Abstract
The formation of new blood vessels is essential for tumor growth and progression. Until today there are only few studies of the immunohistochemical assessment of angiogenesis in gastric cancer by the evaluation of the expression of CD34 antigen. The aim of this study was to analyze the relationship between microvessel density (MVD) expressed as the mean count of CD34 immunostained vessels and clinicopathologic features of gastric tumors (the histological type according to the Lauren classification, tumor grade - G; presence of lymph node metastases - N; depth of tumor invasion; stage of disease (UICC-AJCC 1988–1992), p53 expression, tumor cell proliferative activity described as the Ki67 labelling index and apoptotic index of tumor cells - TUNEL method). We assessed formalin-fixed, paraffin-embedded tissue samples obtained during potentially radical gastrectomy from 58 patients with primary gastric adenocarcinoma. The representative tissue blocks from each tumor were used for the immunohistochemical assay and examined by two pathologists independently. MVD was counted in five tumor areas of the most intensive neovascularization (x 200 field by light microscopy) and the mean counts were recorded. The mean MVD (CD34 expression value ± SD) in this study was 43,15 ± 19,8 per x 200 field. The study demonstrated the statistically significant correlation between MVD and two main histological parameters: tumor grading (p < 0.001) and tumor histological type according to Lauren’s classification (p<0.05). In well - and moderately - differentiated tumors (G1/2) MVD was significantly lower in comparison to the group of poorly differentiated cancer - G3 (mean value: 31,62 vs. 49,89). MVD was higher in diffuse type of gastric cancer comparing to intestinal type (50.05 ± 19,03 vs. 39.17 ±20,09). However, the authors failed to find a significant correlation between MVD and other investigated histopathological features in malignant gastric tumors. The close relationship between CD34 immunostaining, gastric cancer tumor vascularity and main histological parameters was shown in this study. It can be stated that analysis of expression of angiogenesis in gastric cancer may be helpful for better estimation of hematogenous recurrence and the selection of the group of patients for adjuvant antiangiogenic treatment.
Similar content being viewed by others
References
Roder JD, Bottcher K, Siewert JR, et al: Prognostic factors in gastric carcinoma. Results of the German Gastric Carcinoma Study 1992. Cancer 72:2089–97, 1993.
Folkman J: What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82:4–6, 1990.
Hansen S, Grabau DA, Sorensen FB, et al: Vascular grading of angiogenesis; prognostic significance in breast cancer. Br J Cancer 82:339–347, 2000.
Matsuyama K, Chiba Y, Sasaki M, et al: Tumor angiogenesis as a prognostic marker in operable non-small cell lung cancer. Ann Thorac Surg 65:1405–1409, 1998.
Chung YS, Maeda K, Sowa M: Prognostic value of angiogenesis in gastrointestinal tumors. Eur J Cancer 32A:2501–2505, 1996.
Schlingemann RO, Rietveld FJR, de Waal RMW et al: Leukocyte antigen CD34 is expressed by a subset of cultured endothelial cells and on endothelial abluminal microprocesses in the tumor stroma. Lab Invest 62:690–696, 1990.
Lauren P: The two main types of gastric carcinoma: diffuse and so-called intestinal type carcinoma Acta Pathol Microbiol Scand 64:31–49, 1965.
Rutkowski P, Jesionek-Kupnicka D, Tenderenda M: A study on the relationship between Ki67 labelling index and selected clinicopathological features in gastric cancer. Onkol Pol 2:143–146, 1999.
Weidner N, Semple JP, Weich WR, et al: Tumor angiogenesis and metastasis - correlation in invasive breast carcinoma. N Engl J Med 324:1–8, 1991.
Vermeulen PB, Gasparini G, Fox SB, et al: Quantification of angiogenesis in solid human tumors: an international consensus on the methodology and criteria of evaluation. Eur J Cancer 32A:2474–2484, 1996.
Banner BF, Whitehouse R, Baker SP, et al: Tumor angiogenesis in stage II colorectal carcinoma. Association with survival. Am J Clin Pathol 109:733–737, 1998.
Tanigawa N, Amaya H, Matsamura M, et al: Extent of tumor vascularization correlates with prognosis and hematogenous metastasis in gastric carcinomas. Cancer Res 56:2671–2676, 1996.
Kitadai Y, Haruma K, Sumii K, et al: Expression of interleukin-8 correlates with vascularity in human gastric carcinomas. Am J Pathol 152:93–96, 1998.
Inoue K, Ozeki Y, Suganuma T, et al: Vascular Endothelial Growth Factor Expression in Primary Esophageal Squamous Cell Carcinoma. Cancer 79:206–213, 1997.
