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The predictive value of p53, MDM-2, cyclin D1 and Ki67 in the progression from low-grade dysplasia towards carcinoma of the larynx

Published online by Cambridge University Press:  29 June 2007

Lorenzo Pignataro ,
Pasquale Capaccio ,
Giancarlo Pruneri ,
Nadia Carboni ,
Roberto Buffa ,
Antonino Neri  and
Antonio Ottaviani
Lorenzo Pignataro*
Affiliation:
Clinica Otorinolaringoiatrica, Servizio di Ematologia, Istituto di Scienze Mediche, Università di Milano, Ospedale Maggiore di Milano, I.R.C.C.S., 20122, Milan, Italy
Pasquale Capaccio
Affiliation:
Clinica Otorinolaringoiatrica, Servizio di Ematologia, Istituto di Scienze Mediche, Università di Milano, Ospedale Maggiore di Milano, I.R.C.C.S., 20122, Milan, Italy
Giancarlo Pruneri
Affiliation:
II Servizio di Anatomia Patologica, Servizio di Ematologia, Istituto di Scienze Mediche, Università di Milano, Ospedale Maggiore di Milano, I.R.C.C.S., 20122, Milan, Italy
Nadia Carboni
Affiliation:
II Servizio di Anatomia Patologica, Servizio di Ematologia, Istituto di Scienze Mediche, Università di Milano, Ospedale Maggiore di Milano, I.R.C.C.S., 20122, Milan, Italy
Roberto Buffa
Affiliation:
II Servizio di Anatomia Patologica, Servizio di Ematologia, Istituto di Scienze Mediche, Università di Milano, Ospedale Maggiore di Milano, I.R.C.C.S., 20122, Milan, Italy
Antonino Neri
Affiliation:
Laboratorio di Ematologia Sperimentale e Genetica Molecolare, Servizio di Ematologia, Istituto di Scienze Mediche, Università di Milano, Ospedale Maggiore di Milano, I.R.C.C.S., 20122, Milan, Italy
Antonio Ottaviani
Affiliation:
Clinica Otorinolaringoiatrica, Servizio di Ematologia, Istituto di Scienze Mediche, Università di Milano, Ospedale Maggiore di Milano, I.R.C.C.S., 20122, Milan, Italy
*
Address for correspondence: Lorenzo Pignataro, M.D., Istituto di Clinica Otorhinolaringoiatrica IOspedale Maggiore, I.R.C.C.S. Via F. Sforza, 35 20122 Milano, Italy. Fax 0039 2 55180809
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Abstract

To evaluate the predictive role of the oncogenes p53, MDM-2 and cyclin D1, and the proliferative marker Ki67, in the progression from low-grade dysplasia to carcinoma of the larynx. We studied immunohistochemically a series of 32 low-grade pre-neoplastic laryngeal lesions, 10 of which progressed to invasive carcinoma. Immunoreactivity in more than 10 per cent of the dysplastic cells was detected in five cases immunostained with anti-p53 (≈ 15 per cent), in two with anti-MDM-2 (≈ six per cent), and 11 with anti-Ki67 antibodies (≈ 34 per cent), whereas none of the cases showed cyclin D1 overexpression. No significant association was found between p53 and MDM-2 immunoreactivity and the evolution to carcinoma; on the contrary, Ki67 expression was detectable in all but one of the 10 cases developing an infiltrative tumour (90 per cent), and in two of the 22 cases that did not progress (≈ nine per cent) (p = 0.01). These findings indicate that immunohistochemical assessment of the proliferative index in bioptic samples of dysplastic laryngeal mucosa may be useful in selecting patients who should undergo a more specific follow-up evaluation.

Keywords

OncogenesTumour markers, biologicalInununohistochemistrylaryngeal neoplasms
Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 112 , Issue 5 , May 1998 , pp. 455 - 459
Copyright
Copyright © JLO (1984) Limited 1998

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Footnotes

Presented in part at the 20th National Congress of the Italian Society of Surgical Oncology, Rome, Italy, October 17–18, 1996.

