Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma
Abstract Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potenti...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Schmoeckel, Elisa [verfasserIn] Hofmann, Sophie [verfasserIn] Fromberger, Daniel [verfasserIn] Rottmann, Miriam [verfasserIn] Luthardt, Beate [verfasserIn] Burges, Alexander [verfasserIn] Jeschke, Udo [verfasserIn] Kirchner, Thomas [verfasserIn] Lax, Sigurd F. [verfasserIn] Mayr, Doris [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2019 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Virchows Archiv - Berlin : Springer, 1847, 474(2019), 5 vom: 07. Feb., Seite 599-608 |
|---|---|
| Übergeordnetes Werk: |
volume:474 ; year:2019 ; number:5 ; day:07 ; month:02 ; pages:599-608 |
| Links: |
|---|
| DOI / URN: |
10.1007/s00428-019-02528-6 |
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| Katalog-ID: |
SPR005825822 |
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| 245 | 1 | 0 | |a Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma |
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| 520 | |a Abstract Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients’ survival. ALK/EML4 fusion was found in two cases (0.74%): one high-grade serous and one endometrioid carcinoma. MMR deficiency was only present in one case of stage IV high-grade serous carcinoma. Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy. PD-L1 is also of prognostic impact. ALK/EML4 fusion is very rare in OC and not a putative therapeutic target. | ||
| 650 | 4 | |a Ovarian carcinoma |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a HER2 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a ALK/EML4 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a PD-L1 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Mismatch repair deficiency |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Microsatellite instability |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Hofmann, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Fromberger, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Rottmann, Miriam |e verfasserin |4 aut | |
| 700 | 1 | |a Luthardt, Beate |e verfasserin |4 aut | |
| 700 | 1 | |a Burges, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Jeschke, Udo |e verfasserin |4 aut | |
| 700 | 1 | |a Kirchner, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Lax, Sigurd F. |e verfasserin |4 aut | |
| 700 | 1 | |a Mayr, Doris |e verfasserin |4 aut | |
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10.1007/s00428-019-02528-6 doi (DE-627)SPR005825822 (SPR)s00428-019-02528-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.47 bkl Schmoeckel, Elisa verfasserin aut Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients’ survival. ALK/EML4 fusion was found in two cases (0.74%): one high-grade serous and one endometrioid carcinoma. MMR deficiency was only present in one case of stage IV high-grade serous carcinoma. Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy. PD-L1 is also of prognostic impact. ALK/EML4 fusion is very rare in OC and not a putative therapeutic target. Ovarian carcinoma (dpeaa)DE-He213 HER2 (dpeaa)DE-He213 ALK/EML4 (dpeaa)DE-He213 PD-L1 (dpeaa)DE-He213 Mismatch repair deficiency (dpeaa)DE-He213 Microsatellite instability (dpeaa)DE-He213 Hofmann, Sophie verfasserin aut Fromberger, Daniel verfasserin aut Rottmann, Miriam verfasserin aut Luthardt, Beate verfasserin aut Burges, Alexander verfasserin aut Jeschke, Udo verfasserin aut Kirchner, Thomas verfasserin aut Lax, Sigurd F. verfasserin aut Mayr, Doris verfasserin aut Enthalten in Virchows Archiv Berlin : Springer, 1847 474(2019), 5 vom: 07. Feb., Seite 599-608 (DE-627)254910645 (DE-600)1463276-7 1432-2307 nnns volume:474 year:2019 number:5 day:07 month:02 pages:599-608 https://dx.doi.org/10.1007/s00428-019-02528-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.47 ASE AR 474 2019 5 07 02 599-608 |
| spelling |
