Characterization of active mitogen-activated protein kinase in ovarian serous carcinomas
PURPOSE: Mitogen-activated protein kinase (MAPK) plays a pivotal role in signal transduction. Activation of MAPK is regulated by upstream kinases including KRAS and BRAF, which are frequently mutated in low-grade ovarian serous carcinoma. This study evaluates the expression of active MAPK in ovarian serous carcinomas, with response to treatment and survival.
EXPERIMENTAL DESIGN: Expression of active MAPK was assessed by immunohistochemistry in 207 cases of ovarian serous tumors. Immunoreactivity was correlated with tumor grade, mutational status of KRAS and BRAF, in vitro drug resistance, and clinical outcome.
RESULT: There was a lower frequency of expression of active MAPK in high-grade ovarian serous carcinomas as compared with low-grade serous tumors, including borderline tumors and low-grade serous carcinoma (P < 0.001). Active MAPK was present in all of the 19 low-grade tumors with either KRAS or BRAF mutations as well as in 14 (41%) of 34 tumors with wild-type KRAS and BRAF in both low- and high-grade carcinomas. Expression of active MAPK alone served as a good survival indicator in the 2-year follow-up (P = 0.037) but not in the 5-year follow-up (P = 0.145). However, a combination of expression of active MAPK and in vitro sensitivity of paclitaxel significantly correlated with a better prognosis in 5-year survival rate (P = 0.048) in patients with advanced-stage high-grade serous carcinoma.
CONCLUSIONS: Active MAPK is more frequently expressed in low-grade than in high-grade ovarian serous carcinoma. Active MAPK serves as a good prognostic marker in patients with high-grade serous carcinomas.
Medienart: |
Artikel |
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Erscheinungsjahr: |
2004 |
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Erschienen: |
2004 |
Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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Enthalten in: |
Clinical cancer research : an official journal of the American Association for Cancer Research - 10(2004), 19 vom: 01. Okt., Seite 6432-6 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Hsu, Chih-Yi [VerfasserIn] |
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Anmerkungen: |
Date Completed 29.03.2005 Date Revised 31.03.2022 published: Print Citation Status MEDLINE |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM151479534 |
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100 | 1 | |a Hsu, Chih-Yi |e verfasserin |4 aut | |
245 | 1 | 0 | |a Characterization of active mitogen-activated protein kinase in ovarian serous carcinomas |
264 | 1 | |c 2004 | |
336 | |a Text |b txt |2 rdacontent | ||
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500 | |a Date Completed 29.03.2005 | ||
500 | |a Date Revised 31.03.2022 | ||
500 | |a published: Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a PURPOSE: Mitogen-activated protein kinase (MAPK) plays a pivotal role in signal transduction. Activation of MAPK is regulated by upstream kinases including KRAS and BRAF, which are frequently mutated in low-grade ovarian serous carcinoma. This study evaluates the expression of active MAPK in ovarian serous carcinomas, with response to treatment and survival | ||
520 | |a EXPERIMENTAL DESIGN: Expression of active MAPK was assessed by immunohistochemistry in 207 cases of ovarian serous tumors. Immunoreactivity was correlated with tumor grade, mutational status of KRAS and BRAF, in vitro drug resistance, and clinical outcome | ||
520 | |a RESULT: There was a lower frequency of expression of active MAPK in high-grade ovarian serous carcinomas as compared with low-grade serous tumors, including borderline tumors and low-grade serous carcinoma (P < 0.001). Active MAPK was present in all of the 19 low-grade tumors with either KRAS or BRAF mutations as well as in 14 (41%) of 34 tumors with wild-type KRAS and BRAF in both low- and high-grade carcinomas. Expression of active MAPK alone served as a good survival indicator in the 2-year follow-up (P = 0.037) but not in the 5-year follow-up (P = 0.145). However, a combination of expression of active MAPK and in vitro sensitivity of paclitaxel significantly correlated with a better prognosis in 5-year survival rate (P = 0.048) in patients with advanced-stage high-grade serous carcinoma | ||
520 | |a CONCLUSIONS: Active MAPK is more frequently expressed in low-grade than in high-grade ovarian serous carcinoma. Active MAPK serves as a good prognostic marker in patients with high-grade serous carcinomas | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
650 | 7 | |a Antineoplastic Agents |2 NLM | |
650 | 7 | |a Carboplatin |2 NLM | |
650 | 7 | |a BG3F62OND5 |2 NLM | |
650 | 7 | |a Proto-Oncogene Proteins B-raf |2 NLM | |
650 | 7 | |a EC 2.7.11.1 |2 NLM | |
650 | 7 | |a Mitogen-Activated Protein Kinases |2 NLM | |
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650 | 7 | |a Oncogene Protein p21(ras) |2 NLM | |
650 | 7 | |a EC 3.6.5.2 |2 NLM | |
650 | 7 | |a Paclitaxel |2 NLM | |
650 | 7 | |a P88XT4IS4D |2 NLM | |
650 | 7 | |a Cisplatin |2 NLM | |
650 | 7 | |a Q20Q21Q62J |2 NLM | |
700 | 1 | |a Bristow, Robert |e verfasserin |4 aut | |
700 | 1 | |a Cha, Moon Seok |e verfasserin |4 aut | |
700 | 1 | |a Wang, Brant G |e verfasserin |4 aut | |
700 | 1 | |a Ho, Chung-Liang |e verfasserin |4 aut | |
700 | 1 | |a Kurman, Robert J |e verfasserin |4 aut | |
700 | 1 | |a Wang, Tian-Li |e verfasserin |4 aut | |
700 | 1 | |a Shih, Ie-Ming |e verfasserin |4 aut | |
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