Ubiquinol cytochrome c reductase (UQCRFS1) gene amplification in primary breast cancer core biopsy samples.

OBJECTIVES: The ubiquinol cytochrome c reductase UQCRFS1 is a key subunit of the cytochrome bc1 complex (complex III) of the mitochondrial respiratory chain. The purpose of this study is to evaluate the significance of the ubiquinol cytochrome c reductase UQCRFS1 gene amplification in primary breast cancers. METHODS: Samples were obtained from image-guided core needle biopsies (CNB) in 40 patients with nontreated breast cancers. To examine UQCRFS1 gene amplification, we employed fluorescent in situ hybridization using BACs RP11-46I12 that harbors UQCRFS1 gene, RP11-110J19 that overlaps to RP11-46I12, and CA125 as a control gene. The amplification data were evaluated blindly of histopathological factors. RESULTS: Amplification of UQCRFS1 gene was found in 5 of 39 specimens (12.8%). The specimens with amplified UQCRFS1 gene were associated with high grade of cancer cells (P = 0.005). CONCLUSIONS: These results suggest that the UQCRFS1 gene appears to be involved in development of more aggressive phenotype of breast cancer.

CA125 and UQCRFS1 FISH studies of ovarian carcinoma.

OBJECTIVE: With the gene CA125 having recently been cloned, we chose to investigate the gene copy number of various ovarian cancer samples by FISH. As a control we chose BACs close to the chromosome 19 centromere. One of these BACs carries the gene UQCRFS1. METHODS: We developed FISH probes for CA125 and the UQCRFS1 region. We studied 22 touch preparations and 14 paraffin-embedded samples of ovarian carcinomas with known CA125 serum levels, two ovarian cancer cell lines, and one ascites sample from an ovarian cancer patient. The average copy number per cell of both probes was calculated. Metaphase analyses were done on cell lines and ascites cells to localize the signals. RESULTS: The CA125 gene mapped to 19p13.2. Three of 22 (13.6%) touch preparations and 1 of 14 (7.1%) paraffin samples had amplified levels of CA125. The cell lines and ascites sample did not have amplified CA125. Unexpectedly, 3 of 22 (13.6%) touch preparations, 1 of 14 (7.1%) paraffin samples, one cell line, and the ascites sample had amplification of the UQCRFS1 region. The amplification of the UQCRFS1 region occurred in the form of homogeneously staining regions (HSRs). Only one sample had coamplification of CA125 and UQCRFS1. CONCLUSIONS: CA125 was only sometimes modestly amplified in ovarian carcinoma, even when the serum CA125 level was highly elevated. Unexpectedly, the UQCRFS1 region was also sometimes amplified as HSRs. The UQCRFS1 protein is also known as complex III of the mitochondrial respiratory chain. This product may have an important role in malignant cells.