Academic journal article Iranian Journal of Public Health

Prognostic Significance of VEGF-C Expression in Patients with Breast Cancer: A Meta-Analysis

Academic journal article Iranian Journal of Public Health

Prognostic Significance of VEGF-C Expression in Patients with Breast Cancer: A Meta-Analysis

Article excerpt


Breast cancer is the leading cause of cancer mor- tality in women worldwide and is one of the major contributors to the global health burden (1-3). Mounting clinical data suggest that the develop- ment of metastatic spread of the disease is respon- sible for at least 90% of the cancer-associated mortality, and the survival rate falls from 90% for localized breast cancer to 20% for metastatic breast cancer (4). Lymphatic metastasis is one of the most important pathways of breast cancer sys- temic metastasis, and is closely related to progno- sis and therapy plans for breast cancer patients. Frequently, the initial sites of metastasis are the regional lymph nodes (5, 6), and migration of tu- mor cells into the lymph nodes is greatly facili- tated by lymphangiogenesis, a process that gener- ates new lymphatic vessels from pre-existing lym- phatics or lymphatic endothelial progenitors (7-9). Some researchers suggest that the vascular endo- thelial growth factor-C (VEGF-C)/ vascular en- dothelial growth factor receptor 3 (VEGFR3) sig- naling system is the most efficient pathway in reg- ulating lymphangiogenesis. VEGF-C, also called lymphatic vessel growth factor, belongs to the VEGF family, and involves in tumor lymph- angiogenesis by inducing lymphatic endothelial proliferation and vessel enlargement to facilitate the shedding of tumor cells into the surrounding lymphatic vessels (10, 11). VEGF-C expression has recently been reported to be correlated with lymph node metastasis in breast (12, 13), gastric (14), colorectal (15), lung (16), prostate (17), head and neck (18), and gallbladder cancer (19). How- ever, in breast cancer, the definite role of VEGF- C has not yet been elucidated. Some studies re- ported that VEGF-C expression correlated with lymph node metastasis and patients' poor survival (13, 20), while some others not (21, 22). To date, insufficient samples and some other factors have resulted in controversial results of different clini- cal studies.

To derive a more precise estimation of the rela- tionship between VEGF-C expression and clinical outcomes in patients with breast cancer, we per- formed a meta-analysis of 14 prospective or retro- spective cohort studies with a total of 1,573 breast cancer patients.


Search strategy and selection criteria

A systematic literature search of MEDLINE (1960 through February, 2013), EMBASE (1988 through February, 2013), web of Science (1960 through February, 2013) databases, and two Chi- nese databases (Wanfang and Chinese National Knowledge Infrastructure databases, 1960 through February, 2013) was conducted by two study investigators (D.C. and B.L.) independently for all relevant articles about the prognostic value of VEGF-C expression in breast cancer patients. Key words used in the research included "VEGF- C", "breast cancer", "immunohistochemistry", "breast neoplasma(s)", "breast carcinoma", "me- tastasis", and "prognosis". Studies eligible for in- clusion in this meta-analysis should meet the fol- lowing criteria: 1) measures VEGF-C express-ion in the cancer tissue with immunohis-tochemistry (IHC), 2) patients have pathologically confirmed breast cancer, 3) patients provides information on survival time according to VEGF-C expression; 4) patients has a follow up time exceeding 5 years. When an individual author published several arti- cles obtained from the same patient population, only the newest or most complete article was in- cluded in the analysis. The exclusion criteria of the meta-analysis were: (a) animal studies; (b) meta- analyses, letters, reviews, meeting abstracts, or edi- torial comments; (c) studies with duplicate data or incomplete data.

Data abstraction

Two reviewers independently extracted the fol- lowing data from each study: first author's name, year of publication, type of cohort study, country of origin, total number of cases (N), follow-up time, and numbers of the patients with positive and negative expression of VEGF-C, etc. …

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