ZNF217 and FGFR1 Amplification in the Progression of In Situ to Invasive Breast Carcinoma
Minhye Jang, Eun Joo Kim, Yoomi Choi, Hee Eun Lee, So Yeon Park. Seoul National University College of Medicine, Seoul, Republic of Korea; Seoul National University Hospital, Seoul, Republic of Korea; Seoul National University Bundang Hospital, Seongnam, Republic of Korea
Background: Gene amplification is an important mechanism for activation of oncogene in malignant tumors. Although amplification of HER2, C-MYC, CCND1, FGFR1 and ZNF217 has been described in breast cancers, their role in the progression of in situ to invasive breast carcinoma has been rarely studied. To investigate their role in the progression of breast cancer, we compared the amplification frequency of these genes in pure ductal carcinoma in situ (DCIS), DCIS associated with invasive carcinoma and invasive carcinoma.
Design: We performed fluorescence in situ hybridization of the selected genes on tissue microarrays composed of 175 pure DCIS and 208 DCIS associated with invasive carcinoma and 427 invasive carcinomas. For the cases of DCIS associated with invasive carcinoma, we compared gene amplification status of intraductal and invasive components in the individual patients.
Results: Amplification rate of ZNF217 and FGFR1 was significantly higher in invasive carcinoma than in pure DCIS (ZNF217, 9.4% vs. 3.5%, p=0.015; FGFR1, 11.8% vs. 6.0%, p=0.035). On the contrary, HER2 gene amplification was more frequently found in pure DCIS compared to invasive carcinoma (20.0% vs. 31.4 %, p=0.002). ZNF217 amplification rate was also significantly higher in DCIS associated with invasive carcinoma than in pure DCIS (ZNF217, 11.9% vs. 3.5%, p=0.003). Overall, gene amplification frequency of all genes in invasive carcinoma and DCIS associated with invasive carcinoma did no differ significantly. Comparing matched invasive and DCIS components in 208 cases, HER2, C-MYC, CCND1, and ZNF217 amplification status was concordant in most cases. However, FGFR1 amplification was increased in the invasive component (p=0.031). In survival analyses, FGFR1 amplification was associated with decreased disease free survival in the patients with invasive carcinoma (p=0.003).
Conclusions: Our study revealed that DCIS associated with invasive carcinoma is similar to invasive carcinoma in terms of gene amplification of analyzed genes. However, our data also showed significant difference of ZNF217 and FGFR1 amplification between pure DCIS and invasive carcinoma and FGFR1 amplification between invasive and DCIS components of the same tumor, and the association of FGFR1 amplification with patients' prognosis, suggesting the role of ZNF217 and FGFR1 amplification in the breast cancer progression including tumor invasion.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 34, Tuesday Morning