Abstract
21102 Background: MKI67 and MMP1 mRNA, which might reflect the biological processes of tumor proliferation and matrix degradation, respectively, have been proposed as prognostic marker in invasive carcinoma of the breast. We compared the expression of both genes in invasive lobular versus invasive ductal carcinoma, which represent the most common histological breast cancer subtypes. Methods: MKI67 and MMP1 mRNA expression was determined by microarray analysis of fresh frozen tumor tissue of 118 patients with invasive ductal and 39 patients with invasive lobular carcinoma. We compared the distribution of these markers between both histological subtypes as well as within each subtype between tumors from patients with or without subsequent distant metastasis or local recurrence by two tailed Mann-Whitney test. Results: MKI67 as marker of proliferation and MMP1 as marker of matrix degradation were significantly elevated in invasive ducal versus lobular carcinomas (p = 0.023 and p < 0.0001, respectively). Furthermore, elevation of both markers were significantly associated with the occurrence of metastasis in ductal (p = 0.023 and p = 0.012) but not in lobular carcinomas (p = 0.986 and p = 0.366). In addition, no significant association was found between these markers and development of local recurrence in patients with ductal (p = 0.304 and p = 0.899) or lobular (p = 0.891 and p= 0.153) carcinomas . Conclusions: Our data suggest that differences exist between ductal and lobular carcinoma of the breast regarding both the expression and the prognostic impact of MKI67 and MMP1. Furthermore, the prognostic relevance of proliferation and matrix degradation was more important for the development of distant metastasis than for the development of local recurrence in ductal carcinoma emphasizing differences in the underlying biology of local recurrence and distant metastasis. No significant financial relationships to disclose.
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