Objective: The prognostic value of pRb and p53 altered expression in non-small cell lung cancer (NSCLC) remains debatable. We assessed the occurrence of altered pRb and p53 protein expression, and the prognostic value of these assays considered as separate and combined variables in operable NSCLC. The study group included 195 NSCLC consecutive patients from one institution who underwent curative pulmonary resection between 1994 and 1999. Methods: Expression of pRb and p53 was assessed immunohistochemically with the use of monoclonal antibodies (LM95.1 and Pab 1801, Oncogene Science, respectively). Results: A lack of pRb and abnormal p53 protein expression were found in 57 (29%) and 92 samples (47%), respectively, whereas both abnormalities (pRb–/p53+) occurred in 24 samples (12%). There was no relationship between altered pRb/p53 expression and major clinico-pathological characteristics, neither was there a significant difference in disease-free and overall survival between particular groups of patients with tumors carrying four possible pRb/p53 phenotypes. In uni- and multivariate analysis, the only variable associated with shortened disease-free and overall survival was stage of disease (p < 0.001) and degree of tumor differentiation (p = 0.005). Conclusion: These results suggest that altered pRb and p53 expression does not provide prognostic information in operable NSCLC patients.

1.
Knudson AG: Mutation and cancer: Statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971;68:820–823.
2.
Horsthemke B, Brandt B, Albrecht B, Passarge E: Deletion in one allele and a rare neutral DNA alteration in the other allele of the RB1 gene in a patient with bilateral retinoblastoma. Am J Med Genet 1992;44:255.
3.
Levine AJ, Momand J, Finlay CA: The p53 tumour suppressor gene. Nature 1991;351:453–456.
4.
Lane DP: Cancer. p53, guardian of the genome. Nature 1992;358:15–16.
5.
Levine AJ: p53, the cellular gatekeeper for growth and division. Cell 1997;88:323–331.
6.
Nataraj AJ, Trent JC, Ananthaswamy HN: p53 gene mutations and photocarcinogenesis. Photochem Photobiol 1995;62:218–230.
7.
Sherr CJ: Cancer cell cycle. Science 1996;274:1672–1677.
8.
Giaccia AJ, Kastan MB: The complexity of p53 modulation: Emerging patterns from divergent signals. Genes Dev 1998;12:2973–2983.
9.
Maheswaran S, Englert C, Bennett P, Heinrich G, Haber DA: The WT1 gene product stabilizes p53 and inhibits p53-mediated apoptosis. Genes Dev 1995;9:2143–2156.
10.
Morgenbesser SD, Williams BO, Jacks T, De Pinho RA: p53-dependent apoptosis produced by Rb-deficiency in the developing mouse lens. Nature 1994;371:72–74.
11.
Mitsudomi T, Hamajima N, Ogawa M, Takahashi T: Prognostic significance of p53 alterations in patients with non-small cell lung cancer: A meta-analysis. Clin Cancer Res 2000;6:4055–4063.
12.
Hommura F, Dosaka-Akita H, Kinoshita I, Mishina T, Hiroumi H, Ogura S, Katoh H, Kawakami Y: Predictive value of expression of p16INK4A, retinoblastoma and p53 proteins for the prognosis of non-small-cell lung cancers. Br J Cancer 1999;81:696–701.
13.
Xu HJ, Quinlan DC, Davidson AG, Hu SX, Summers CL, Li J, Benedict WF: Altered retinoblastoma protein expression and prognosis in early-stage non-small-cell lung carcinoma. J Natl Cancer Inst 1994,86:695–699.
14.
Xu HJ, Cagle PT, Hu SX, Li J, Benedict WF: Altered retinoblastoma and p53 protein status in non-small cell carcinoma of the lung: Potential synergistic effects on prognosis. Clin Cancer Res 1996;2:1169–1176.
15.
Lee YC, Chang YL, Luh SP, Lee JM, Chen JS: Significance of p53 and Rb protein expression in surgically treated non-small cell lung cancers. Ann Thorac Surg 1999;68:343–347.
16.
Kratzke RA, Greatens TM, Rubins JB, Maddaus MA, Niewoehner DE, Niehans GA, Geradts J: Rb and p16INK4a expression in resected non-small cell lung tumors. Cancer Res 1996;56:3415–3420.
17.
Reissmann PT, Koga H, Takahashi R, Figlin RA, Holmes EC, Piantadosi S, Cordon-Cardo C, Slamon DJ: Inactivation of the retinoblastoma susceptibility gene in non-small-cell lung cancer. The Lung Cancer Study Group. Oncogene 1993;8:1913–1919.
18.
Betticher DC, White GR, Vonlanthen S, Liu X, Kappeler A, Altermatt HJ, Thatcher N, Heighway J: G1 control gene status is frequently altered in resectable non-small cell lung cancer. Int J Cancer 1997;74:556–562.
