Abstract
AIMS: To examine the relation between the expression of p53 protein and the chaperone heat shock protein (hsp)72/73 in a population at high risk for gastric carcinoma, using single and double immunohistochemistry, and to compare the expression of these two proteins with clinicopathological features. METHODS: Monoclonal antibodies were used to investigate the expression of p53 protein and hsp72/73 in 46 human gastric carcinomas. A double immunohistochemical technique was used in cases that showed p53/hsp72/73 coexpression. RESULTS: p53 immunoreactivity was present in 11 tumours (24%), and hsp72/73 immunostaining was observed in 22 cases (48%). p53 expression was observed as nuclear staining in tumoral cells. hsp72/73 expression was demonstrated mainly as cytoplasmic staining, but six tumours also showed focal weak nuclear staining. Seven cases showed p53 and hsp72/73 coexpression with immunoreactivity for both proteins in the same neoplastic cells, three of them with focal areas of nuclear coexpression. p53 expression was seen more frequently in cases that showed a high intensity (+ + +) of hsp72/73 staining. No significant association was observed between the expression of the two proteins and clinicopathological features. CONCLUSIONS: More than half of our cases may have some impairment in p53 protein growth suppressive function, as a result of p53 gene alterations or complex formation. The positive correlation between p53 expression and intensity of hsp72/73 supports the postulate of a p53 regulating function for the chaperone hsp72/73. A high intensity of hsp72/73 immunohistochemical staining could be used as an indirect marker of p53 gene abnormalities.
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- Beckmann R. P., Mizzen L. E., Welch W. J. Interaction of Hsp 70 with newly synthesized proteins: implications for protein folding and assembly. Science. 1990 May 18;248(4957):850–854. doi: 10.1126/science.2188360. [DOI] [PubMed] [Google Scholar]
- Chang F., Syrjänen S., Tervahauta A., Syrjänen K. Tumourigenesis associated with the p53 tumour suppressor gene. Br J Cancer. 1993 Oct;68(4):653–661. doi: 10.1038/bjc.1993.404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chant I. D., Rose P. E., Morris A. G. Susceptibility of AML cells to in vitro apoptosis correlates with heat shock protein 70 (hsp 70) expression. Br J Haematol. 1996 Jun;93(4):898–902. doi: 10.1046/j.1365-2141.1996.d01-1737.x. [DOI] [PubMed] [Google Scholar]
- Ciocca D. R., Clark G. M., Tandon A. K., Fuqua S. A., Welch W. J., McGuire W. L. Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications. J Natl Cancer Inst. 1993 Apr 7;85(7):570–574. doi: 10.1093/jnci/85.7.570. [DOI] [PubMed] [Google Scholar]
- Correa P. A human model of gastric carcinogenesis. Cancer Res. 1988 Jul 1;48(13):3554–3560. [PubMed] [Google Scholar]
- Correa P. Is gastric carcinoma an infectious disease? N Engl J Med. 1991 Oct 17;325(16):1170–1171. doi: 10.1056/NEJM199110173251611. [DOI] [PubMed] [Google Scholar]
- Csendes A., Smok G., Medina E., Salgado I., Rivera R., Quitral M. Características evolutivas del cáncer gástrico 1958-1990. Rev Med Chil. 1992 Jan;120(1):36–42. [PubMed] [Google Scholar]
- Elledge R. M., Clark G. M., Fuqua S. A., Yu Y. Y., Allred D. C. p53 protein accumulation detected by five different antibodies: relationship to prognosis and heat shock protein 70 in breast cancer. Cancer Res. 1994 Jul 15;54(14):3752–3757. [PubMed] [Google Scholar]
