Relationship between Matrix Metalloproteinase (MMP)-2, 9 Expressions and VEGF Expression and Microvessel Density in Ductal Carcinoma in Situ of the Breast

Park, Ju Sang; Jung, Soo Gin; Kim, Tae Hyun; Lee, Jin Yong; Yoon, Hye Kyong

Abstract

PURPOSE
MMPs are involved in the degradation of the extracellular matrix, which is an important step in tumor invasion and metastasis. Among the MMPs, a positive correlation between the expressions of MMP-2 and MMP-9, and the aggressive behavior of breast carcinomas has been reported, but the role of the MMP-2 and MMP-9 expressions in DCIS is still not known. Angiogenesis has a crucial role in tumor growth and metastasis. The aim of this study was to investigate the relationships between the expressions of the MMPs, the angiogenic factor (VEGF) and the microvessel density (MVD) in a ductal carcinoma in situ (DCIS) of the breast. METHODS: 42 cases of DCIS, diagnosed at the Busan Paik Hospital, between 1992 and 2002, were the subjects of this study. The rates of MMP-2 and 9 expressions and VEGF were evaluated using immunohistochemistry, and the MVD was measured by CD 34 immunohistochemical staining. The statistical analyses between the expressions of MMP-2, MMP-9 and VEGF and the MVD, patient's age (more than 50 years old, less than 50 years old), histological subtype (comedo or non-comedo) and nuclear grade (I, II, III), and their correlation were exained. RESULTS: The expressions of MMP-2 and MMP-9 were noted in 20 (47.6%) and 22 (52.4%) of the 42 cases, respectively. There were no significant relationships between the expressions of MMP-2 and MMP-9 and the patient's age and histological subtype, but the expression rate of MMP-9 showed an increased tendency in cases with nuclear grades II and III compared with the cases with nuclear grade I (P=0.0863), but no significant difference between the MMP-2 expression and the nuclear grades was noted. The VEGF was expressed in 47.6% of the cases, and the mean MVD was 21 per x200 field, with 13 (30.9%) of the 42 cases showing increased MVD. The VEGF expression rate showed an increasing tendency in the cases younger than 50 years old (P= 0.1011), but no significant differences according to the histological subtype and nuclear grades were seen. There were no relationships between the MVD and the clinico-pathological factors. The MVD showed an increasing tendency in cases with a non-comedo histological type compared to the comedo type (P=0.0536). No positive correlation between the expression of VEGF and MVD was noted. No significant relationship between expressions of MMP-2 and VEGF and the MVD were seen, but the rate of MMP-9 expression was significantly higher in the VEGFpositive cases (P=0.0293), however, no relationship between MMP9 expression and MVD was found. CONCLUSION: The expressions of MMP-2 and MMP-9 in DCIS are suggestive of their involvement in the development of breast cancers. However, with non-invasive lesions, and the positive correlation between the MMP-9 and VEGF expressions and the nuclear grades, means that the expression of MMP-9 may represent the biological behavior of DCIS, but the role of MMP-2 expression is still uncertain in the development of breast carcinomas.