Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Dec;74(11):1783–1788. doi: 10.1038/bjc.1996.630

Expression of oncoproteins and the amount of eosinophilic and lymphocytic infiltrates can be used as prognostic factors in gastric cancer. Dutch Gastric Cancer Group (DGCG).

I Songun 1, C J van de Velde 1, J Hermans 1, S T Pals 1, H W Verspaget 1, A N Vis 1, A G Menon 1, S V Litvinov 1, J H van Krieken 1
PMCID: PMC2077204  PMID: 8956793

Abstract

Preoperative staging of gastric cancer is difficult. Several molecular markers associated with initiation and progression of cancer seem promising for obtaining preoperative prognostic information. To investigate whether these markers are indicative especially for the presence of lymph node metastases in patients with gastric cancer, we have examined primary tumour specimens from 105 patients with primary adenocarcinoma of the stomach entered in a surgical trial. In this trial, lymph node status was determined by strictly quality-controlled lymph node dissection and examination. The selected markers were growth regulators (p53, Rb and myc), metastasis-suppressor gene product (nm23), adhesion molecules (Ep-CAM, E-cadherin, CD44v5 and CD44v6) and urokinase-type plasminogen activator (u-PA). Also, the amount of eosinophilic and lymphocytic infiltrates available post-operatively was analysed with respect to its prognostic value for lymph node status. Moreover, the association of these parameters with survival and disease-free period (DFP) was evaluated. Of all molecular markers investigated, only Rb expression had a significant association with the presence of lymph node metastasis in both univariate and multivariate analysis. For curative resectability, a significant association was found with Rb and E-cadherin expression, while in multivariate analysis Rb and myc were selected as the combination with additional independent prognostic value, and E-cadherin had no additional independent value. For overall survival in univariate analysis, the amount of both eosinophilic and lymphocytic infiltrates and Rb and myc expression were of significant prognostic value. Only the amount of lymphocytic infiltrate had a prognostic significance for DFP. In stepwise multivariate analysis, TNM stage (I + II) and marked lymphocytic infiltrate were associated with better overall survival and longer DFP. We conclude that, if these results are confirmed in a larger series of patients, molecular markers can provide useful prognostic information.

