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg. 1999;117(1):54–63; discussion 63–55.
Kadota K, Suzuki K, Colovos C, et al. A nuclear grading system is a strong predictor of survival in epithelioid diffuse malignant pleural mesothelioma. Mod Pathol. 2012;25(2):260–271.
Kadota K, Suzuki K, Sima CS, Rusch VW, Adusumilli PS, Travis WD. Pleomorphic epithelioid diffuse malignant pleural mesothelioma: a clinicopathological review and conceptual proposal to reclassify as biphasic or sarcomatoid mesothelioma. J Thorac Oncol. 2011;6(5):896–904.
Righi L, Papotti MG, Ceppi P, et al. Thymidylate synthase but not excision repair cross-complementation group 1 tumor expression predicts outcome in patients with malignant pleural mesothelioma treated with pemetrexed-based chemotherapy. J Clin Oncol. 2010;28(9):1534–1539.
Burt BM, Bader A, Winter D, Rodig SJ, Bueno R, Sugarbaker DJ. Expression of interleukin-4 receptor alpha in human pleural mesothelioma is associated with poor survival and promotion of tumor inflammation. Clin Cancer Res. 2012;18(6):1568–1577.
Suzuki K, Kadota K, Sima CS, et al. Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients. Cancer Immunol Immunother. 2011;60(12):1721–1728.
Kadota K, Kachala SS, Nitadori J, et al. High SUVmax on FDG-PET indicates pleomorphic subtype in epithelioid malignant pleural mesothelioma: supportive evidence to reclassify pleomorphic as nonepithelioid histology. J Thorac Oncol. 2012;7(7):1192–1197.
McIntosh GG, Lodge AJ, Watson P, et al. NCL-CD10-270: a new monoclonal antibody recognizing CD10 in paraffin-embedded tissue. Am J Pathol. 1999;154(1):77–82.
Shipp MA, Look AT. Hematopoietic differentiation antigens that are membrane-associated enzymes: cutting is the key! Blood. 1993;82(4):1052–1070.
Turner AJ, Tanzawa K. Mammalian membrane metallopeptidases: NEP, ECE, KELL, and PEX. FASEB J. 1997;11(5):355–364.
Iwaya K, Ogawa H, Izumi M, Kuroda M, Mukai K. Stromal expression of CD10 in invasive breast carcinoma: a new predictor of clinical outcome. Virchows Arch. 2002;440(6):589–593.
Kim HS, Kim GY, Kim YW, Park YK, Song JY, Lim SJ. Stromal CD10 expression and relationship to the E-cadherin/beta-catenin complex in breast carcinoma. Histopathology. 2010;56(6):708–719.
Desmedt C, Majjaj S, Kheddoumi N, et al. Characterization and clinical evaluation of CD10 + stroma cells in the breast cancer microenvironment. Clin Cancer Res. 2012;18(4):1004–1014.
Fujimoto Y, Nakanishi Y, Sekine S, et al. CD10 expression in colorectal carcinoma correlates with liver metastasis. Dis Colon Rectum. 2005;48(10):1883–1889.
Kuniyasu H, Luo Y, Fujii K, et al. CD10 enhances metastasis of colorectal cancer by abrogating the anti-tumoural effect of methionine-enkephalin in the liver. Gut. 2010;59(3):348–356.
Khanh do T, Mekata E, Mukaisho K, et al. Prognostic role of CD10(+) myeloid cells in association with tumor budding at the invasion front of colorectal cancer. Cancer Sci. 2011;102(9):1724–1733.
Dall’Era MA, True LD, Siegel AF, Porter MP, Sherertz TM, Liu AY. Differential expression of CD10 in prostate cancer and its clinical implication. BMC Urol. 2007;7(1):3.
Fleischmann A, Rocha C, Saxer-Sekulic N, Zlobec I, Sauter G, Thalmann GN. High CD10 expression in lymph node metastases from surgically treated prostate cancer independently predicts early death. Virchows Arch. 2011;458(6):741–748.
Ho ME, Quek SI, True LD, et al. Prostate cancer cell phenotypes based on AGR2 and CD10 expression. Mod Pathol. 2013;26(6):849–859.
Biasoli I, Morais JC, Scheliga A, et al. CD10 and Bcl-2 expression combined with the International Prognostic Index can identify subgroups of patients with diffuse large-cell lymphoma with very good or very poor prognoses. Histopathology. 2005;46(3):328–333.
