Abstract
Tumour growth depends on neovascularisation and tumour cell proliferation. Factor VIII-related antigen (F-VIII RA) localises to vascular endothelium. Expression of proliferating cell nuclear antigen (PCNA) is correlated with cell proliferation. We investigated the correlation between the expression of these antigens and prognosis in gastric carcinoma. A total of 108 specimens resected from patients with gastric carcinoma were investigated by staining with monoclonal antibodies against F-VIII RA and PCNA. Microvessel count (MVC; the mean number of microvessels in the five areas of highest vascular density at 200 x magnification) and PCNA labelling index (PCNA LI; percentage of positive cells in more than 500 tumour cells) were determined. The results showed that prognosis was significantly worse in patients who had a tumour with a high MVC (16 or greater) or a high PCNA LI (42% or greater) than in those patients who had a tumour with a low MVC (less than 16) or a low PCNA LI (less than 42%). Furthermore, MVC was significantly associated with the risk of hepatic recurrence. In conclusion, both MVC and PCNA LI may be good prognostic indicators in patients with gastric carcinoma.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bosari S., Lee A. K., DeLellis R. A., Wiley B. D., Heatley G. J., Silverman M. L. Microvessel quantitation and prognosis in invasive breast carcinoma. Hum Pathol. 1992 Jul;23(7):755–761. doi: 10.1016/0046-8177(92)90344-3. [DOI] [PubMed] [Google Scholar]
- Bouzubar N., Walker K. J., Griffiths K., Ellis I. O., Elston C. W., Robertson J. F., Blamey R. W., Nicholson R. I. Ki67 immunostaining in primary breast cancer: pathological and clinical associations. Br J Cancer. 1989 Jun;59(6):943–947. doi: 10.1038/bjc.1989.200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Folkman J. The role of angiogenesis in tumor growth. Semin Cancer Biol. 1992 Apr;3(2):65–71. [PubMed] [Google Scholar]
- Garcia R. L., Coltrera M. D., Gown A. M. Analysis of proliferative grade using anti-PCNA/cyclin monoclonal antibodies in fixed, embedded tissues. Comparison with flow cytometric analysis. Am J Pathol. 1989 Apr;134(4):733–739. [PMC free article] [PubMed] [Google Scholar]
- Gasparini G., Weidner N., Bevilacqua P., Maluta S., Dalla Palma P., Caffo O., Barbareschi M., Boracchi P., Marubini E., Pozza F. Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma. J Clin Oncol. 1994 Mar;12(3):454–466. doi: 10.1200/JCO.1994.12.3.454. [DOI] [PubMed] [Google Scholar]
- Ingber D., Fujita T., Kishimoto S., Sudo K., Kanamaru T., Brem H., Folkman J. Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature. 1990 Dec 6;348(6301):555–557. doi: 10.1038/348555a0. [DOI] [PubMed] [Google Scholar]
- Landberg G., Tan E. M., Roos G. Flow cytometric multiparameter analysis of proliferating cell nuclear antigen/cyclin and Ki-67 antigen: a new view of the cell cycle. Exp Cell Res. 1990 Mar;187(1):111–118. doi: 10.1016/0014-4827(90)90124-s. [DOI] [PubMed] [Google Scholar]
- Liotta L. A., Saidel M. G., Kleinerman J. The significance of hematogenous tumor cell clumps in the metastatic process. Cancer Res. 1976 Mar;36(3):889–894. [PubMed] [Google Scholar]
- Miwa K. Evaluation of the TNM classification of stomach cancer and proposal for its rational stage-grouping. Jpn J Clin Oncol. 1984 Sep;14(3):385–410. [PubMed] [Google Scholar]
- Nagy J. A., Brown L. F., Senger D. R., Lanir N., Van de Water L., Dvorak A. M., Dvorak H. F. Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition. Biochim Biophys Acta. 1989 Feb;948(3):305–326. doi: 10.1016/0304-419x(89)90004-8. [DOI] [PubMed] [Google Scholar]
- Sowa M., Yoshino H., Kato Y., Nishimura M., Kamino K., Umeyama K. An analysis of the DNA ploidy patterns of gastric cancer. Cancer. 1988 Oct 1;62(7):1325–1330. doi: 10.1002/1097-0142(19881001)62:7<1325::aid-cncr2820620714>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
- Toi M., Kashitani J., Tominaga T. Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma. Int J Cancer. 1993 Sep 30;55(3):371–374. doi: 10.1002/ijc.2910550305. [DOI] [PubMed] [Google Scholar]
- Weidner N., Carroll P. R., Flax J., Blumenfeld W., Folkman J. Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol. 1993 Aug;143(2):401–409. [PMC free article] [PubMed] [Google Scholar]
- Weidner N., Folkman J., Pozza F., Bevilacqua P., Allred E. N., Moore D. H., Meli S., Gasparini G. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst. 1992 Dec 16;84(24):1875–1887. doi: 10.1093/jnci/84.24.1875. [DOI] [PubMed] [Google Scholar]
- Wilson G. D., McNally N. J., Dunphy E., Kärcher H., Pfragner R. The labelling index of human and mouse tumours assessed by bromodeoxyuridine staining in vitro and in vivo and flow cytometry. Cytometry. 1985 Nov;6(6):641–647. doi: 10.1002/cyto.990060621. [DOI] [PubMed] [Google Scholar]
- Yamaoka M., Yamamoto T., Masaki T., Ikeyama S., Sudo K., Fujita T. Inhibition of tumor growth and metastasis of rodent tumors by the angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (TNP-470; AGM-1470). Cancer Res. 1993 Sep 15;53(18):4262–4267. [PubMed] [Google Scholar]
- Yonemura Y., Kimura H., Fushida S., Tugawa K., Nakai Y., Kaji M., Fonseca L., Yamaguchi A., Miyazaki I. Analysis of proliferative activity using anti-proliferating cell nuclear antigen antibody in gastric cancer tissue specimens obtained by endoscopic biopsy. Cancer. 1993 Apr 15;71(8):2448–2453. doi: 10.1002/1097-0142(19930415)71:8<2448::aid-cncr2820710804>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
- van Dierendonck J. H., Keijzer R., van de Velde C. J., Cornelisse C. J. Nuclear distribution of the Ki-67 antigen during the cell cycle: comparison with growth fraction in human breast cancer cells. Cancer Res. 1989 Jun 1;49(11):2999–3006. [PubMed] [Google Scholar]