- Harris C. C. 1995 Deichmann Lecture--p53 tumor suppressor gene: at the crossroads of molecular carcinogenesis, molecular epidemiology and cancer risk assessment. Toxicol Lett. 1995 Dec;82-83:1–7. doi: 10.1016/0378-4274(95)03643-1. [DOI] [PubMed] [Google Scholar]
- Jättelä M. Overexpression of major heat shock protein hsp70 inhibits tumor necrosis factor-induced activation of phospholipase A2. J Immunol. 1993 Oct 15;151(8):4286–4294. [PubMed] [Google Scholar]
- LAUREN P. THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION. Acta Pathol Microbiol Scand. 1965;64:31–49. doi: 10.1111/apm.1965.64.1.31. [DOI] [PubMed] [Google Scholar]
- Lane D. P., Crawford L. V. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261–263. doi: 10.1038/278261a0. [DOI] [PubMed] [Google Scholar]
- Lane D. P., Midgley C., Hupp T. Tumour suppressor genes and molecular chaperones. Philos Trans R Soc Lond B Biol Sci. 1993 Mar 29;339(1289):369–373. doi: 10.1098/rstb.1993.0036. [DOI] [PubMed] [Google Scholar]
- Macario A. J. Heat-shock proteins and molecular chaperones: implications for pathogenesis, diagnostics, and therapeutics. Int J Clin Lab Res. 1995;25(2):59–70. doi: 10.1007/BF02592359. [DOI] [PubMed] [Google Scholar]
- McBride O. W., Merry D., Givol D. The gene for human p53 cellular tumor antigen is located on chromosome 17 short arm (17p13). Proc Natl Acad Sci U S A. 1986 Jan;83(1):130–134. doi: 10.1073/pnas.83.1.130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Medina E. Las enfermedades digestivas en Chile: panorama epidemiológico. Rev Med Chil. 1988 Mar;116(3):282–288. [PubMed] [Google Scholar]
- Miller C., Mohandas T., Wolf D., Prokocimer M., Rotter V., Koeffler H. P. Human p53 gene localized to short arm of chromosome 17. 1986 Feb 27-Mar 5Nature. 319(6056):783–784. doi: 10.1038/319783a0. [DOI] [PubMed] [Google Scholar]
- Stenger J. E., Mayr G. A., Mann K., Tegtmeyer P. Formation of stable p53 homotetramers and multiples of tetramers. Mol Carcinog. 1992;5(2):102–106. doi: 10.1002/mc.2940050204. [DOI] [PubMed] [Google Scholar]
- Tahara E. Genetic alterations in human gastrointestinal cancers. The application to molecular diagnosis. Cancer. 1995 Mar 15;75(6 Suppl):1410–1417. doi: 10.1002/1097-0142(19950315)75:6+<1410::aid-cncr2820751504>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
- Tahara E. Molecular mechanism of stomach carcinogenesis. J Cancer Res Clin Oncol. 1993;119(5):265–272. doi: 10.1007/BF01212724. [DOI] [PubMed] [Google Scholar]
- Vogelstein B., Fearon E. R., Hamilton S. R., Kern S. E., Preisinger A. C., Leppert M., Nakamura Y., White R., Smits A. M., Bos J. L. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988 Sep 1;319(9):525–532. doi: 10.1056/NEJM198809013190901. [DOI] [PubMed] [Google Scholar]
- Vogelstein B., Kinzler K. W. The multistep nature of cancer. Trends Genet. 1993 Apr;9(4):138–141. doi: 10.1016/0168-9525(93)90209-z. [DOI] [PubMed] [Google Scholar]
- Vogelstein B., Kinzler K. W. p53 function and dysfunction. Cell. 1992 Aug 21;70(4):523–526. doi: 10.1016/0092-8674(92)90421-8. [DOI] [PubMed] [Google Scholar]
- Wright P. A., Quirke P., Attanoos R., Williams G. T. Molecular pathology of gastric carcinoma: progress and prospects. Hum Pathol. 1992 Aug;23(8):848–859. doi: 10.1016/0046-8177(92)90394-i. [DOI] [PubMed] [Google Scholar]
- Yamagata S., Hisamichi S. Epidemiology of cancer of the stomach. World J Surg. 1979 Nov;3(6):663–669. doi: 10.1007/BF01654784. [DOI] [PubMed] [Google Scholar]