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RETRACTED: When is an oral leukoplakia premalignant?
Oral Oncology 38 (2002) 813–814 www.elsevier.com/locate/oraloncology
Letter to the Editor
When is an oral leukoplakia premalignant? Jon Sudbøa,*, Albrecht Reithb a
nostics [4]. The reproducibility, and therefore the prognostic value of histological grading may possibly be improved by a strictly quantitative approach [5]. A recent article in this journal showed that large scale genomic aberrations (DNA aneuploidy) could occur in oral lesions that from the histological assessment by four independent, trained pathologists should have been without any malignant potential. From these lesions, a subset of specimens with aberrant DNA content in their cell nuclei subsequently gave rise to oral carcinomas [6]. Thus, from a biological point of view, these lesions were premalignant, whereas by traditional histological assessment, they were not. In another study, 100 out 150 patients with lesions classified as dysplasias (and therefore presumably premalignant), but without genetic aberrations, did not develop carcinomas during a longterm follow-up [7]. Taking into consideration these findings and a review of the current literature, one is forced to admit that the morphological parameters considered by traditional histological assessment do not always reflect ongoing biological processes in tissues. On the other hand, genetic markers are emerging that seem to be of clinical value in assessing the risk of malignant transformation in oral leukoplakias or erythroplakias [6–9]. Information from such analyses may re-define risk assessment in oral leukoplakias and even guide treatment [10]. It is time to establish standard genetic and molecular assays to help plan the management of oral leukoplakias.
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ET
R
AC
Ku¨ffer and Lombardi are to be commended for their February 2002 review focusing on the semantics and biology of precursor lesions to oral cancer [1]. An unequivocal and simplified terminology for this group of lesions is badly needed. We agree with the authors that clinical findings must be supported by additional analyses to reveal whether a putative precursor lesion in fact has a malignant potential or not. The initial observation leading to a work-up in this group of patients most often is an oral leukoplakia. The concept of leukoplakia is troublesome for two reasons: first, it is negatively defined, considered only when other diagnoses have been ruled out. Second, leukoplakias are clinical entities that may harbour a wide range of histological, molecular and genetic changes, many of which are not associated with malignant transformation. Therefore, as the authors state, using the term ‘‘leukoplakia’’ synonymous with ‘‘premalignant’’ is misleading. What additional analyses should be done in order to predict the clinical course of oral leukoplakias? Ku¨ffer and Lombardi advocate histological assessment as an approach. However, we are conserned about the prognostic value of histological typing and grading of oral leukoplakias. For a decision instrument to be clinically valuable, it must be shown to be reproducible among observers [2]. However, Karabulut and co-workers, in a classic paper, documented the lack of inter- and intra-observer agreement in typing and grading of oral dysplastic lesions, which is the histological entity most often associated with malignant transformation of the oral mucosa [3]. This lack of reproducibility inevitably reduces the prognostic value of such typing and grading. Regrettably, no prognostically reliable molecular markers are established within the scope of routine diag-
TE
Received 5 April 2002; accepted 17 April 2002
D
Department of Medical Oncology and Radiotherapy, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway b Department of Pathology, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway
* Corresponding author. Tel.: +47-2293-4230; fax ++47-22935627. E-mail address: [email protected] (J. Sudbø).
References [1] Ku¨ffer R, Lombardi T. Premalignant lesions of the oral mucosa. A discussion about the place of oral intraepithelial neoplasia (OIN) Oral Oncol 2002;38:125–30. [2] Wasson JH, Sox HC, Neff RK, Goldman L. Clinical prediction rules. Applications and methodological standards. N Engl J Med 1985;313:793–9.
1368-8375/02/$ - see front matter # 2002 Elsevier Science Ltd. All rights reserved. PII: S1368-8375(02)00021-0
814
J. Sudbø / Oral Oncology 38 (2002) 813–814 [7] Sudbø J, Kildal W, Risberg B, Koppang HS, Danielsen HE, Reith A, et al. DNA content as a prognostic marker in patients with oral leukoplakias. N Engl J Med 2001;344:1270–8. [8] Sudbø J, Kildal W, Johannessen AC, Koppang HS, Sudbø A, Danielsen HE, et al. Gross genomic aberrations in precancers: clinical implications of a long-term follow-up study in oral erythroplakias. J Clin Oncol 2002;20:456–62. [9] Lippman SM, Hong WK. Molecular markers of the risk of oral cancer [editorial]. N Engl J Med 2001;344:1323–6. [10] Lee JJ, Hong WK, Hittelman WN, Mao L, Lotan R, Shin DM, et al. Predicting cancer development in oral leukoplakia: ten years of translational research. Clin Cancer Res 2000;6: 1702–10.
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AC
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[3] Karabulut A, Reibel J, Therkildsen MH, Praetorius F, Nielsen HW, Dabelsteen E. Observer variability in the histologic assessment of oral premalignant lesions. J Oral Pathol Med 1995;24: 198–200. [4] Warnakulasuriya S. Lack of molecular markers to predict malignant potential of oral precancer [editorial; comment]. J Pathol 2000;190:407–9. [5] Sudbø J, Bankfalvi A, Bryne M, Marcelpoil R, Boysen M, Piffko J, et al. Prognostic value of graph theory-based tissue architecture analysis in carcinomas of the tongue. Lab Invest 2000;80:1881–9. [6] Sudbø J, Ried T, Bryne M, Kildal W, Danielsen HE, Reith A. Abnormal DNA content predicts the occurence of carcinomas in non-dysplastic oral white patches. Oral Oncol 2000;37:558–65.
Letter to the Editor
When is an oral leukoplakia premalignant? Jon Sudbøa,*, Albrecht Reithb a
nostics [4]. The reproducibility, and therefore the prognostic value of histological grading may possibly be improved by a strictly quantitative approach [5]. A recent article in this journal showed that large scale genomic aberrations (DNA aneuploidy) could occur in oral lesions that from the histological assessment by four independent, trained pathologists should have been without any malignant potential. From these lesions, a subset of specimens with aberrant DNA content in their cell nuclei subsequently gave rise to oral carcinomas [6]. Thus, from a biological point of view, these lesions were premalignant, whereas by traditional histological assessment, they were not. In another study, 100 out 150 patients with lesions classified as dysplasias (and therefore presumably premalignant), but without genetic aberrations, did not develop carcinomas during a longterm follow-up [7]. Taking into consideration these findings and a review of the current literature, one is forced to admit that the morphological parameters considered by traditional histological assessment do not always reflect ongoing biological processes in tissues. On the other hand, genetic markers are emerging that seem to be of clinical value in assessing the risk of malignant transformation in oral leukoplakias or erythroplakias [6–9]. Information from such analyses may re-define risk assessment in oral leukoplakias and even guide treatment [10]. It is time to establish standard genetic and molecular assays to help plan the management of oral leukoplakias.
R
ET
R
AC
Ku¨ffer and Lombardi are to be commended for their February 2002 review focusing on the semantics and biology of precursor lesions to oral cancer [1]. An unequivocal and simplified terminology for this group of lesions is badly needed. We agree with the authors that clinical findings must be supported by additional analyses to reveal whether a putative precursor lesion in fact has a malignant potential or not. The initial observation leading to a work-up in this group of patients most often is an oral leukoplakia. The concept of leukoplakia is troublesome for two reasons: first, it is negatively defined, considered only when other diagnoses have been ruled out. Second, leukoplakias are clinical entities that may harbour a wide range of histological, molecular and genetic changes, many of which are not associated with malignant transformation. Therefore, as the authors state, using the term ‘‘leukoplakia’’ synonymous with ‘‘premalignant’’ is misleading. What additional analyses should be done in order to predict the clinical course of oral leukoplakias? Ku¨ffer and Lombardi advocate histological assessment as an approach. However, we are conserned about the prognostic value of histological typing and grading of oral leukoplakias. For a decision instrument to be clinically valuable, it must be shown to be reproducible among observers [2]. However, Karabulut and co-workers, in a classic paper, documented the lack of inter- and intra-observer agreement in typing and grading of oral dysplastic lesions, which is the histological entity most often associated with malignant transformation of the oral mucosa [3]. This lack of reproducibility inevitably reduces the prognostic value of such typing and grading. Regrettably, no prognostically reliable molecular markers are established within the scope of routine diag-
TE
Received 5 April 2002; accepted 17 April 2002
D
Department of Medical Oncology and Radiotherapy, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway b Department of Pathology, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway
* Corresponding author. Tel.: +47-2293-4230; fax ++47-22935627. E-mail address: [email protected] (J. Sudbø).
References [1] Ku¨ffer R, Lombardi T. Premalignant lesions of the oral mucosa. A discussion about the place of oral intraepithelial neoplasia (OIN) Oral Oncol 2002;38:125–30. [2] Wasson JH, Sox HC, Neff RK, Goldman L. Clinical prediction rules. Applications and methodological standards. N Engl J Med 1985;313:793–9.
1368-8375/02/$ - see front matter # 2002 Elsevier Science Ltd. All rights reserved. PII: S1368-8375(02)00021-0
814
J. Sudbø / Oral Oncology 38 (2002) 813–814 [7] Sudbø J, Kildal W, Risberg B, Koppang HS, Danielsen HE, Reith A, et al. DNA content as a prognostic marker in patients with oral leukoplakias. N Engl J Med 2001;344:1270–8. [8] Sudbø J, Kildal W, Johannessen AC, Koppang HS, Sudbø A, Danielsen HE, et al. Gross genomic aberrations in precancers: clinical implications of a long-term follow-up study in oral erythroplakias. J Clin Oncol 2002;20:456–62. [9] Lippman SM, Hong WK. Molecular markers of the risk of oral cancer [editorial]. N Engl J Med 2001;344:1323–6. [10] Lee JJ, Hong WK, Hittelman WN, Mao L, Lotan R, Shin DM, et al. Predicting cancer development in oral leukoplakia: ten years of translational research. Clin Cancer Res 2000;6: 1702–10.
R
ET
R
AC
TE
D
[3] Karabulut A, Reibel J, Therkildsen MH, Praetorius F, Nielsen HW, Dabelsteen E. Observer variability in the histologic assessment of oral premalignant lesions. J Oral Pathol Med 1995;24: 198–200. [4] Warnakulasuriya S. Lack of molecular markers to predict malignant potential of oral precancer [editorial; comment]. J Pathol 2000;190:407–9. [5] Sudbø J, Bankfalvi A, Bryne M, Marcelpoil R, Boysen M, Piffko J, et al. Prognostic value of graph theory-based tissue architecture analysis in carcinomas of the tongue. Lab Invest 2000;80:1881–9. [6] Sudbø J, Ried T, Bryne M, Kildal W, Danielsen HE, Reith A. Abnormal DNA content predicts the occurence of carcinomas in non-dysplastic oral white patches. Oral Oncol 2000;37:558–65.