Micrometastatic cancer cells in lymph nodes, bone marrow, and blood: Clinical significance and biologic implications

CA Cancer Journal for Clinicians

Volumn 64, Issue 3, 2014, Pages 195-206

  Leong, Stanley P L ^a   Tseng, William W ^b  

^a CALIFORNIA PACIFIC MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

Author keywords

cancer metastasis

Indexed keywords

EOSIN; HEMATOXYLIN; TUMOR MARKER;

ANALYTICAL EQUIPMENT; BLOOD; BONE MARROW; BREAST CANCER; CANCER CELL; CANCER DIAGNOSIS; CANCER STAGING; CIRCULATING TUMOR CELL; CLINICAL TRIAL (TOPIC); DISTANT METASTASIS; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; IMMUNOHISTOCHEMISTRY; LYMPH NODE; LYMPH NODE BIOPSY; LYMPH NODE DISSECTION; MELANOMA; MICROMETASTASIS; NONHUMAN; PERSONALIZED MEDICINE; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; SENTINEL LYMPH NODE; TUMOR GROWTH; TUMOR MICROENVIRONMENT;

CANCER METASTASIS;

BONE MARROW; BREAST NEOPLASMS; HUMANS; LYMPH NODE EXCISION; LYMPHATIC METASTASIS; MELANOMA; NEOPLASM MICROMETASTASIS; NEOPLASTIC CELLS, CIRCULATING; SENTINEL LYMPH NODE BIOPSY;

EID: 84901626284     PISSN: 00079235     EISSN: 15424863     Source Type: Journal    
DOI: 10.3322/caac.21217     Document Type: Review

References (113)