19.
Dosaka-Akita H, Hu SX, Fujino M, Harada M, Kinoshita I, Xu HJ, Kuzumaki N, Kawakami Y, Benedict WF: Altered retinoblastoma protein expression in nonsmall cell lung cancer: Its synergistic effects with altered ras and p53 protein status on prognosis. Cancer 1997;79:1329–1337.
20.
Greenblatt MS, Bennett WP, Hollstein M, Harris CC: Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 1994,54:4855–4878.
21.
Sobin LH, Wittekind C: TNM classification of malignant tumors. New York, UICC International Union Against Cancer/ Wiley-Liss, 1997.
22.
Jin M, Inoue S, Umemura T, Moriya J, Arakawa M, Nagashima K, Kato H: Cyclin D1, p16 and retinoblastoma gene product expression as a predictor for prognosis in non-small cell lung cancer at stages I and II. Lung Cancer 2001;34:207–218.
23.
Chen JT, Chen YC, Chen CY, Wang YC: Loss of p16 and/or pRb protein expression in NSCLC. An immunohistochemical and prognostic study. Lung Cancer 2001;31:163–170.
24.
Nishio M, Koshikawa T, Yatabe Y, Kuroishi T, Suyama M, Nagatake M, Sugiura T, Ariyoshi Y, Mitsudomi T, Takahashi T: Prognostic significance of cyclin D1 and retinoblastoma expression in combination with p53 abnormalities in primary, resected non-small cell lung cancers. Clin Cancer Res 1997;3:1051–1058.
25.
Sugio K, Tsukamoto S, Ushijima C, Yamazaki K, Kase S, Yamaguchi M, Ondo K, Yano T, Sugimachi K: Clinical significance of the Rb expression in adenocarcinoma of the lung. Anticancer Res 2001;21:1931–1935.
26.
Akin H, Yilmazbayhan D, Kilicaslan Z, Dilege S, Dogan O, Toker A, Kalayci G: Clinical significance of P16INK4A and retinoblastoma proteins in non-small cell lung carcinoma. Lung Cancer 2002;38:253–260.
27.
Brambilla E, Moro D, Gazzeri S, Brambilla C: Alterations of expression of Rb, p16(INK4A) and cyclin D1 in non-small cell lung carcinoma and their clinical significance. J Pathol 1999;188:351–360.
28.
Carbone DP, Mitsudomi T, Chiba I, Piantadosi S, Rusch V, Nowak JA, McIntire D, Slamon D, Gazdar A, Minna J: p53 immunostaining positivity is associated with reduced survival and is imperfectly correlated with gene mutations in resected non-small cell lung cancer. A preliminary report of LCSG 871. Chest 1994;106:377S–381S.
29.
Ebina M, Steinberg SM, Mulshine JL, Linnoila RI: Relationship of p53 overexpression and up-regulation of proliferating cell nuclear antigen with the clinical course of non-small cell lung cancer. Cancer Res 1994;54:2496–2503.
30.
Esposito V, Baldi A, De Luca A, Micheli P, Mazzarella G, Baldi F, Caputi M, Giordano A: Prognostic value of p53 in non-small cell lung cancer: Relationship with proliferating cell nuclear antigen and cigarette smoking. Hum Pathol 1997;28:233–237.
31.
Pastorino U, Andreola S, Tagliabue E, Pezzella F, Incarbone M, Sozzi G, Buyse M, Menard S, Pierotti M, Rilke F: Immunocytochemical markers in stage I lung cancer: Relevance to prognosis. J Clin Oncol 1997;15:2858–2865.
32.
Apolinario RM, van der Valk P, de Jong JS, Deville W, van Ark-Otte J, Dingemans AM, van Mourik JC, Postmus PE, Pinedo HM, Giaccone G: Prognostic value of the expression of p53, bcl-2, and bax oncoproteins, and neovascularization in patients with radically resected non-small cell lung cancer. J Clin Oncol 1997;15:2456–2466.
33.
Dworakowska D, Gozdz S, Jassem E, Badzio A, Kobierska G, Urbaniak A, Skokowski J, Damps I, Jassem J: Prognostic relevance of proliferating cell nuclear antigen and p53 expression in non-small cell lung cancer. Lung Cancer 2002;35:35–41.
34.
Dworakowska D, Jassem E, Wiedorn K, Dziadziuszko R, Kobierska G, Skokowski J, Bosse A, Jassem J: p53 and mdm2 expression in NSCLC: The lack of prognostic relevance. Eur Respir J 2001;18 (suppl 33), 230s, p 1591.
35.
Xu HJ, Hu SX, Benedict WF: Lack of nuclear RB protein staining in G0/middle G1 cells: Correlation to changes in total RB protein level. Oncogene 1991,6:1139–1146.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.