Bilalovic N, Blystad AK, Golouh R, et al. Expression of bcl-6 and CD10 protein is associated with longer overall survival and time to treatment failure in follicular lymphoma. Am J Clin Pathol. 2004;121(1):34–42.
Butnor KJ, Nicholson AG, Allred DC, et al. Expression of renal cell carcinoma-associated markers erythropoietin, CD10, and renal cell carcinoma marker in diffuse malignant mesothelioma and metastatic renal cell carcinoma. Arch Pathol Lab Med. 2006;130(6):823–827.
Greene F, Page D, Fleming I, et al. AJCC cancer staging manual. 6th ed. New York: Springer; 2002.
Kadota K, Suzuki K, Kachala SS, et al. A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma. Mod Pathol. 2012;25(8):1117–1127.
Yoshizawa A, Fukuoka J, Shimizu S, et al. Overexpression of phospho-eIF4E is associated with survival through AKT pathway in non-small cell lung cancer. Clin Cancer Res. 2010;16(1):240–248.
Suzuki K, Kadota K, Sima CS, et al. Clinical impact of immune microenvironment in stage I lung adenocarcinoma: tumor interleukin-12 receptor beta2 (IL-12Rbeta2), IL-7R, and stromal FoxP3/CD3 ratio are independent predictors of recurrence. J Clin Oncol. 2013;31(4):490–498.
Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21(14):2636–2644.
Krug LM, Pass HI, Rusch VW, et al. Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. J Clin Oncol. 2009;27(18):3007–3013.
Fukusumi T, Ishii H, Konno M, et al. CD10 as a novel marker of therapeutic resistance and cancer stem cells in head and neck squamous cell carcinoma. Br J Cancer. 2014;111(3):506–514.
Ravel D, Dubois V, Quinonero J, et al. Preclinical toxicity, toxicokinetics, and antitumoral efficacy studies of DTS-201, a tumor-selective peptidic prodrug of doxorubicin. Clin Cancer Res. 2008;14(4):1258–1265.
Pan C, Cardarelli PM, Nieder MH, et al. CD10 is a key enzyme involved in the activation of tumor-activated peptide prodrug CPI-0004Na and novel analogues: implications for the design of novel peptide prodrugs for the therapy of CD10(+) tumors. Cancer Res. 2003;63(17):5526–5531.
Scherpereel A, Berghmans T, Lafitte JJ, et al. Valproate-doxorubicin: promising therapy for progressing mesothelioma: a phase II study. Eur Respir J. 2011;37(1):129–135.
Arrieta O, Medina LA, Estrada-Lobato E, et al. First-line chemotherapy with liposomal doxorubicin plus cisplatin for patients with advanced malignant pleural mesothelioma: phase II trial. Br J Cancer. 2012;106(6):1027–1032.
Acknowledgment
The authors’ laboratory work is supported in part by Grants from the National Institutes of Health (R21 CA164568-01A1, R21 CA164585-01A1, R01 CA136705-06, U54 CA137788, P30 CA008748, and P50 CA086438-13), the US Department of Defense (PR101053 and LC110202), Mr. William H. Goodwin and Mrs. Alice Goodwin, the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center. We thank Joe Dycoco of the Memorial Sloan Kettering Thoracic Surgery Service for assisting with the Thoracic Surgery Service’s malignant pleural mesothelioma database; Irina Linkov, Avani Giri, and Louie Lopez of the Memorial Sloan Kettering Pathology Core Facility for their help in making the tissue microarray and for technical assistance with immunohistochemistry; and David Sewell and Alex Torres of the Memorial Sloan Kettering Thoracic Surgery Service for their editorial assistance.
Disclosure
Kyuichi Kadota, Jonathan Villena-Vargas, Jun-ichi Nitadori, Camelia S. Sima, David R. Jones, William D. Travis, and Prasad S. Adusumilli do not have any commercial interests to disclose.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kadota, K., Villena-Vargas, J., Nitadori, Ji. et al. Tumoral CD10 Expression Correlates with Aggressive Histology and Prognosis in Patients with Malignant Pleural Mesothelioma. Ann Surg Oncol 22, 3136–3143 (2015). https://doi.org/10.1245/s10434-015-4374-x
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-015-4374-x