1. Leong SP,. Paradigm of metastasis for melanoma and breast cancer based on the sentinel lymph node experience. Ann Surg Oncol. 2004; 11 (suppl 3): 192S-197S.
2. Leong SP, Cady B, Jablons DM, et al. Clinical patterns of metastasis. Cancer Metastasis Rev. 2006; 25: 221-232.
3. Leong SP, Zuber M, Ferris RL, et al. Impact of nodal status and tumor burden in sentinel lymph nodes on the clinical outcomes of cancer patients. J Surg Oncol. 2011; 103: 518-530.
4. Boland GM, Gershenwald JE,. Sentinel lymph node biopsy in melanoma. Cancer J. 2012; 18: 185-191.
5. Hellman S,. Karnofsky Memorial Lecture. Natural history of small breast cancers. J Clin Oncol. 1994; 12: 2229-2234.
6. Fisher B,. Laboratory and clinical research in breast cancer-a personal adventure: the David A. Karnofsky memorial lecture. Cancer Res. 1980; 40: 3863-3874.
7. Morton DL, Hoon DS, Cochran AJ, et al. Lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: therapeutic utility and implications of nodal microanatomy and molecular staging for improving the accuracy of detection of nodal micrometastases. Ann Surg. 2003; 238: 538-549; discussion 549-550.
8. Martinez-Penuela A, Del Olmo J, Boan JF, Idoate MA,. Incidental findings in negative sentinel lymph nodes of patients with malignant melanoma: report of three cases. Am J Dermatopathol. 2007; 29: 104-105.
9. Itakura E, Huang RR, Wen DR, Cochran AJ,. "Stealth" melanoma cells in histology-negative sentinel lymph nodes. Am J Surg Pathol. 2011; 35: 1657-1665.
10. Carson KF, Wen DR, Li PX, et al. Nodal nevi and cutaneous melanomas. Am J Surg Pathol. 1996; 20: 834-840.
11. Scoggins CR, Ross MI, Reintgen DS, et al. Prospective multi-institutional study of reverse transcriptase polymerase chain reaction for molecular staging of melanoma. J Clin Oncol. 2006; 24: 2849-2857.
12. Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001; 19: 3635-3648.
13. Balch CM, Gershenwald JE, Soong SJ, Thompson JF,. Update on the melanoma staging system: the importance of sentinel node staging and primary tumor mitotic rate. J Surg Oncol. 2011; 104: 379-385.
14. van Akkooi AC, Nowecki ZI, Voit C, et al. Sentinel node tumor burden according to the Rotterdam criteria is the most important prognostic factor for survival in melanoma patients: a multicenter study in 388 patients with positive sentinel nodes. Ann Surg. 2008; 248: 949-955.
15. Wagner JD, Gordon MS, Chuang TY, et al. Predicting sentinel and residual lymph node basin disease after sentinel lymph node biopsy for melanoma. Cancer. 2000; 89: 453-462.
16. Cochran AJ, Wen DR, Huang RR, Wang HJ, Elashoff R, Morton DL,. Prediction of metastatic melanoma in nonsentinel nodes and clinical outcome based on the primary melanoma and the sentinel node. Mod Pathol. 2004; 17: 747-755.
17. Starz H, Balda BR, Kramer KU, Buchels H, Wang H,. A micromorphometry- based concept for routine classification of sentinel lymph node metastases and its clinical relevance for patients with melanoma. Cancer. 2001; 91: 2110-2121.
18. Starz H, Siedlecki K, Balda BR,. Sentinel lymphonodectomy and s-classification: a successful strategy for better prediction and improvement of outcome of melanoma. Ann Surg Oncol. 2004; 11 (suppl 3): 162S-168S.
19. Dewar DJ, Newell B, Green MA, Topping AP, Powell BW, Cook MG,. The microanatomic location of metastatic melanoma in sentinel lymph nodes predicts nonsentinel lymph node involvement. J Clin Oncol. 2004; 22: 3345-3349.
20. van der Ploeg AP, van Akkooi AC, Rutkowski P, et al. Prognosis in patients with sentinel node-positive melanoma is accurately defined by the combined Rotterdam tumor load and Dewar topography criteria. J Clin Oncol. 2011; 29: 2206-2214.
21. Breast. In:, Edge SB, Byrd DR, Compton CC, et al., eds. AJCC Cancer Staging Manual. 7th ed. New York: Springer; 2010: 347-376.
22. Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001; 19: 3622-3634.
23. Leong SP,. Sentinel lymph node mapping and selective lymphadenectomy: the standard of care for melanoma. Curr Treat Options Oncol. 2004; 5: 185-194.
24. Ranieri JM, Wagner JD, Azuaje R, et al. Prognostic importance of lymph node tumor burden in melanoma patients staged by sentinel node biopsy. Ann Surg Oncol. 2002; 9: 975-981.
25. Carlson GW, Murray DR, Lyles RH, Staley CA, Hestley A, Cohen C,. The amount of metastatic melanoma in a sentinel lymph node: does it have prognostic significance? Ann Surg Oncol. 2003; 10: 575-581.
26. Debarbieux S, Duru G, Dalle S, Beatrix O, Balme B, Thomas L,. Sentinel lymph node biopsy in melanoma: a micromorphometric study relating to prognosis and completion lymph node dissection. Br J Dermatol. 2007; 157: 58-67.
27. Scheri RP, Essner R, Turner RR, Ye X, Morton DL,. Isolated tumor cells in the sentinel node affect long-term prognosis of patients with melanoma. Ann Surg Oncol. 2007; 14: 2861-2866.
28. Guggenheim M, Dummer R, Jung FJ, et al. The influence of sentinel lymph node tumour burden on additional lymph node involvement and disease-free survival in cutaneous melanoma-a retrospective analysis of 392 cases. Br J Cancer. 2008; 98: 1922-1928.
29. van der Ploeg IM, Kroon BB, Antonini N, Valdes Olmos RA, Nieweg OE,. Comparison of three micromorphometric pathology classifications of melanoma metastases in the sentinel node. Ann Surg. 2009; 250: 301-304.
30. Francischetto T, Spector N, Neto Rezende JF, et al. Influence of sentinel lymph node tumor burden on survival in melanoma. Ann Surg Oncol. 2010; 17: 1152-1158.
31. Satzger I, Volker B, Meier A, Schenck F, Kapp A, Gutzmer R,. Prognostic significance of isolated HMB45 or Melan A positive cells in melanoma sentinel lymph nodes. Am J Surg Pathol. 2007; 31: 1175-1180.
32. Leong SP, Kashani-Sabet M, Desmond RA, et al. Clinical significance of occult metastatic melanoma in sentinel lymph nodes and other high-risk factors based on long-term follow-up. World J Surg. 2005; 29: 683-691.
33. Reeves ME, Delgado R, Busam KJ, Brady MS, Coit DG,. Prediction of nonsentinel lymph node status in melanoma. Ann Surg Oncol. 2003; 10: 27-31.
34. Lee JH, Essner R, Torisu-Itakura H, Wanek L, Wang H, Morton DL,. Factors predictive of tumor-positive nonsentinel lymph nodes after tumor-positive sentinel lymph node dissection for melanoma. J Clin Oncol. 2004; 22: 3677-3684.
35. Sabel MS, Griffith K, Sondak VK, et al. Predictors of nonsentinel lymph node positivity in patients with a positive sentinel node for melanoma. J Am Coll Surg. 2005; 201: 37-47.
36. Page AJ, Carlson GW, Delman KA, Murray D, Hestley A, Cohen C,. Prediction of nonsentinel lymph node involvement in patients with a positive sentinel lymph node in malignant melanoma. Am Surg. 2007; 73: 674-678; discussion 678-679.
37. Rossi CR, De Salvo GL, Bonandini E, et al. Factors predictive of nonsentinel lymph node involvement and clinical outcome in melanoma patients with metastatic sentinel lymph node. Ann Surg Oncol. 2008; 15: 1202-1210.
38. Baehner FL, Li R, Jenkins T, et al. The impact of primary melanoma thickness and microscopic tumor burden in sentinel lymph nodes on melanoma patient survival. Ann Surg Oncol. 2012; 19: 1034-1042.
39. Balch CM, Gershenwald JE, Soong SJ, et al. Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol. 2010; 28: 2452-2459.
40. Morton DL, Thompson JF, Cochran AJ, et al. MSLT Group. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006; 355: 1307-1317.
41. Morton DL,. Overview and update of the phase III Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT-II) in melanoma. Clin Exp Metastasis. 2012; 29: 699-706.
42. Vuylsteke RJ, Borgstein PJ, van Leeuwen PA, et al. Sentinel lymph node tumor load: an independent predictor of additional lymph node involvement and survival in melanoma. Ann Surg Oncol. 2005; 12: 440-448.