Full text

PDF
1783

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akoh J. A., Sedgwick D. M., Macintyre I. M. Improving results in the treatment of gastric cancer: an 11-year audit. Br J Surg. 1991 Mar;78(3):349–351. doi: 10.1002/bjs.1800780325. [DOI] [PubMed] [Google Scholar]
  2. Allum W. H., Powell D. J., McConkey C. C., Fielding J. W. Gastric cancer: a 25-year review. Br J Surg. 1989 Jun;76(6):535–540. doi: 10.1002/bjs.1800760604. [DOI] [PubMed] [Google Scholar]
  3. Auguste L. J., Masood S., Westerband A., Belluco C., Valderamma E., Attie J. Oncogene expression in follicular neoplasms of the thyroid. Am J Surg. 1992 Dec;164(6):592–593. doi: 10.1016/s0002-9610(05)80713-5. [DOI] [PubMed] [Google Scholar]
  4. Bonenkamp J. J., Songun I., Hermans J., Sasako M., Welvaart K., Plukker J. T., van Elk P., Obertop H., Gouma D. J., Taat C. W. Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet. 1995 Mar 25;345(8952):745–748. doi: 10.1016/s0140-6736(95)90637-1. [DOI] [PubMed] [Google Scholar]
  5. Bonenkamp J. J., Songun I., Hermans J., van de Velde C. J. Prognostic value of positive cytology findings from abdominal washings in patients with gastric cancer. Br J Surg. 1996 May;83(5):672–674. doi: 10.1002/bjs.1800830526. [DOI] [PubMed] [Google Scholar]
  6. Borg A., Baldetorp B., Fernö M., Olsson H., Sigurdsson H. c-myc amplification is an independent prognostic factor in postmenopausal breast cancer. Int J Cancer. 1992 Jul 9;51(5):687–691. doi: 10.1002/ijc.2910510504. [DOI] [PubMed] [Google Scholar]
  7. Bártek J., Vojtesek B., Grand R. J., Gallimore P. H., Lane D. P. Cellular localization and T antigen binding of the retinoblastoma protein. Oncogene. 1992 Jan;7(1):101–108. [PubMed] [Google Scholar]
  8. Cordon-Cardo C., Wartinger D., Petrylak D., Dalbagni G., Fair W. R., Fuks Z., Reuter V. E. Altered expression of the retinoblastoma gene product: prognostic indicator in bladder cancer. J Natl Cancer Inst. 1992 Aug 19;84(16):1251–1256. doi: 10.1093/jnci/84.16.1251. [DOI] [PubMed] [Google Scholar]
  9. Cryns V. L., Thor A., Xu H. J., Hu S. X., Wierman M. E., Vickery A. L., Jr, Benedict W. F., Arnold A. Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma. N Engl J Med. 1994 Mar 17;330(11):757–761. doi: 10.1056/NEJM199403173301105. [DOI] [PubMed] [Google Scholar]
  10. Fox S. B., Persad R. A., Royds J., Kore R. N., Silcocks P. B., Collins C. C. p53 and c-myc expression in stage A1 prostatic adenocarcinoma: useful prognostic determinants? J Urol. 1993 Aug;150(2 Pt 1):490–494. doi: 10.1016/s0022-5347(17)35533-7. [DOI] [PubMed] [Google Scholar]
  11. Harbour J. W., Lai S. L., Whang-Peng J., Gazdar A. F., Minna J. D., Kaye F. J. Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science. 1988 Jul 15;241(4863):353–357. doi: 10.1126/science.2838909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Heider K. H., Dämmrich J., Skroch-Angel P., Müller-Hermelink H. K., Vollmers H. P., Herrlich P., Ponta H. Differential expression of CD44 splice variants in intestinal- and diffuse-type human gastric carcinomas and normal gastric mucosa. Cancer Res. 1993 Sep 15;53(18):4197–4203. [PubMed] [Google Scholar]
  13. Iwasaki K., Torisu M., Fujimura T. Malignant tumor and eosinophils. I. Prognostic significance in gastric cancer. Cancer. 1986 Sep 15;58(6):1321–1327. doi: 10.1002/1097-0142(19860915)58:6<1321::aid-cncr2820580623>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  14. Jass J. R. Lymphocytic infiltration and survival in rectal cancer. J Clin Pathol. 1986 Jun;39(6):585–589. doi: 10.1136/jcp.39.6.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mittnacht S., Weinberg R. A. G1/S phosphorylation of the retinoblastoma protein is associated with an altered affinity for the nuclear compartment. Cell. 1991 May 3;65(3):381–393. doi: 10.1016/0092-8674(91)90456-9. [DOI] [PubMed] [Google Scholar]
  16. Nekarda H., Schmitt M., Ulm K., Wenninger A., Vogelsang H., Becker K., Roder J. D., Fink U., Siewert J. R. Prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in completely resected gastric cancer. Cancer Res. 1994 Jun 1;54(11):2900–2907. [PubMed] [Google Scholar]
  17. Ninomiya I., Yonemura Y., Matsumoto H., Sugiyama K., Kamata T., Miwa K., Miyazaki I., Shiku H. Expression of c-myc gene product in gastric carcinoma. Oncology. 1991;48(2):149–153. doi: 10.1159/000226915. [DOI] [PubMed] [Google Scholar]
  18. Pietiläinen T., Lipponen P., Aaltomaa S., Eskelinen M., Kosma V. M., Syrjänen K. Expression of retinoblastoma gene protein (Rb) in breast cancer as related to established prognostic factors and survival. Eur J Cancer. 1995;31A(3):329–333. doi: 10.1016/0959-8049(94)00463-f. [DOI] [PubMed] [Google Scholar]
  19. Pretlow T. P., Keith E. F., Cryar A. K., Bartolucci A. A., Pitts A. M., Pretlow T. G., 2nd, Kimball P. M., Boohaker E. A. Eosinophil infiltration of human colonic carcinomas as a prognostic indicator. Cancer Res. 1983 Jun;43(6):2997–3000. [PubMed] [Google Scholar]
  20. Wanebo H. J., Kennedy B. J., Chmiel J., Steele G., Jr, Winchester D., Osteen R. Cancer of the stomach. A patient care study by the American College of Surgeons. Ann Surg. 1993 Nov;218(5):583–592. doi: 10.1097/00000658-199321850-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wyllie A. H. Apoptosis (the 1992 Frank Rose Memorial Lecture). Br J Cancer. 1993 Feb;67(2):205–208. doi: 10.1038/bjc.1993.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Xu H. J., Hu S. X., Benedict W. F. Lack of nuclear RB protein staining in G0/middle G1 cells: correlation to changes in total RB protein level. Oncogene. 1991 Jul;6(7):1139–1146. [PubMed] [Google Scholar]
  23. Yu C. C., Levison D. A., Dunn J. A., Ward L. C., Demonakou M., Allum W. H., Hallisey M. T. Pathological prognostic factors in the second British Stomach Cancer Group trial of adjuvant therapy in resectable gastric cancer. Br J Cancer. 1995 May;71(5):1106–1110. doi: 10.1038/bjc.1995.214. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES