Abstract
E‐Selectin is an inducible adhesion molecule, which is expressed on cytokine‐activated endothelial cells and is thought to interact with cancer cells to initiate metastases. The relationship between serum E‐selectin levels and prognoses in 101 patients with resected non‐small cell lung cancers (NSCLCs) was studied, and survival curves were compared in relation to E‐selectin levels and expression of two carbohydrate antigens, Sialyl Lewisx (SLX) and Sialyl Lewisa (CA19‐9), which were immunohistochemically detected in resected specimens in 65 of the 101 cases. The serum Eselectin level on admission was 48.9±25.7 ng/ml (mean±SD, n=101), and the E‐selectin‐positive rate was 22.7%, being correlated with the progression of T‐factor. The high E‐selectin group showed a significantly worse survival rate than the normal E‐selectin group. Multivariate analysis confirmed the significant prognostic value of E‐selectin. The mean postoperative E‐selectin level in 52 cases (36.93 ng/ml) was significantly lower than the preoperative E‐selectin level (43.57 ng/ml), indicating that certain NSCLCs might induce the expression of E‐selectin. In cases expressing carbohydrate antigens (SLX, CA19‐9), the high E‐selectin group showed a significantly worse survival curve than the normal E‐selectin group. On the other hand, there was no significant difference in the survival curve between the high and normal E‐selectin groups when carbohydrate antigens were negative. These results suggest that patients who have high serum E‐selectin levels, especially with carbohydrate antigen‐positive NSCLC, might be expected to have poor prognoses.
Keywords: Lung cancer, Adhesion molecule, Carbohydrate antigen, Prognosis, Surgical resection
Full Text
The Full Text of this article is available as a PDF (82.0 KB).
REFERENCES
- 1).Bevilacqua , M. P. , Pober , J. S. , Mendrick , D. L. , Cotran , R. S. and Gimbrone , M. J.Identification of an inducible endothelial‐leukocyte adhesion molecule . Proc. Natl. Acad. Sci. USA , 84 , 9238 – 9242 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2).Kannagi , R. , Fukushi , Y. , Tachikawa , T. , Noda , A. , Shin , S. , Shigeta , K. , Hiraiwa , N. , Fukuda , Y. , Inamoto , T. , Hakomori , S. and Imura , H.Quantitative and qualitative characterization of cancer‐associated serum glycoprotein antigens expressing fucosyl or sialosyl‐fucosyl type 2 chain polylactosamine . Cancer Res. , 46 , 2619 – 2626 ( 1986. ). [PubMed] [Google Scholar]
- 3).Koprowski , H. , Steplewski , Z. and Mitchell , K.Colorectal carcinoma antigens detected by hybridoma antibodies . Somatic Cell Genet. , 5 , 957 – 962 ( 1979. ). [DOI] [PubMed] [Google Scholar]
- 4).Hakomori , S.Aberrant glycosylation in cancer cell membranes as focused on glycolipids: overview and perspectives . Cancer Res. , 45 , 2405 – 2414 ( 1985. ). [PubMed] [Google Scholar]
- 5).Japan Lung Cancer Society. “ General Rule for Clinical and Pathological Record of Lung Cancer” , 4th Ed. ( 1995. ) Kanehara Co. , Tokyo ( in Japanese ). [Google Scholar]