43. van Akkooi AC, de Wilt JH, Verhoef C, et al. Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are these nodes to be considered negative? Ann Oncol. 2006; 17: 1578-1585.
44. Takeuchi H, Morton DL, Kuo C, et al. Prognostic significance of molecular upstaging of paraffin-embedded sentinel lymph nodes in melanoma patients. J Clin Oncol. 2004; 22: 2671-2680.
45. Liu LC, Lang JE, Lu Y, et al. Intraoperative frozen section analysis of sentinel lymph nodes in breast cancer patients: a meta-analysis and single-institution experience. Cancer. 2011; 117: 250-258.
46. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011; 305: 569-575.
47. Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg. 2010; 252: 426-432; discussion 432-433.
48. Viehl CT, Langer I, Guller U, et al. Prognostic impact and therapeutic implications of sentinel lymph node micro-metastases in early-stage breast cancer patients. J Surg Oncol. 2011; 103: 531-533.
49. Dengel LT, Van Zee KJ, King TA, et al. Axillary dissection can be avoided in the majority of clinically node-negative patients undergoing breast-conserving therapy [published online ahead of print August 22, 2013 ]. Ann Surg Oncol.
50. Wang Z, Dong ZY, Chen JQ, Liu JL,. Diagnostic value of sentinel lymph node biopsy in gastric cancer: a meta-analysis. Ann Surg Oncol. 2012; 19: 1541-1550.
51. van der Pas MH, Meijer S, Hoekstra OS, et al. Sentinel-lymph-node procedure in colon and rectal cancer: a systematic review and meta-analysis. Lancet Oncol. 2011; 12: 540-550.
52. van der Zaag ES, Bouma WH, Tanis PJ, Ubbink DT, Bemelman WA, Buskens CJ,. Systematic review of sentinel lymph node mapping procedure in colorectal cancer. Ann Surg Oncol. 2012; 19: 3449-3459.
53. Liptay MJ, D'Amico TA, Nwogu C, et al. Intraoperative sentinel node mapping with technitium-99 in lung cancer: results of CALGB 140203 multicenter phase II trial. J Thorac Oncol. 2009; 4: 198-202.
54. Robison K, Holman LL, Moore RG,. Update on sentinel lymph node evaluation in gynecologic malignancies. Curr Opin Obstet Gynecol. 2011; 23: 8-12.
55. Sadeghi R, Gholami H, Zakavi SR, Kakhki VR, Tabasi KT, Horenblas S,. Accuracy of sentinel lymph node biopsy for inguinal lymph node staging of penile squamous cell carcinoma: systematic review and meta-analysis of the literature. J Urol. 2012; 187: 25-31.
56. Kuriakose MA, Trivedi NP,. Sentinel node biopsy in head and neck squamous cell carcinoma. Curr Opin Otolaryngol Head Neck Surg. 2009; 17: 100-110.
57. Dillman RO, Aaron K, Heinemann FS, McClure SE,. Identification of 12 or more lymph nodes in resected colon cancer specimens as an indicator of quality performance. Cancer. 2009; 115: 1840-1848.
58. Smith DD, Schwarz RR, Schwarz RE,. Impact of total lymph node count on staging and survival after gastrectomy for gastric cancer: data from a large US-population database. J Clin Oncol. 2005; 23: 7114-7124.
59. Yee VS, Thompson JF, McKinnon JG, et al. Outcome in 846 cutaneous melanoma patients from a single center after a negative sentinel node biopsy. Ann Surg Oncol. 2005; 12: 429-439.
60. Zogakis TG, Essner R, Wang HJ, et al. Melanoma recurrence patterns after negative sentinel lymphadenectomy. Arch Surg. 2005; 140: 865-871; discussion 871-872.
61. Chia SK, Speers CH, Bryce CJ, Hayes MM, Olivotto IA,. Ten-year outcomes in a population-based cohort of node-negative, lymphatic, and vascular invasion-negative early breast cancers without adjuvant systemic therapies. J Clin Oncol. 2004; 22: 1630-1637.
62. Schmidt M, Petry IB, Bohm D, et al. Ep-CAM RNA expression predicts metastasis-free survival in three cohorts of untreated node-negative breast cancer. Breast Cancer Res Treat. 2011; 125: 637-646.
63. Siggelkow W, Boehm D, Gebhard S, et al. Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients. BMC Cancer. 2012; 12: 562.
