Screening of BRCA1 Mutation Using Immunohistochemical Staining with C-Terminal and N-Terminal Antibodies in Familial Ovarian Cancers |
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| Authors: | Katsunori Kashima Takashi Oite Yoichi Aoki Koichi Takakuwa Hiroshi Aida Hiroshi Nagata Masayuki Sekine Hong Jun Wu Yasuo Hirai Yuichi Wada Kaichiro Yamamoto Kazuo Hasegawa Takahiko Sonoda Takeshi Maruo Ichiro Nagata Masayuki Ohno Mitsuaki Suzuki Iwao Kobayashi Kazuo Kuzuya Takeshi Takahashi Yuichi Torii Kenichi Tanaka |
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| Institution: | Department of Obstetrics and Gynecology, Niigata University School of Medicine, 1–757 Asahimachi-dori, Niigata 951–8510;Department of Cellular Physiology Institute of Nephrology, Niigata University School of Medicine, 1–757 Asahimachi-dori, Niigata 951–8510;Department of Gynecology, Cancer Institute Hospital, Tokyo 170–0012;Sendai National Hospital, Miyagi 983–8520;Department of Obstetrics and Gynecology, Kinki University School of Medicine, Osaka 589–8511;Hyogo Medical Center for Adults, Hyogo 673–0021;Department of Gynecology, National Cancer Center, Tokyo 104–0045;Department of Obstetrics and Gynecology, Kobe University School of Medicine, Hyogo 650–0017;Department of Obstetrics and Gynecology, National Defense Medical College, Saitama 359–8513;Department of Obstetrics and Gynecology, Kagawa Medical University, Kagawa 761–0793;Department of Obstetrics and Gynecology, Jichi Medical School, Tochigi 329–0498;Nagoya Daini Red Cross Hospital, Aichi 466–8650;Aichi Cancer Center, Aichi 464–8681;Niigata Cancer Center, Niigata 951–8133;Seirei-Hamamatsu Hospital, Shizuoka 430–0906 |
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| Abstract: | We examined the subcellular localization of BRCA1 proteins using immunohistochemical staining with C-terminal (GLK-2 antibody) and N-terminal (Ab-2 antibody) monoclonal antibodies in 44 familial ovarian cancers. Among these, 24 cases were associated with 13 independent germ-line mutations of BRCA1 , and loss of heterozygosity (LOH) at one or more BRCA1 microsatellite markers was found in all 21 informative tumors tested. With GLK-2 antibody, cytoplasmic staining was observed in 15 of 16 tumors (93.8%) with mutation in exon 11, and BRCA1 staining was absent in 8 of 8 tumors (100%) with mutation in exons other than exon 11. When immunohistochemical staining was performed with Ab-2 antibody, both nuclear and cytoplasmic staining were observed in 14 of 16 tumors (87.5%) with mutation in exon 11. Interestingly, nuclear staining was observed in 3 of 3 tumors (100%) with mutation downstream of exon 11, even though no staining was detected in 5 of 5 tumors (100%) with mutation upstream of exon 11. On the other hand, in familial ovarian cancers without BRCA1 mutations, nuclear staining or both nuclear and cytoplasmic staining was observed in 18 of 20 specimens (90%) and 20 of 20 specimens (100%) with GLK-2 antibody and with Ab-2 antibody, respectively. These results suggest that an immunohistochemical assay in combination with employing the C-terminal and the N-terminal antibodies appears to have potential as a reliable and useful technique for the screening of BRCA1 mutations, at least to predict the status of mutation, upstream or downstream of exon 11. |
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| Keywords: | Familial ovarian cancer BRCA1 Subcellular localization Splice variant Immunohistochemistry |
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