Tanigawa N, Amaya H, Matsumura M, et al: Correlation Between Expression of Vascular Endothelial growth Factor and Tumor Vascularity and Patients Outcome in Human Gastric Carcinoma. J Clin Oncol 15:826–832, 1997.
Ikeguchi M, Oka S, Saito H, et al: The expression of vascular growth factor and proliferative activity of cancer cells in gastric cancer. Langebecks Arch Surg 384:264–270, 1999.
Heimburg S, Oehler MK, Papadopoulos T, et al: Prognostic relevance of the endothelial marker CD 34 in ovarian cancer. Anticancer Res 19:2527–2529, 1999.
Engel CJ, Bennett ST, Chambers AF, et al: Tumor angiogenesis predicts recurrence in invasive colorectal cancer when controlled for Dukes stage. Am J Surg Pathol 20:1260–1265, 1996.
Setala LP, Kosma V-M, Marin S, et al: Prognostic factors in gastric cancer; the value of vascular invasion, mitotic rate and lymphoplasmatic infiltration. Br J Cancer 74:766–772, 1996.
Gabbert HE, Meier S, Gerharz CD, et al: Tumor-cell dissociation at the invasive front: a new prognostic parameter in gastric cancer patients Int J Cancer 50:202–207, 1992
Rak J, Filmus J, Kerbel RS: Reciprocal paracrine interactions between tumor cells endothelial cells: the “angogenesis progression” hypothesis. Eur J Cancer 32A:2438–2450, 1996
Dvorak HF, Siossat TM, Brown LF, et al: Distribution of vascular permeability factors in tumors: concentration in tumor blood vessels. J Exp Med 174:1275–1278, 1991
Connolly DT, Heuvelman DM, Nelson R, et al: Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest 84:1470–1478, 1989.
Haraguchi M, Miyadera K, Uemura K, et al: Angiogenic activity of enzymes. Nature (Lond.) 368:198, 1994.
Bussolino F, Albini A, Camussi G, et al: Role of soluble mediators in angiogenesis. Eur J Cancer 32A, 2401–2412, 1996.
Maeda K, Kang S-M, Ogawa M, et al: Combined analysis of vascular endothelial growth factors and platelet-derived endothelial cell growth factor expression in gastric carcinoma. Int J Cancer (Pred Oncol) 74:545–550, 1997.
Pritchard AJ, Chatterjee T, Wilkinson M, et al: Evidence for weak angogenic response to human colorectal cancer. Br J Cancer 71:1081–1086, 1995.
Ohtani H, Sasano N: Stromal cell changes in human colorectal adenomas and carcinomas. Virchows Arch A Pathol Anat Histopathol 401:209–222, 1983.
Nakayama H, Enzan H, Miyazaki E, et al: Differential expression of CD34 in normal colorectal tissue, peritumoral inflammatory tissue, and tumor stroma. J Clin Pathol 53:626–629, 2000.
Ikeguchi M, Cai J, Yamane N, et al: Clinical significance oif spontaneous apoptosis in advanced gastric adenocarcinoma Cancer 85:2329–2323, 1999.
Tu C, Tanigawa N: Spontaneous Apoptosis is Inversely Related to Intratumoral Density in Gastric Carcinoma Cancer Res 57:221–224, 1997.
Rosa JC, Mendes R, Filipe MI, et al: Measurement of cell proliferation in gastric carcinoma; comparative analysis of Ki67 and proliferative cell nuclear antigen (PCNA) Histochem J 24:93–101, 1992.
Kirsch D, Kastan M: Tumor-suppressor p53; implications for tumor development and prognosis. J Clin Oncol 1998; 16:3158–3168, 1998.
Tanigawa N, Amaya H, Matsumura M, Shimomatsuya T: Association of tumor vasculature with tumor progression overall survival of patients with non-early gastric carcinomas Br J Cancer 75:556–571, 1997.
Tanigawa N, Amaya H, Matsumura M, et al: Tumor angiogenesis and mode of metastasis in patients with colorectal cancer Cancer Res 57:1043–1046, 1997.
Author information
Authors and Affiliations
Corresponding author
Additional information
This study was supported by the grant No 502-11-397 from Medical University of Lodz, Poland
Rights and permissions
About this article
Cite this article
Tenderenda, M., Rutkowski, P., Jesionek-Kupnicka, D. et al. Expression of CD34 in gastric cancer and its correlation with histology, stage, proliferation activity, p53 expression and apoptotic index. Pathol. Oncol. Res. 7, 129–134 (2001). https://doi.org/10.1007/BF03032579
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03032579