Abstract
Flow cytometry has been validated as an objective method of demonstrating and quantifying micrometastases. Micrometastases within bone marrow indicate a poor prognosis in patients with upper gastrointestinal, colorectal and breast epithelial tumours. We prospectively sought to assess the feasibility of testing rib marrow for bone marrow micrometastases in head and neck cancer and to report their frequency in a cohort of patients. Nine patients were enrolled in the study. Bone marrow was obtained before manipulation of the primary tumour. Micrometastatic cells were detected by staining contaminant cytokeratin-18 positive cells and using the twin techniques of immuncytochemistry and flow cytometry. Cellular marrow was retrieved in 100% of cases. Micrometastases were detected in one out of nine epithelial tumours on both flow cytometry and immunocytochemistry. The detection rate appeared to be independent of TN staging. We were unable to culture the cells. Preoperative detection of bone marrow micrometastases may reflect transient shedding of cells, metastatic potential or residual disease. This prospective study confirms the feasibility of using rib marrow in future studies investigating micrometastases in head and neck cancer.
Similar content being viewed by others
References
Ambrosch P, Kron M, Fischer G, Brinck U (1995) Micrometastases in carcinoma of the upper aerodigestive tract: detection, risk of metastasizing and prognostic value of depth of invasion. Head Neck 17:473–479
Braun S, Pantel K, Muller P et al (2000) Cytokeratin-positive cells in the bone marrow and survival of patients with stage 1, 11 or 111 breast cancer. N Engl J Med 342:525–533
Brugger W, Bross KJ, Glatt M, Weber F, Mertelsmann R, Kanz L (1994) Mobilization of tumor cells and hemapoietic progenitor cells into peripheral blood of patients with solid tumors. Blood 83:636–640
Collins JK, O’Mahony A, O’Brien F, Corbett A, Morrissey D, O’Donoghue M, O’Sullivan G (1992) Evaluation of newly established cell lines as models to study growth, invasion and metastatic spread in oesophageal cancer. Fibrinolysis 6 [Suppl 4]:83–88
Cordell JL, Falini B, Erber WN, Gosh AK, Abdulaziz Z, Mac Donald S, Pulford KA, Stein H, Mason DY (1984) Immunoenzymatic labelling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal antialkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229
Cote RJ, Beattie EJ, Chaiwun B, Shi S-R, Harvey J, Chen S-C, Sherrod AE, Groshen S, Taylor CR (1995) Detection of occult bone marrow micrometastases in patients with operable lung carcinoma. Ann Surg 222:415–425
Cote RJ, Rosen PP, Lesser ML, Old LJ, Osborne MP (1991) Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases. J Clin Oncol 9:1749–1756
Foulds L (1964) The experimental study of tumour progression. Cancer Res 14:327
Funke I, Schraut W (1998) Met-analyses of studies on bone marrow micrometastases: an independent prognostic impact remains to be substantiated. J Clin Oncol 16:557–566
Gath HJ, Heissler E, Hell B, Bier J, Riethmuller G, Pantel K (1995) Immunocytologic detection of isolated tumor cells in bone marrow of patients with squamous cell carcinomas of the head and neck region. Int J Oral Maxillofac Surg 24:351–355
Jendraschak E, Sage EH (1996) Regulation of angiogenesis by SPARC and angiostatin: implications for tumour cell biology. Semin Cancer Biol 7:139–146
Juhl H, Stritzel M, Wroblewski A, Henne-Bruns D, Kremer B, Schmiegel W, Neumaier M, Wagener C, Schreiber HW, Kalthoff H (1994) Immunocytological detection of micrometastatic cells: comparative evaluation of findings in the peritoneal cavity and the bone marrow of gastric, colorectal and pancreatic cancer patients. Int J Cancer 57:330–335
Lindemann F, Schlimok G, Dirschedl P, Witte J, Riethmüller G (1992) Prognostic significance of micrometastatic tumour cells in bone marrow of colorectal cancer patients. Lancet 340:685–690
Mansi JL, Berger U, Easton D, McDonnell T, Redding WH, Gazet J-C, McKinna A, Powles TJ, Coombes RC (1987) Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases. BMJ (Clin Res Ed) 295:1093–1096
Nishizaki T, Matsumata T, Kanematsu T (1990) Surgical manipulation of VX2 carcinoma in the rabbit liver evokes enhancement of metastasis. J Surg Res 49:92–97
Nossal GJV (1994) Minimal residual disease as the target for immunotherapy of cancer. Lancet 343:1172–1174
O’Sullivan GC, Collins JK, O’Brien F, Crowley B, Murphy K, Lee G, Shanahan F (1995) Micrometastases in bone marrow of patients undergoing “curative” surgery for gastrointestinal cancer. Gastroenterology 109:1535–1540
O’Sullivan GC, Collins JK, Kelly J, Morgan J, Madden M, Shanahan F (1997) Micrometastases: marker of metastatic potential or evidence of residual disease? Gut 40:512–515
O’Sullivan GC, Sheehan D, Clarke A, Stuart R, Kelly J, Kiely MD, Walsh T, Collins JK, Shanahan F (1999) Micrometastases in esophagogastric cancer: high detection rate in resected rib segments. Gastroenterology 116:543–548
Pantel K, Izbicki J, Passlick B, Angstwurm M, Häussinger K, Thetter O, Riethmüller G (1996) Frequency and prognostic significance of isolated tumour cells in bone marrow of patients with non-small-cell lung cancer without overt metastases. Lancet 347:649–653
Relihan N, McGreal G, Kelly J, Ryan D, O’Sullivan GC, Redmond HP (1999) Combined sentinel lymph-node mapping and bone-marrow micrometastatic analysis for improved staging in breast cancer. Lancet 354:129–130
Riethmüller G, Schneider-Gädicke E, Schlimok G, Schmiegel W, Raab R, Hoffken K, Gruber R, Pichlmaier H, Hirche H (1994) Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes’ C colorectal carcinoma. Lancet 343:1177–1183
Schlimok G, Funke I, Holzmann B, Göttlinger G, Schmidt G, Häuser H, Swierkot S, Warnecke HH, Schneider B, Koprowski H (1987) Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in-vivo labeling with anti-17–1A monoclonal antibodies. Proc Natl Acad Sci (USA) 84:8672–8676
Schlimok G, Riethmüller G (1990) Detection, characterization and tumourigenicity of disseminated tumor cells in human bone marrow. Semin Cancer Biol 1:207–215
Shpall EJ, Jones RB (1994) Release of tumor cells from bone marrow. Blood 83:623–625
van den Brekel MW, van der Waal I, Meijer CJ, Freeman JL, Castelijns JA, Snow GB (1996) The incidence of micrometastases in neck dissection specimens obtained from elective neck dissections. Laryngoscope 106:987–991
Wollenberg B, Ollesch A, Maag K, Funke I, Wilmes E (1994) Micrometastases in bone marrow of patients with cancers in the head and neck area. Laryngorhinootologie 73:88–93
Woolgar JA (1997) Detailed topography of cervical lymph-note metastases from oral squamous cell carcinoma. Int J Oral Maxillofac Surg 26:3–9
Woolgar JA (1999) Micrometastasis in oral/oropharyngeal squamous cell carcinoma: incidence, histopathological features and clinical implications. Br J Oral Maxillofac Surg 37:181–186
Author information
Authors and Affiliations
Corresponding author
Additional information
This paper was presented at the ORS meeting, Spring Session, Hull, United Kingdom, April 2001.
Rights and permissions
About this article
Cite this article
Skinner, L.J., Conlon, B.J., Russell, J.D. et al. Detection of bone marrow micrometastases in the rib marrow of head and neck cancer patients: a prospective pilot study. Eur Arch Otorhinolaryngol 262, 103–106 (2005). https://doi.org/10.1007/s00405-004-0752-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00405-004-0752-x