Abstract
The restriction fragment length polymorphism of c-Ha-ras-1 and L-myc genes and expression of cell surface effector molecules were studied to determine their potential utility as markers for assessing risk of metastasis in 84 lung cancer patients. We performed a comparative study of primary lung carcinomas, metastases, adjacent tissues and blood samples in a group of patients with lung cancer of different histological types, grade of differentiation and presence of regional and distant metastasis. No differences in the frequency of c-Ha-ras-1 rare alleles were found between lung cancer patients and unaffected controls. The detection of common a4-allele seems to be associated with metastasis and low differentiation of lung carcinomas. S-allele of L-myc was observed in 82.6% of patients with metastatic lesions. Homozygosity of L-allele patients was not evidence for distant metastasis and only 17.4% of these patients have metastatic lesions of the lymph nodes. The expression of HLA class I and receptor of transferrin (TrRec) were tested immunohistochemically in the same patients. In the group of squamous cell carcinomas with regional metastases the expression of HLA class I antigens was decreased [7/21 (33.3%) positive staining tumors versus 13/20 (65.0%) in the group without metastases]. The opposite situation was observed for TrRec. The data of restriction fragment length polymorphism of oncogenes and expression of two cell surface effector molecules, identified in the same patients, were combined. The registration of more than one poor marker, tested in individuals with squamous cell carcinoma, closely correlated with dissemination and advanced stage of the disease. Nearly 90% (20/22) of patients with well and moderately differentiated tumor revealed metastatic lesions versus 6.6% (1/15) of patients with manifestation of a single poor marker. Finally, proposals could be made for the development of a risk group that incorporates both clinical and molecular biology features in the prediction of metastasis.
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Krontiris TG, Devlin B, Karp DD, Robert NJ and Risch N, 1993, An association between the risk of cancer and mutations in the HrasI minisatellite locus. NEJ Med, 329, 517–23.
Vineis P and Caporaso N, 1991, The analysis of restriction fragment length polymorphism in human cancer: a review from an epidemiological perspective. Int J Cancer, 47, 26–30.
Capon DJ, Chen EY, Levinson D, Seeburg PH and Geoddel DV, 1983, Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature, 302, 33.
Krontiris TG, Dimartino NA, Colb M, Mitcheson HD and Parkinson DR, 1986, Human restriction fragment length polymorphism and cancer risk assessment. J Cell Biochem, 30, 319–29.
Ryberg D, Tefre T, Ovrevo S, et al. 1990, Ha-ras-1 alleles in Norwegian lung cancer patients. Hum Genet, 86, 40–4.
Sugimura H, Caporaso NE, Modali RV, et al. 1990, Association of rare alleles of the Harvey ras protooncogene locus with lung cancer. Cancer Res, 50, 1857–62.
Heigway J, Thatcher N, Cerny T and Hasleton PS, 1986, Genetic predisposition to lung cancer. Br J Cancer, 53, 453–7.
Kawashima K, Nomura S, Hirai H, et al. 1992, Correlation of the L-myc RFLP with metastasis, prognosis and multiple cancer in lung-cancer patients. Int J Cancer, 50, 557–61.
Kato M, Togushida J, Honda K, et al. 1990, Elevated frequency of specific allele of the L-myc gene in male patients with bone and soft-tissue sarcomas. Int J Cancer, 45, 47–9.
Champeme MH, Bieche I, Latil A, Hagene K and Lidereau R, 1992, Association between restriction fragment length polymorphism of the L-myc gene and lung metastasis in human breast cancer. Int J Cancer, 50, 6–9.
Johnson IP, Staid BG, Holzmann B, Schwable W and Riethmuller G, 1989, De novo expression of intercellular-adhesion molecule I in melanoma correlates with increased risk of metastasis. Proc Natl Acad Sci USA, 86, 641–4.
Kondo K, Noguchi M, Mukai K, et al. 1990, Transferrin receptor expression in adenocarcinoma of the lung as a histopathologic indicator of prognosis. Chest, 97, 1367–71.
Garrido F, Cabrera T, Concha A, Glew S, RuizCabello F and Stern PL, 1993, Natural history of HLA expression during tumour development. Immunol Today, 14, 491–9.