- 6).Bevilacqua , M. P. , Stengelin , S. , Gimbrone , M. J. and Seed , B.Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins . Science , 243 , 1160 – 1165 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 7).Phillips , M. L. , Nudelman , E. , Gaeta , F. C. , Perez , M. , Singhal , A. K. , Hakomori , S. and Paulson , J. C.ELAM‐1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl‐Lex . Science , 250 , 1130 – 1132 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 8).Takada , A. , Ohmori , K. , Takahashi , N. , Tsuyuoka , K. , Yago , A. , Zenita , K. , Hasegawa , A. and Kannagi , R.Adhesion of human cancer cells to vascular endothelium mediated by a carbohydrate antigen, sialyl Lewis A . Biochem. Biophys. Res. Commun. , 179 , 713 – 719 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 9).Kimura , S. , Saitou , D. , Kimura , K. , Yakata , M. and Hakomori , S.Pathological study of carbohydrate antigens in human lung cancer with monoclonal antibodies . Jpn. J. Clin. Pathol. , 39 , 765 – 772 ( 1991. ). ( in Japanese ). [PubMed] [Google Scholar]
- 10).Nakamori , S. , Kameyama , M. , Imaoka , S. , Furukawa , H. , Ishikawa , O. , Sasaki , Y. , Izumi , Y. and Irimura , T.Involvement of carbohydrate antigen sialyl Lewisx in colorectal cancer metastasis . Dis. Colon Rectum , 40 , 420 – 431 ( 1997. ). [DOI] [PubMed] [Google Scholar]
- 11).Mitsuoka , C. and Kannagi , R.Clinical significance of circulating soluble E‐selectin (ELAM‐1) in patients with cancers . Jpn. J. Clin. Med. , 53 , 1770 – 1775 ( 1995. ). ( in Japanese ). [PubMed] [Google Scholar]
- 12).Takada , A. , Ohmori , K. , Yoneda , T. , Tsuyuoka , K. , Hasegawa , A. , Kiso , M. and Kannagi , R.Contribution of carbohydrate antigens sialyl Lewis A and sialyl Lewis X to adhesion of human cancer cells to vascular endothelium . Cancer Res. , 53 , 354 – 361 ( 1993. ). [PubMed] [Google Scholar]
- 13).Banks , R. E. , Gearing , A. J. , Hemingway , I. K. , Norfolk , D. R. , Perren , T. J. and Selby , P. J.Circulating intercellular adhesion molecule‐1 (ICAM‐1), E‐selectin and vascular cell adhesion molecule‐1 (VCAM‐1) in human malignancies . Br. J. Cancer , 68 , 122 – 124 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14).Matsuura , N. , Narita , T. , Mitsuoka , C. , Kimura , N. , Kannagi , R. , Imai , T. , Funahashi , H. and Takagi , H.Increased concentration of soluble E‐selectin in the sera of breast cancer patients . Anticancer Res. , 17 , 1367 – 1372 ( 1997. ). [PubMed] [Google Scholar]
- 15).Fukushima , K.Expression of Lewisx, sialylated Lewisx, Lewisa and sialylated Lewisa antigens in human lung carcinoma . Tohoku J. Exp. Med. , 163 , 17 – 30 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 16).Matsumoto , H. , Muramatsu , H. , Muramatsu , T. and Shimazu , H.Carbohydrate profiles shown by a lectin and a monoclonal antibody correlate with metastatic potential and prognosis of human lung carcinomas . Cancer , 69 , 2084 – 2090 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 17).Ogawa , J. , Tsurumi , T. , Yamada , S. , Koide , S. and Shohtsu , A.Blood vessel invasion and expression of Sialyl Lewisx and proliferating cell nuclear antigen in stage I nonsmall cell lung cancer. Relation to postoperative recurrence . Cancer , 73 , 1177 – 1183 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 18).Kawai , T. , Suzuki , M. , Kase , K. and Ozeki , Y.Expression of carbohydrate antigens in human pulmonary adenocarcinoma . Cancer , 72 , 1581 – 1587 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 19).Wamil , B. D. , Thurman , G. B. , Sundell , H. W. , DeVore , R. F. , Wakefield , G. , Johnson , D. H. , Wang , Y. F. and Hellerqvist , C. G.Soluble E‐selectin in cancer patients as a marker of the therapeutic efficacy of CM101, a tumor‐inhibiting anti‐neovascularization agent, evaluated in phase I clinical trial . J. Cancer Res. Clin. Oncol. , 123 , 173 – 179 ( 1997. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