64. Braun S, Vogl FD, Naume B, et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005; 353: 793-802.
65. Leong SP, Nakakura EK, Pollock R, et al. Unique patterns of metastases in common and rare types of malignancy. J Surg Oncol. 2011; 103: 607-614.
66. Collaborative Ocular Melanoma Study Group. Assessment of metastatic disease status at death in 435 patients with large choroidal melanoma in the Collaborative Ocular Melanoma Study (COMS): COMS report no. 15. Arch Ophthalmol. 2001; 119: 670-676.
67. Dieu-Nosjean MC, Antoine M, Danel C, et al. Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J Clin Oncol. 2008; 26: 4410-4417.
68. Coppola D, Nebozhyn M, Khalil F, et al. Unique ectopic lymph node-like structures present in human primary colorectal carcinoma are identified by immune gene array profiling. Am J Pathol. 2011; 179: 37-45.
69. Tseng WW, Demicco EG, Lazar AJ, Lev DC, Pollock RE,. Lymphocyte composition and distribution in inflammatory, well-differentiated retroperitoneal liposarcoma: clues to a potential adaptive immune response and therapeutic implications. Am J Surg Pathol. 2012; 36: 941-944.
70. Messina JL, Fenstermacher DA, Eschrich S, et al. 12-Chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy? Sci Rep. 2012; 2: 765.
71. Gorges TM, Pantel K,. Circulating tumor cells as therapy-related biomarkers in cancer patients. Cancer Immunol Immunother. 2013; 62: 931-939.
72. Hellman S,. Darwin's clinical relevance. Cancer. 1997; 79: 2275-2281.
73. Kim MY, Oskarsson T, Acharyya S, et al. Tumor self-seeding by circulating cancer cells. Cell. 2009; 139: 1315-1326.
74. Lin H, Balic M, Zheng S, Datar R, Cote RJ,. Disseminated and circulating tumor cells: role in effective cancer management. Crit Rev Oncol Hematol. 2011; 77: 1-11.
75. Alix-Panabieres C,. EPISPOT assay: detection of viable DTCs/CTCs in solid tumor patients. Recent Results Cancer Res. 2012; 195: 69-76.
76. Pantel K, Alix-Panabieres C,. Circulating tumour cells in cancer patients: challenges and perspectives. Trends Mol Med. 2010; 16: 398-406.
77. Parkinson DR, Dracopoli N, Petty BG, et al. Considerations in the development of circulating tumor cell technology for clinical use. J Transl Med. 2012; 10: 138.
78. Dong Y, Skelley AM, Merdek KD, et al. Microfluidics and circulating tumor cells. J Mol Diagn. 2013; 15: 149-157.
79. Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004; 351: 781-791.
80. de Bono JS, Scher HI, Montgomery RB, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008; 14: 6302-6309.
81. Cohen SJ, Punt CJ, Iannotti N, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008; 26: 3213-3221.
82. Nagrath S, Sequist LV, Maheswaran S, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007; 450: 1235-1239.
83. Riethdorf S, Wikman H, Pantel K,. Review: biological relevance of disseminated tumor cells in cancer patients. Int J Cancer. 2008; 123: 1991-2006.
84. Janni W, Vogl FD, Wiedswang G, et al. Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse-a European pooled analysis. Clin Cancer Res. 2011; 17: 2967-2976.
85. Berois N, Varangot M, Aizen B, et al. Molecular detection of cancer cells in bone marrow and peripheral blood of patients with operable breast cancer. Comparison of CK19, MUC1 and CEA using RT-PCR. Eur J Cancer. 2000; 36: 717-723.
86. Flatmark K, Borgen E, Nesland JM, et al. Disseminated tumour cells as a prognostic biomarker in colorectal cancer. Br J Cancer. 2011; 104: 1434-1439.
87. Steinert G, Scholch S, Koch M, Weitz J,. Biology and significance of circulating and disseminated tumour cells in colorectal cancer. Langenbecks Arch Surg. 2012; 397: 535-542.
88. Zhang L, Riethdorf S, Wu G, et al. Meta-analysis of the prognostic value of circulating tumor cells in breast cancer. Clin Cancer Res. 2012; 18: 5701-5710.
89. Cristofanilli M, Hayes DF, Budd GT, et al. Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol. 2005; 23: 1420-1430.
90. Bidard FC, Fehm T, Ignatiadis M, et al. Clinical application of circulating tumor cells in breast cancer: overview of the current interventional trials. Cancer Metastasis Rev. 2013; 32: 179-188.
91. Koyanagi K, O'Day SJ, Boasberg P, et al. Serial monitoring of circulating tumor cells predicts outcome of induction biochemotherapy plus maintenance biotherapy for metastatic melanoma. Clin Cancer Res. 2010; 16: 2402-2408.
92. Hayashi N, Yamauchi H,. Role of circulating tumor cells and disseminated tumor cells in primary breast cancer. Breast Cancer. 2012; 19: 110-117.
93. Ignatiadis M, Kallergi G, Ntoulia M, et al. Prognostic value of the molecular detection of circulating tumor cells using a multimarker reverse transcription-PCR assay for cytokeratin 19, mammaglobin A, and HER2 in early breast cancer. Clin Cancer Res. 2008; 14: 2593-2600.
94. Xenidis N, Ignatiadis M, Apostolaki S, et al. Cytokeratin-19 mRNA-positive circulating tumor cells after adjuvant chemotherapy in patients with early breast cancer. J Clin Oncol. 2009; 27: 2177-2184.
95. Peach G, Kim C, Zacharakis E, Purkayastha S, Ziprin P,. Prognostic significance of circulating tumour cells following surgical resection of colorectal cancers: a systematic review. Br J Cancer. 2010; 102: 1327-1334.
96. Rahbari NN, Aigner M, Thorlund K, et al. Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology. 2010; 138: 1714-1726.
97. Hoshimoto S, Faries MB, Morton DL, et al. Assessment of prognostic circulating tumor cells in a phase III trial of adjuvant immunotherapy after complete resection of stage IV melanoma. Ann Surg. 2012; 255: 357-362.
98. Riethdorf S, Muller V, Zhang L, et al. Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res. 2010; 16: 2634-2645.
99. Wulfing P, Borchard J, Buerger H, et al. HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients. Clin Cancer Res. 2006; 12: 1715-1720.
100. Solomayer EF, Becker S, Pergola-Becker G, et al. Comparison of HER2 status between primary tumor and disseminated tumor cells in primary breast cancer patients. Breast Cancer Res Treat. 2006; 98: 179-184.
101. Meng S, Tripathy D, Shete S, et al. HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci U S A. 2004; 101: 9393-9398.
102. Kang Y, Pantel K,. Tumor cell dissemination: emerging biological insights from animal models and cancer patients. Cancer Cell. 2013; 23: 573-581.
103. Joosse SA, Pantel K,. Biologic challenges in the detection of circulating tumor cells. Cancer Res. 2013; 73: 8-11.
104. Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008; 133: 704-715.
105. Yokobori T, Iinuma H, Shimamura T, et al. Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis. Cancer Res. 2013; 73: 2059-2069.
106. Yu M, Bardia A, Wittner BS, et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science. 2013; 339: 580-584.
107. Amerasekera S, Turner M, Purushotham AD,. Paget's "seed and soil" hypothesis revisited. J BUON. 2004; 9: 465-467.
108. Goss PE, Chambers AF,. Does tumour dormancy offer a therapeutic target? Nat Rev Cancer. 2010; 10: 871-877.
109. Uhr JW, Pantel K., Controversies in clinical cancer dormancy. Proc Natl Acad Sci U S A. 2011; 108: 12396-12400.
110. Tseng WW, Fadaki N, Leong SP,. Metastatic tumor dormancy in cutaneous melanoma: does surgery induce escape? Cancers (Basel). 2011; 3: 730-746.
111. Kaplan RN, Riba RD, Zacharoulis S, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005; 438: 820-827.
112. Peinado H, Lavotshkin S, Lyden D,. The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts. Semin Cancer Biol. 2011; 21: 139-146.
113. Zoccoli A, Iuliani M, Pantano F, et al. Premetastatic niche: ready for new therapeutic interventions? Expert Opin Ther Targets. 2012; 16 (suppl 2): S119-S129.