This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Partridge, M. Articles by Langdon, J. D. Search for Related Content PubMed PubMed Citation Articles by Partridge, M. Articles by Langdon, J. D.

Detection of Minimal Residual Cancer to Investigate Why Oral Tumors Recur Despite Seemingly Adequate Treatment

Maxillofacial Unit/Oncology, King’s College Hospital, London SE5 8RX, United Kingdom

Improvements in surgery and radiotherapy techniques have led to only a modest increase in the 5-year survival rate for patients with head and neck cancer. This is because the pattern of clinical disease is changing, such that locoregional recurrence now accounts for fewer treatment failures, but more patients develop a second primary cancer or distant metastatic disease. In this study, we have used the p53 phage plaque assay, immunocytochemistry, and mutational analysis to assess the contribution of minimal residual cancer and genetic aberrations in clinically normal upper aerodigestive tract mucosa to treatment failure. Eighteen consecutive patients with oral tumors, with conventional clear margins, have been followed for a minimum of 36 months. Molecular assessment identified tumor-positive surgical margins for 6 of 11 assessable patients and additional tumor-positive lymph nodes for three cases. Disseminated malignant cells were detected in the hematopoietic cell compartment for six cases, and one patient had molecular evidence of field cancerization. Locoregional recurrence developed in five patients with tumors harboring a p53 gene mutation; four of these were associated with tumor-positive surgical margins, and one was associated with molecular evidence of field cancerization. Radiotherapy to the primary site did not prevent development of local recurrence when the residual tumor harbored a p53 gene mutation. Three of six cases with a tumor-positive bone marrow aspirate developed distant metastases. These findings reveal that molecular and immunocytochemical detection of minimal residual cancer and field cancerization can help identify patients who may develop locoregional or distant recurrence and justify further studies to evaluate the contribution of these remaining malignant cells to treatment failure.

This article has been cited by other articles:

				C. Alix-Panabieres, S. Riethdorf, and K. Pantel Circulating Tumor Cells and Bone Marrow Micrometastasis Clin. Cancer Res., August 15, 2008; 14(16): 5013 - 5021. [Abstract] [Full Text] [PDF]

				K. Pantel, C. Alix-Panabieres, and S. Riethdorf Circulating Tumor Cells: Detection and Clinical Relevance Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 603 - 610. [Abstract] [Full Text] [PDF]

				W. H. Westra and D. Sidransky Fluorescence Visualization in Oral Neoplasia: Shedding Light on an Old Problem. Clin. Cancer Res., November 15, 2006; 12(22): 6594 - 6597. [Full Text] [PDF]

				B. J.M. Braakhuis, R. H. Brakenhoff, and C. R. Leemans Second Field Tumors: A New Opportunity for Cancer Prevention? Oncologist, August 1, 2005; 10(7): 493 - 500. [Abstract] [Full Text] [PDF]

				M. Hockel and N. Dornhofer The Hydra Phenomenon of Cancer: Why Tumors Recur Locally after Microscopically Complete Resection Cancer Res., April 15, 2005; 65(8): 2997 - 3002. [Abstract] [Full Text] [PDF]

				S. Temam, O. Casiraghi, J.-B. Lahaye, J. Bosq, X. Zhou, M. Julieron, G. Mamelle, J. J. Lee, L. Mao, B. Luboinski, et al. Tetranucleotide Microsatellite Instability in Surgical Margins for Prediction of Local Recurrence of Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., June 15, 2004; 10(12): 4022 - 4028. [Abstract] [Full Text] [PDF]

				M. P. Tabor, R. H. Brakenhoff, H. J. Ruijter-Schippers, J. A. Kummer, C. R. Leemans, and B. J. M. Braakhuis Genetically Altered Fields as Origin of Locally Recurrent Head and Neck Cancer: A Retrospective Study Clin. Cancer Res., June 1, 2004; 10(11): 3607 - 3613. [Abstract] [Full Text] [PDF]

				V. M. M. van Houten, C. R. Leemans, J. A. Kummer, J. Dijkstra, D. J. Kuik, M. W. M. van den Brekel, G. B. Snow, and R. H. Brakenhoff Molecular Diagnosis of Surgical Margins and Local Recurrence in Head and Neck Cancer Patients: A Prospective Study Clin. Cancer Res., June 1, 2004; 10(11): 3614 - 3620. [Abstract] [Full Text] [PDF]

				S. V. Harden, D. C. Thomas, N. Benoit, K. Minhas, W. H. Westra, J. A. Califano, W. Koch, and D. Sidransky Real-Time Gap Ligase Chain Reaction: A Rapid Semiquantitative Assay for Detecting p53 Mutation at Low Levels in Surgical Margins and Lymph Nodes from Resected Lung and Head and Neck Tumors Clin. Cancer Res., April 1, 2004; 10(7): 2379 - 2385. [Abstract] [Full Text] [PDF]

				M. Partridge, R. Brakenhoff, E. Phillips, K. Ali, R. Francis, R. Hooper, K. Lavery, A. Brown, and J. Langdon Detection of Rare Disseminated Tumor Cells Identifies Head and Neck Cancer Patients at Risk of Treatment Failure Clin. Cancer Res., November 1, 2003; 9(14): 5287 - 5294. [Abstract] [Full Text] [PDF]

				P. K. Ha and J. A. Califano THE MOLECULAR BIOLOGY OF MUCOSAL FIELD CANCERIZATION OF THE HEAD AND NECK Crit. Rev. Oral. Biol. Med., September 1, 2003; 14(5): 363 - 369. [Abstract] [Full Text] [PDF]

				B. J. M. Braakhuis, C. R. Leemans, R. H. Brakenhoff, M. P. Rosin, W. L. Lam, and L. Zhang Correspondence re: M. P. Rosin et al., 3p14 and 9p21 Loss Is a Simple Tool for Predicting Second Oral Malignancy at Previously Treated Oral Cancer Sites. Cancer Res., 62: 6447-6450, 2002. Cancer Res., August 15, 2003; 63(16): 5167 - 5169. [Full Text] [PDF]

				B. J. M. Braakhuis, M. P. Tabor, J. A. Kummer, C. R. Leemans, and R. H. Brakenhoff A Genetic Explanation of Slaughter's Concept of Field Cancerization: Evidence and Clinical Implications Cancer Res., April 15, 2003; 63(8): 1727 - 1730. [Abstract] [Full Text] [PDF]

				E. J. C. Nieuwenhuis, L. H. Jaspars, J. A. Castelijns, B. Bakker, R. G. A. Wishaupt, F. Denkers, C. R. Leemans, G. B. Snow, and R. H. Brakenhoff Quantitative Molecular Detection of Minimal Residual Head and Neck Cancer in Lymph Node Aspirates Clin. Cancer Res., February 1, 2003; 9(2): 755 - 761. [Abstract] [Full Text] [PDF]

				R. Oakley, E. Phillips, R. Hooper, D. Wilson, and M. Partridge A Preclinical Model of Minimal Residual Cancer in the Muscle Highlights Challenges Associated with Adenovirus-mediated p53 Gene Transfer Clin. Cancer Res., June 1, 2002; 8(6): 1984 - 1994. [Abstract] [Full Text] [PDF]

				A. Forastiere, W. Koch, A. Trotti, and D. Sidransky Head and Neck Cancer N. Engl. J. Med., December 27, 2001; 345(26): 1890 - 1900. [Full Text] [PDF]