Cancer Letters

Cancer Letters

Volume 176, Issue 1, 8 February 2002, Pages 111-118
Cancer Letters

Prognostic significance of microvessel density, vascular cuffing and vascular endothelial growth factor expression in ovarian carcinoma: a special review for clear cell adenocarcinoma

https://doi.org/10.1016/S0304-3835(01)00754-6Get rights and content

Abstract

Our purpose is to demonstrate the relationship between microvessel density (MVD), vascular cuffing (VC), vascular endothelial growth factor (VEGF) expression and clinicopathological parameters in ovarian cancer. Surgical specimens from 105 primary ovarian cancers were examined for vascularization and VEGF expression by immunohistochemical staining. The higher MVD group (MVD≧70) and the positive VEGF group were associated with better progression-free survival only in early stages. The significant association of the MVD with better progression-free survival was recognized only in the patients with clear cell adenocarcinomas. The complete VC group showed a similar trend as MVD though there was no statistical difference. A multivariate analysis revealed MVD to correlate independently with progression-free survival. In ovarian carcinoma, MVD was found to be an independent prognostic factor. In addition, the higher MVD with clear cell adenocarcinoma had the better prognosis. The clinicopathological role of angiogenesis should be analyzed taking account of histologic type.

Introduction

Angiogenesis is essential for tumor growth and metastasis. Folkman showed that tumor growth, after reaching the size of about 1–2 mm2, is strictly dependent on angiogenesis [1]. The evidence that angiogenesis, quantitated by microvessel counting, could be related to metastases and patient survival was shown in several tumors, including breast [2], lung [3], head and neck [4], prostate [5] and testis [6]. Furthermore, in a follow-up study, Weidner has found that microvessel density (MVD) in the area of most intense neovascularization in invasive breast carcinoma is an independent, highly significant, and accurate prognostic indicator in predicting overall and relapse-free survival in patients with early stage breast carcinoma [7]. We reported that MVD had an association with prognosis in endometrium [8] and uterine cervical adenocarcinomas [9].

We also demonstrated that epithelial-stromal vascular cuffing (VC), a bead-like arrangement of microvessels closely surrounding microscopic tumor nests, correlates with a significantly worse prognosis in squamous cell carcinoma of the uterine cervix.

Vascular endothelial growth factor (VEGF) is a multifunctional glycoprotein cytokine that potently stimulates angiogenesis in vivo [10]. Among several angiogenic factors, VEGF is thought to be one of the most important factors for tumor angiogenesis [11], [12]. VEGF has been observed in a variety of tumor cell lines and in many types of human solid tumors [13], [14], [15], [16], [17].

In ovarian carcinoma, however, the clinicopathologic role of angiogenesis is as yet unknown. While some authors presented a significant association of microvessel counts with prognosis in ovarian carcinoma, others did not.

This report presents MVD, VC and VEGF expression and their correlation with prognosis in epithelial ovarian carcinoma taking into account the stage and the histologic type.

Section snippets

Patients

One hundred and five consecutive patients with primary ovarian carcinoma were initially treated with surgery at the Department of Gynecology and Obstetrics of Kyushu University Hospital from 1980 to 1995. Patients with borderline epithelial ovarian carcinoma and primary peritoneal carcinoma were excluded. Initial surgery was composed of abdominal hysterectomy, bilateral salpingo-oophorectomy, paraaortic lymph node biopsy, omentectomy and appendectomy. Since 1986, dissection of the pelvic lymph

Results

Patient ages ranged from 25 to 77 years (median 52 years). The histologic types of tumors were as follows: 57 serous adenocarcinomas, 22 clear cell carcinomas, 17 mucinous adenocarcinomas, and nine endometrioid adenocarcinomas (Table 1).

The median MVD was 77 microvessels/high power field (range 21–244). Fig. 2a,d shows the relationship between MVD and progression-free survival. The MVD≧70 was associated with better progression-free survival in early stages (stages I–II) (log-rank, P=0.003). In

Discussion

In ovarian carcinoma, the clinicopathologic role of angiogenesis is as yet unknown. Some authors have found no significant relationship between MVD and survival [19], [20], [21]. Van Diest reported that MVD had no association with prognosis, stage, tumor grade and DNA ploidy in advanced ovarian carcinoma. Abulafia and Nakanishi similarly found that MVD was not correlated with patient survival.

On the other hand, others have found that high MVD correlated with a worse prognosis; however, MVD did

Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technolgy (Nos. 11671626, 12671612, 12671613).

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