期刊论文详细信息
Journal for ImmunoTherapy of Cancer
Programmed death ligand-1 expression in adrenocortical carcinoma: an exploratory biomarker study
Toni K Choueiri5  Aymen Elfiky5  Gordon J Freeman5  F Stephen Hodi2  Joaquim Bellmunt5  Carlos E Poli-de-Figueiredo3  Marina D Kaymakcalan6  Megan E Lampron6  Ingrid Carvo4  Jiaxi Song4  Rana R McKay5  Gabriela H Telό1  Marcella Callea4  Sabina Signoretti5  André P Fay3 
[1]Joslin Diabetes Center, One Joslin Place, Boston 02215, MA, USA
[2]Center of Immuno-Oncology, 450 Brookline Avenue, Boston 02215, MA, USA
[3]Programa de Pós-Graduação em Medicina e Ciências da Saúde, Faculdade de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga 6690, Porto Alegre 90619-900, RS, Brazil
[4]Brigham and Women’s Hospital, 75 Francis Street (Thorn Building 504A), Boston 02215, MA, USA
[5]Harvard Medical School, 25 Shattuck Street, Boston 02115, MA, USA
[6]Dana-Farber Cancer Institute, 450 Brookline Avenue (DANA 1230), Boston 02215, MA, USA
关键词: Immunotherapy;    PD-1 inhibitors;    PD-L1;    Adrenocortical carcinoma;   
Others  :  1139865
DOI  :  10.1186/s40425-015-0047-3
 received in 2014-11-14, accepted in 2015-01-17,  发布年份 2015
PDF
【 摘 要 】

Background

Adrenocortical carcinoma (ACC) is a rare tumor in which prognostic factors are still not well established. Programmed Death Ligand-1 (PD-L1) expression in ACC and its association with clinico-pathological features and survival outcomes are unknown.

Methods

Formalin-fixed paraffin-embedded (FFPE) specimens were obtained from 28 patients with ACC. PD-L1 expression was evaluated by immunohistochemistry (IHC) in both tumor cell membrane and tumor infiltrating mononuclear cells (TIMC). PD-L1 positivity on tumor cells was defined as ≥5% tumor cell membrane staining. TIMC were evaluated by IHC using a CD45 monoclonal antibody. For PD-L1 expression in TIMC, a combined score based on the extent of infiltrates and percentage of positive cells was developed. Any score greater that zero was considered PD-L1 positive. Baseline clinico-pathological characteristics and follow up data were retrospectively collected. Comparisons between PD-L1 expression and clinico-pathological features were evaluated using unpaired t-test and Fisher’s exact test. Kaplan-Meier method and log-rank test were used to assess association between PD-L1 expression and 5-year overall survival (OS).

Results

Among 28 patients with surgically treated ACC, 3 (10.7%) were considered PD-L1 positive on tumor cell membrane. On the other hand, PD-L1 expression in TIMC was performed in 27 specimens and PD-L1 positive staining was observed in 19 (70.4%) patients. PD-L1 positivity in either tumor cell membrane or TIMC was not significantly associated with higher stage at diagnosis, higher tumor grade, excessive hormone secretion, or OS.

Conclusions

PD-L1 expression can exist in ACC in both tumor cell membrane and TIMC with no relationship to clinico-pathologic parameters or survival.

【 授权许可】

   
2015 Fay et al.; licensee BioMed Central.

【 预 览 】
附件列表
Files Size Format View
20150323095925851.pdf 1167KB PDF download
Figure 2. 19KB Image download
Figure 1. 83KB Image download
【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】
  • [1]Third national cancer survey: incidence data. Natl Cancer Inst Monogr. 1975;41:i-x, 1–454.
  • [2]Kebebew E, Reiff E, Duh QY, Clark OH, McMillan A: Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress? World J Surg 2006, 30(5):872-8. doi:10.1007/s00268-005-0329-x
  • [3]Bilimoria KY, Shen WT, Elaraj D, Bentrem DJ, Winchester DJ, Kebebew E, et al.: Adrenocortical carcinoma in the United States: treatment utilization and prognostic factors. Cancer 2008, 113(11):3130-6. doi:10.1002/cncr.23886
  • [4]Khorram-Manesh A, Ahlman H, Jansson S, Wangberg B, Nilsson O, Jakobsson CE, et al.: Adrenocortical carcinoma: surgery and mitotane for treatment and steroid profiles for follow-up. World J Surg 1998, 22(6):605-11. discussion 11–2
  • [5]Luton JP, Cerdas S, Billaud L, Thomas G, Guilhaume B, Bertagna X, et al.: Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med 1990, 322(17):1195-201. doi:10.1056/NEJM199004263221705
  • [6]op den Winkel J, Pfannschmidt J, Muley T, Grunewald C, Dienemann H, Fassnacht M, et al.: Metastatic adrenocortical carcinoma: results of 56 pulmonary metastasectomies in 24 patients. Ann Thorac Surg 2011, 92(6):1965-70. doi:10.1016/j.athoracsur.2011.07.088
  • [7]Fay AP, Elfiky A, Telo GH, McKay RR, Kaymakcalan M, Nguyen PL, et al. Adrenocortical carcinoma: the management of metastatic disease. Crit Rev Oncol Hematol. 2014. doi:10.1016/j.critrevonc.2014.05.009.
  • [8]Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, et al.: Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med 2012, 366(23):2189-97. doi:10.1056/NEJMoa1200966
  • [9]Berruti A, Terzolo M, Pia A, Angeli A, Dogliotti L: Mitotane associated with etoposide, doxorubicin, and cisplatin in the treatment of advanced adrenocortical carcinoma. Italian Group for the study of adrenal cancer. Cancer 1998, 83(10):2194-200.
  • [10]Khan TS, Imam H, Juhlin C, Skogseid B, Grondal S, Tibblin S, et al.: Streptozocin and o, p’DDD in the treatment of adrenocortical cancer patients: long-term survival in its adjuvant use. Ann Oncol 2000, 11(10):1281-7.
  • [11]Sperone P, Ferrero A, Daffara F, Priola A, Zaggia B, Volante M, et al.: Gemcitabine plus metronomic 5-fluorouracil or capecitabine as a second-/third-line chemotherapy in advanced adrenocortical carcinoma: a multicenter phase II study. Endocr Relat Cancer 2010, 17(2):445-53. doi:10.1677/ERC-09-0281
  • [12]Barlaskar FM, Spalding AC, Heaton JH, Kuick R, Kim AC, Thomas DG, et al.: Preclinical targeting of the type I insulin-like growth factor receptor in adrenocortical carcinoma. J Clin Endocrinol Metab 2009, 94(1):204-12. doi:10.1210/jc.2008-1456
  • [13]De Martino MC, van Koetsveld PM, Feelders RA, Sprij-Mooij D, Waaijers M, Lamberts SW, et al.: The role of mTOR inhibitors in the inhibition of growth and cortisol secretion in human adrenocortical carcinoma cells. Endocr Relat Cancer 2012, 19(3):351-64. doi:10.1530/ERC-11-0270
  • [14]Carden ESK CP, Jones RL, Alam SM, Johnson FM, Stephens AW, Poondru S, et al.: Phase I study of intermittent dosing of OSI-906, a dual tyrosine kinase inhibitor of insulin-like growth factor-1 receptor (IGF- 1R) and insulin receptor (IR) in patients with advanced solid tumors. J Clin Oncol 2010, 28:15s. 2010 (suppl; abstr 2530)
  • [15]Kroiss M, Quinkler M, Johanssen S, van Erp NP, Lankheet N, Pollinger A, et al.: Sunitinib in refractory adrenocortical carcinoma: a phase II, single-arm, open-label trial. J Clin Endocrinol Metab 2012, 97(10):3495-503. doi:10.1210/jc.2012-1419
  • [16]Jimenez P, Guix M, Milagro NL, Mateos LL, Mendez Vidal MJ, Climent Duran MA, et al. Phase II study of dovitinib in first-line metastatic or nonresectable primary adrenocortical carcinoma (ACC): SOGUG study 2011–03. J Clin Oncol. 2012;30(suppl; abstr TPS4688):2014.
  • [17]O’Sullivan C, Edgerly M, Velarde M, Wilkerson J, Venkatesan AM, Pittaluga S, et al.: The VEGF inhibitor axitinib has limited effectiveness as a therapy for adrenocortical cancer. J Clin Endocrinol Metab 2014, 99(4):1291-7. doi:10.1210/jc.2013-2298
  • [18]Lerario AM, Worden FP, Ramm CA, Hasseltine EA, Stadler WM, Else T, et al.: The combination of insulin-like growth factor receptor 1 (IGF1R) antibody cixutumumab and mitotane as a first-line therapy for patients with recurrent/metastatic adrenocortical carcinoma: a multi-institutional NCI-sponsored trial. Hormones Cancer 2014, 5(4):232-9. doi:10.1007/s12672-014-0182-1
  • [19]Francisco LM, Sage PT, Sharpe AH: The PD-1 pathway in tolerance and autoimmunity. Immunol Rev 2010, 236:219-42. doi:10.1111/j.1600-065X.2010.00923.x
  • [20]McDermott DF, Atkins MB: PD-1 as a potential target in cancer therapy. Cancer Med 2013, 2(5):662-73. doi:10.1002/cam4.106
  • [21]Thompson RH, Dong H, Kwon ED: Implications of B7-H1 expression in clear cell carcinoma of the kidney for prognostication and therapy. Clin Cancer Res 2007, 13(2 Pt 2):709s-15. doi:10.1158/1078-0432.CCR-06-1868
  • [22]Ohigashi Y, Sho M, Yamada Y, Tsurui Y, Hamada K, Ikeda N, et al.: Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res 2005, 11(8):2947-53. doi:10.1158/1078-0432.CCR-04-1469
  • [23]Lughezzani G, Sun M, Perrotte P, Jeldres C, Alasker A, Isbarn H, et al.: The European Network for the study of adrenal tumors staging system is prognostically superior to the international union against cancer-staging system: a North American validation. Eur J Cancer 2010, 46(4):713-9. doi:10.1016/j.ejca.2009.12.007
  • [24]Thompson RH, Kwon ED: Significance of B7-H1 overexpression in kidney cancer. Clin Genitourin Cancer 2006, 5(3):206-11. doi:10.3816/CGC.2006.n.038
  • [25]Thompson RH, Gillett MD, Cheville JC, Lohse CM, Dong H, Webster WS, et al.: Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci U S A 2004, 101(49):17174-9. doi:10.1073/pnas.0406351101
  • [26]Boland JM, Kwon ED, Harrington SM, Wampfler JA, Tang H, Yang P, et al.: Tumor B7-H1 and B7-H3 expression in squamous cell carcinoma of the lung. Clin Lung Cancer 2013, 14(2):157-63. doi:10.1016/j.cllc.2012.05.006
  • [27]Mullane SA, Werner L, Callea M, Fay AP, Leow JJ, Choueiri TK, et al.: PD-L1 expression in mononuclear cells and not in tumor cells, correlated with prognosis in metastatic urothelial carcinoma. J Clin Oncol 2014, 32(suppl; abstr 4552):5s.
  • [28]Harshman LC, Choueiri TK, Drake C, Stephen Hodi F Jr: Subverting the B7-H1/PD-1 pathway in advanced melanoma and kidney cancer. Cancer J 2014, 20(4):272-80. doi:10.1097/PPO.0000000000000055