Passlick B, Izbicki I and Simmel S, 1994, Expression of major histocompatibility class I and class II antigens and intercellular adhesion molecule I on operable non small cell lung carcinomas: frequency and prognostic significance. Eur J Cancer, 30, 376–81.
Nau MM, Brooks BJ, Battey J, et al. 1985, L-myc, a new myc-related gene amplified and expressed in human small-cell lung cancer. Nature, 318, 69–73.
Maniatis T, Sambrook J and Fritsch EF, 1992, Molecular Cloning. A Laboratory Manual.
Tefre T, Borresen A-L, Aamdal S and Brogger A, 1990, Studies of the L-myc DNA polymorphism and relation to metastasis in Norwegian lung cancer patients. Br J Cancer, 61, 809–12.
Thelu M-A, Zarski J-P, Froissart B, Rashall M and Seigneurin J-M, 1993, c-Ha-ras polymorphism in patients with hepatocellular carcinoma. Gastroenterol Clin Biol, 17, 903–7.
Wyllie FS, Wynford-Thomas V, Lemoine NR, Williams GT, Williams ED and Wynford-Thomas D, 1988, Ha-ras restriction fragment length polymorphism in colorectal cancer. Br J Cancer, 57, 135–8.
Knyazev PG, Nikiforova IF, Serova OM and Pluznikova GF, 1990, Distribution and rearrangement of alleles of c-Ha-ras-1 protooncogene and their correlation with the development of lung, ovarian and thyroid cancers. Neoplasma, 37, 647–55.
Gerhard DS, Drocopoli NC, Bale SJ, et al. 1987, Evidence against Ha-ras-1 involvement in sporadic and familial melanoma. Nature, 325, 73–5.
Ishikawa J, Maeda S, Takahashi R, Kamidono S and Sigiama T, 1987, Lack of correlation between rare Ha-ras alleles and urothelial cancer in Japan. Int J Cancer, 40, 474–8.
Kakehi Y and Yoshida O, 1989, Restriction fragment length polymorphism of the L-myc gene and susceptibility to metastasis in renal cancer patients. Int J Cancer, 43, 391–4.
Ikeda I, Ishizaka Y, Ochiai M, et al. 1988, No correlation between L-myc restriction fragment length polymorphism and malignancy of human colorectal cancer. Jap J Cancer Res, 79, 674–6.
Mironov NM, Aguelon A-M, Potapova GI, Gorbunov OV, Klimenkov AA and Yamasaki H, 1994, L-myc allele polymorphism and prognosis for metastases in Russian gastric cancer patients. Eur J Cancer, 30, 1732.
Kawashima K, Shikama H, Imoto K, et al. 1988, Close correlation between restriction fragment length polymorphism of the L-myc gene and metastasis of human lung cancer to the lymph nodes and other organs. Proc Natl Acad Sci USA, 85, 2353–6.
Weston A, Caporaso NE, Perrin LS, et al. 1992, Relationship of H-ras-1, L-myc and p53 polymorphism with lung cancer risk and prognosis. Envir Hlth Perspect, 98, 61–7.
Redondo M, Concha A, Oldiviera R, et al. 1991, Expression of HLA class I and II antigens in bronchogenic carcinomas: its relationship to cellular DNA content and clinical-pathological parameters. Cancer Res, 51, 4948–54.
Wrba F, Ritzinger E, Reiner A and Holzner JH, 1986, Transferrin receptor (TrfR) expression in breast carcinoma and its possible relationship to prognosis. Virchows Arch (Pathol Anat), 410, 69–73.
Robbins BA, Vega D, Ogata K, Tan EM and Nakamura RM, 1987, Immunohistochemical detection of proliferating cell nuclear antigen in solid human malignancies. Arch Pathol Lab Med, 111, 841–5.
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Zborovskaya, I., Gasparian, A., Kitaeva, M. et al. Simultaneous detection of genetic and immunological markers in non-small cell lung cancer: prediction of metastatic potential of tumor. Clin Exp Metast 14, 490–500 (1996). https://doi.org/10.1007/BF00115109
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DOI: https://doi.org/10.1007/BF00115109