Dataset Information

The effect of chemotherapy on expression of folate receptor-alpha in ovarian cancer.

ABSTRACT:

Background

Folate receptor alpha (FR-?) has been identified as a potential target in ovarian cancer for diagnostic and therapeutic purposes, based on its overexpression in serous epithelial ovarian carcinoma. The effect of chemotherapy on FR-? expression may be important in the applicability of FR-? directed agents in the case of residual tumor tissue. The objective of this study was to assess FR-? expression in ovarian carcinoma and to evaluate whether FR-? expression is altered by chemotherapy.

Materials & methods

FR-? expression was analyzed by semi-quantitative scoring of immunohistochemical staining on tissue microarrays (TMAs) from a database containing 361 ovarian cancer tissue samples, of which 210 serous and 116 non-serous carcinoma (35 missing). Serous carcinoma samples included 28 matched samples with tissue from both primary surgery and interval debulking surgery, and 12 matched samples with tissue from both primary surgery and surgery for recurrent disease.

Results

FR-? expression was seen in 81.8% of serous ovarian cancers versus 39.9% of non-serous carcinomas (p?ConclusionFR-? was expressed in the majority of serous ovarian tumors, although >50% of cases showed only weak expression. Chemotherapy did not alter expression rates in remaining vital tumor tissue, indicating that folate-targeted agents may have a place in the treatment for ovarian cancer, before as well as after chemotherapy. Furthermore, FR-? status did not influence survival.

SUBMITTER: Crane LM

PROVIDER: S-EPMC3268989 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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The effect of chemotherapy on expression of folate receptor-alpha in ovarian cancer.

Crane Lucia M A LM Arts Henriette J G HJ van Oosten Marleen M Low Philip S PS van der Zee Ate G J AG van Dam Gooitzen M GM Bart Joost J

Cellular oncology (Dordrecht, Netherlands) 20110607 1

<h4>Background</h4>Folate receptor alpha (FR-α) has been identified as a potential target in ovarian cancer for diagnostic and therapeutic purposes, based on its overexpression in serous epithelial ovarian carcinoma. The effect of chemotherapy on FR-α expression may be important in the applicability of FR-α directed agents in the case of residual tumor tissue. The objective of this study was to assess FR-α expression in ovarian carcinoma and to evaluate whether FR-α expression is altered by chem ...[more]

PMID: 21647742

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Project description:Complete resection of tumor lesions in advanced stage ovarian cancer patients is of utmost importance, since the extent of residual disease after surgery strongly affects survival. Intraoperative imaging may be useful to improve surgery in these patients. Farletuzumab is a humanized IgG1 antibody that specifically recognizes the folate receptor alpha (FRα). Labeled with a radiolabel and a fluorescent dye, farletuzumab may be used for the intraoperative detection of ovarian cancer lesions. The current aim is to demonstrate the feasibility of FRα-targeted dual-modality imaging using 111In-farletuzumab-IRDye800CW in an intraperitoneal ovarian cancer model. Biodistribution studies were performed 3 days after injection of 3, 10, 30, or 100 μg of 111In-farletuzumab-IRDye800CW in mice with subcutaneous IGROV-1 tumors (5 mice per group). In mice with intraperitoneal IGROV-1 tumors the nonspecific uptake of 111In-farletuzumab-IRDye800CW was determined by coinjecting an excess of unlabeled farletuzumab. MicroSPECT/CT and fluorescence imaging were performed 3 days after injection of 10 μg of 111In-farletuzumab-IRDye800CW. FRα expression in tumors was determined immunohistochemically. Optimal tumor-to-blood-ratios (3.4-3.7) were obtained at protein doses up to 30 μg. Multiple intra-abdominal tumor lesions were clearly visualized by microSPECT/CT, while uptake in normal tissues was limited. Fluorescence imaging was used to visualize and guide resection of superficial tumors. Coinjection of an excess of unlabeled farletuzumab significantly decreased tumor uptake of 111In-farletuzumab-IRDye800CW (69.4 ± 27.6 versus 18.3 ± 2.2% ID/g, p < 0.05). Immunohistochemical analyses demonstrated that the radioactive and fluorescent signal corresponded with FRα-expressing tumor lesions. FRα-targeted SPECT/fluorescence imaging using 111In-farletuzumab-IRDye800CW can be used to detect ovarian cancer in vivo and could be a valuable tool for enhanced intraoperative tumor visualization in patients with intraperitoneal metastases of ovarian cancer.

Dataset Information

The effect of chemotherapy on expression of folate receptor-alpha in ovarian cancer.

Background

Materials & methods

Results

Publications

The effect of chemotherapy on expression of folate receptor-alpha in ovarian cancer.

Similar Datasets

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