References

Ahomadegbe, J. C., Barrois, M., Fogel, S., Le Bihan, M. L., Douc-Rasy, S., Duvillard, P., Armand, J. P., Riou, G. (1995) High incidence of p53 alterations (mutation, deletion, overexpression) in head and neck primary tumors and metastases; absence of correlation with clinical outcome. Frequent protein overexpression in normal epithelium and in early non-invasive lesions. Oncogene 10: 1217–1227.Google ScholarPubMed
Armitage, P., Berry, G. (1991) Statistical methods in medical research Blackwell Scientific Publications, Oxford, pp 125–132.Google Scholar
Bartkova, J., Lukas, J., Strauss, M., Bartek, J. (1995) Cyclin D1 oncoprotein aberrantly accumulates in malignancies of diverse histogenesis. Oncogene 10: 775–778.Google ScholarPubMed
Blackwell, K. E., Fu, Y.-S., Calcaterra, T. C. (1995) Laryngeal dysplasma. A clinicopathologic study. Cancer 75(2): 457–463.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Brown, D. C., Gatter, K. C. (1990) Monoclonal antibody Ki-67: its use in histopathology. Histopathology 17:489–503.CrossRefGoogle ScholarPubMed
Bulten, J., Van Der Laak, J. A. W. M., Gemmink, J. H., Pahlplatz, M. M. M., De Wilde, P. C. M., Hanselaar, A. G. J. M. (1996) M1B1, a promising marker for the classification of cervical intraepithelial neoplasia. Journal of Pathology 178: 268–273.3.0.CO;2-4>CrossRefGoogle Scholar
Chen, X., Bargonetti, J., Prives, C. (1995) p53, through p21 (WAF1/CIP1), induces cyclin D1 synthesis. Cancer Research 55: 4257–4263.Google ScholarPubMed
Crissman, J. D., Fu, Y. S. (1986) Intraepithelial neoplasia of the larynx: a clinicopathologic study of six cases with DNA analysis. Archives of Otolaryngology-Head and Neck Surgery 112: 522–528.CrossRefGoogle ScholarPubMed
Dolcetti, R., Doglioni, C., Maestro, R., Gasparotto, D., Barzan, L., Pastore, A., Romanelli, M., Boiocchi, M. (1992) p53 over-expression is an early event in the development of human squamous-cell carcinoma of the larynx: genetic and prognostic implications. International Journal of Cancer 52: 178–182.CrossRefGoogle ScholarPubMed
Gerdes, J., Becker, M. H., Key, G., Cattoretti, G. (1992) Immunohistochemical detection of tumour growth fraction (Ki67 antigen) in formalin-fixed and routinely processed tissues. Journal of Pathology 168: 85.CrossRefGoogle Scholar
Girod, S. C., Krueger, G., Pape, H-D. (1993) p53 and Ki67 expression in preneoplastic and neoplastic lesions of the oral mucosa. International Journal of Oral Maxillofacial Surgery 22: 285–288.CrossRefGoogle Scholar
Kernohan, N. M., Cox, L. S. (1996) Regulation of apoptosis by bcl-2 and its related proteins: immunochemical challenges and therapeutic implications. Journal of Pathology 179:1–3.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
Oliner, J. D., Pietenpol, J. A., Thiagalingam, S., Gyuris, J., Kinzler, W., Vogelstein, B. (1993) Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature 362: 857.CrossRefGoogle ScholarPubMed
Polkowski, W., Van Lanschot, J. J. B., Ten Kate, F. J. W., Baak, J. P. A., Tytgat, G. N. J., Obertop, H., Voorn, W. J., Offerhaus, G. J. A. (1995) The value of p53 and Ki67 as markers for tumour progression in the Barrett's dysplasiacarcinoma sequence. Surgical Oncology 4: 163–171.CrossRefGoogle ScholarPubMed
Pruneri, G., Pignataro, L., Fracchiolla, N. S., Ferrero, S., Capaccio, P., Carboni, N., Ottaviani, A., Maiolo, A. T., Neri, A., Buffa, R. (1996) p53 protein expression in laryngeal squamous cell carcinomas bearing wild-type and mutated p53 gene. Histopathology 28: 513–519.CrossRefGoogle ScholarPubMed
Pruneri, G., Pignataro, L., Carboni, N., Luminari, S., Capaccio, P., Neri, A., Buffa, R. (1997) MDM-2 oncoprotein overexpression frequently occurs in laryngeal squamous cell carcinomas in absence of gene amplification, and it is associated with wild-type p53 accumulation. Modern Pathology 10(8): 785–792.Google Scholar
Quelle, D. E., Ashmun, R. A., Shurtleff, S. A., Kato, J., Bar-Sagi, D., Roussel, M. F., Sherr, C. J. (1993) Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes Development 7: 1559–1571.CrossRefGoogle ScholarPubMed
Sarbia, M., Bittinger, F., Porschen, R., Dutkowski, P., Willers, R., Gabbert, H. E. (1996) The prognostic significance of tumour cell proliferation in squamous cell carcinomas of the oesophagus. British Journal of Cancer 74: 1012–1016.CrossRefGoogle ScholarPubMed
Sauter, E. R., Cleveland, D., Trock, B., Ridge, J. A., Klein-Szanto, J. P. (1994) p53 is overexpressed in 50 per cent of pre-invasive lesions of head and neck epithelium. Carcino-genesis 15(10): 2269–2274.CrossRefGoogle Scholar
Shanmugaratnam, K., Sobin, I. N. (1991) Histological typing of tumours of the upper respiratory tract and ear. 2nd Edition. Springer Verlag, Berlin, pp 26–29.CrossRefGoogle Scholar
Shin, D. M., Kim, J., Ro, J. Y., Hittelman, J., Roth, J. A., Hong, W. K., Hittelman, W. N. (1994) Activation of p53 gene expression in premalignant lesions during head and neck carcinogensis. Cancer Research 54: 321–326.Google Scholar
Tunkegar, M. F., Gatter, K. C., Dunnill, M. S., Mason, D. Y. (1991) Ki67 immunostaining and survival in operable lung cancer. Histopathology 19: 545–548.Google Scholar
Uhlman, D. L., Adams, G., Knapp, D., Aeppli, D. M., Niehans, G. (1996) Immunohistochemical staining for markers of future neoplastic progression in the larynx. Cancer Research 56: 2199–2205.Google ScholarPubMed
Vogelstein, B., Kinzler, K. W. (1992) p53 function and dysfunction. Cell 70: 523.CrossRefGoogle Scholar
Zidar, N., Gale, N., Cor, A., Kambic, V. (1996) Expression of Ki67 antigen and proliferative cell nuclear antigen in benign and malignant epithelial lesions of the larynx. Journal of Laryngology and Otology 110: 440–445.CrossRefGoogle ScholarPubMed