  • [29]Karakousis CP, Rao U, Moore R: Adrenal adenocarcinomas: histologic grading and survival. J Surg Oncol 1985, 29(2):105-11.
  • [30]Hogan TF, Gilchrist KW, Westring DW, Citrin DL: A clinical and pathological study of adrenocortical carcinoma: therapeutic implications. Cancer 1980, 45(11):2880-3.
  • [31]Assie G, Antoni G, Tissier F, Caillou B, Abiven G, Gicquel C, et al.: Prognostic parameters of metastatic adrenocortical carcinoma. J Clin Endocrinol Metab 2007, 92(1):148-54. doi:10.1210/jc.2006-0706
  • [32]Mantovani A, Romero P, Palucka AK, Marincola FM: Tumour immunity: effector response to tumour and role of the microenvironment. Lancet 2008, 371(9614):771-83. doi:10.1016/S0140-6736(08)60241-X
  • [33]Willenberg HS, Stratakis CA, Marx C, Ehrhart-Bornstein M, Chrousos GP, Bornstein SR: Aberrant interleukin-1 receptors in a cortisol-secreting adrenal adenoma causing cushing’s syndrome. N Engl J Med 1998, 339(1):27-31. doi:10.1056/NEJM199807023390105
  • [34]Quezada SA, Peggs KS: Exploiting CTLA-4, PD-1 and PD-L1 to reactivate the host immune response against cancer. Br J Cancer 2013, 108(8):1560-5. doi:10.1038/bjc.2013.117
  • [35]Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al.: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012, 366(26):2443-54. doi:10.1056/NEJMoa1200690
  • [36]DC Cho, JA Sosman, M Sznol, MS Gordon, A Hollebecque, O Hamid, et al. Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with metastatic renal cell carcinoma (mRCC). ASCO Annual Meeting. J Clin Oncol. 2013;31(suppl; abstr 4505).
  • [37]Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, et al.: Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013, 369(2):122-33. doi:10.1056/NEJMoa1302369
  • [38]Bellmunt J, Powles T, Braiteh F, Vogelzang N, Cruz C, Burris H, et al.: Inhibition of PD-L1 by MPDL3280A leads to clinical activity in pts with metastatic urothelial bladder cancer (UBC). Ann Oncol 2014, 25(suppl_4):iv280-304. doi:101093/annonc/mdu337
  • [39]Choueiri TK, Fishman MN, Escudier B, Kim JJ, Kluger H, Stadler WM, et al.: Immunomodulatory activity of nivolumab in previously treated and untreated metastatic renal cell carcinoma (mRCC): biomarker-based results from a randomized clinical trial. J Clin Oncol 2014, 32(suppl; abstr 5012):5s.
  • [40]Choueiri TK. Highlights of the Day III Session - Genitourinary (Nonprostate) Cancer 2014
  • [41]Green MR, Monti S, Rodig SJ, Juszczynski P, Currie T, O’Donnell E, et al.: Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood 2010, 116(17):3268-77. doi:10.1182/blood-2010-05-282780
  • [42]Hsieh C, Chang A, Brandt D, Guttikonda R, Utset TO, Clark MR: Predicting outcomes of lupus nephritis with tubulointerstitial inflammation and scarring. Arthritis Care Res 2011, 63(6):865-74. doi:10.1002/acr.20441
  • [43]Haley KJ, Sunday ME, Wiggs BR, Kozakewich HP, Reilly JJ, Mentzer SJ, et al.: Inflammatory cell distribution within and along asthmatic airways. Am J Respir Crit Care Med 1998, 158(2):565-72. doi:10.1164/ajrccm.158.2.9705036
  • [44]Choueiri TK, Fay AP, Gray KP, Callea M, Ho TH, Albiges L, et al.: PD-L1 expression in nonclear-cell renal cell carcinoma. Ann Oncol 2014, 25(11):2178-84. doi:10.1093/annonc/mdu445
  文献评价指标  
  下载次数:0次 浏览次数:9次