10.1007/s00428-019-02528-6 doi (DE-627)SPR005825822 (SPR)s00428-019-02528-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.47 bkl Schmoeckel, Elisa verfasserin aut Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients’ survival. ALK/EML4 fusion was found in two cases (0.74%): one high-grade serous and one endometrioid carcinoma. MMR deficiency was only present in one case of stage IV high-grade serous carcinoma. Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy. PD-L1 is also of prognostic impact. ALK/EML4 fusion is very rare in OC and not a putative therapeutic target. Ovarian carcinoma (dpeaa)DE-He213 HER2 (dpeaa)DE-He213 ALK/EML4 (dpeaa)DE-He213 PD-L1 (dpeaa)DE-He213 Mismatch repair deficiency (dpeaa)DE-He213 Microsatellite instability (dpeaa)DE-He213 Hofmann, Sophie verfasserin aut Fromberger, Daniel verfasserin aut Rottmann, Miriam verfasserin aut Luthardt, Beate verfasserin aut Burges, Alexander verfasserin aut Jeschke, Udo verfasserin aut Kirchner, Thomas verfasserin aut Lax, Sigurd F. verfasserin aut Mayr, Doris verfasserin aut Enthalten in Virchows Archiv Berlin : Springer, 1847 474(2019), 5 vom: 07. Feb., Seite 599-608 (DE-627)254910645 (DE-600)1463276-7 1432-2307 nnns volume:474 year:2019 number:5 day:07 month:02 pages:599-608 https://dx.doi.org/10.1007/s00428-019-02528-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.47 ASE AR 474 2019 5 07 02 599-608 |
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10.1007/s00428-019-02528-6 doi (DE-627)SPR005825822 (SPR)s00428-019-02528-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.47 bkl Schmoeckel, Elisa verfasserin aut Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients’ survival. ALK/EML4 fusion was found in two cases (0.74%): one high-grade serous and one endometrioid carcinoma. MMR deficiency was only present in one case of stage IV high-grade serous carcinoma. Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy. PD-L1 is also of prognostic impact. ALK/EML4 fusion is very rare in OC and not a putative therapeutic target. Ovarian carcinoma (dpeaa)DE-He213 HER2 (dpeaa)DE-He213 ALK/EML4 (dpeaa)DE-He213 PD-L1 (dpeaa)DE-He213 Mismatch repair deficiency (dpeaa)DE-He213 Microsatellite instability (dpeaa)DE-He213 Hofmann, Sophie verfasserin aut Fromberger, Daniel verfasserin aut Rottmann, Miriam verfasserin aut Luthardt, Beate verfasserin aut Burges, Alexander verfasserin aut Jeschke, Udo verfasserin aut Kirchner, Thomas verfasserin aut Lax, Sigurd F. verfasserin aut Mayr, Doris verfasserin aut Enthalten in Virchows Archiv Berlin : Springer, 1847 474(2019), 5 vom: 07. Feb., Seite 599-608 (DE-627)254910645 (DE-600)1463276-7 1432-2307 nnns volume:474 year:2019 number:5 day:07 month:02 pages:599-608 https://dx.doi.org/10.1007/s00428-019-02528-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.47 ASE AR 474 2019 5 07 02 599-608 |
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10.1007/s00428-019-02528-6 doi (DE-627)SPR005825822 (SPR)s00428-019-02528-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.47 bkl Schmoeckel, Elisa verfasserin aut Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients’ survival. ALK/EML4 fusion was found in two cases (0.74%): one high-grade serous and one endometrioid carcinoma. MMR deficiency was only present in one case of stage IV high-grade serous carcinoma. Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy. PD-L1 is also of prognostic impact. ALK/EML4 fusion is very rare in OC and not a putative therapeutic target. Ovarian carcinoma (dpeaa)DE-He213 HER2 (dpeaa)DE-He213 ALK/EML4 (dpeaa)DE-He213 PD-L1 (dpeaa)DE-He213 Mismatch repair deficiency (dpeaa)DE-He213 Microsatellite instability (dpeaa)DE-He213 Hofmann, Sophie verfasserin aut Fromberger, Daniel verfasserin aut Rottmann, Miriam verfasserin aut Luthardt, Beate verfasserin aut Burges, Alexander verfasserin aut Jeschke, Udo verfasserin aut Kirchner, Thomas verfasserin aut Lax, Sigurd F. verfasserin aut Mayr, Doris verfasserin aut Enthalten in Virchows Archiv Berlin : Springer, 1847 474(2019), 5 vom: 07. Feb., Seite 599-608 (DE-627)254910645 (DE-600)1463276-7 1432-2307 nnns volume:474 year:2019 number:5 day:07 month:02 pages:599-608 https://dx.doi.org/10.1007/s00428-019-02528-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.47 ASE AR 474 2019 5 07 02 599-608 |
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10.1007/s00428-019-02528-6 doi (DE-627)SPR005825822 (SPR)s00428-019-02528-6-e DE-627 ger DE-627 rakwb eng 610 ASE 44.47 bkl Schmoeckel, Elisa verfasserin aut Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients’ survival. ALK/EML4 fusion was found in two cases (0.74%): one high-grade serous and one endometrioid carcinoma. MMR deficiency was only present in one case of stage IV high-grade serous carcinoma. Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy. PD-L1 is also of prognostic impact. ALK/EML4 fusion is very rare in OC and not a putative therapeutic target. Ovarian carcinoma (dpeaa)DE-He213 HER2 (dpeaa)DE-He213 ALK/EML4 (dpeaa)DE-He213 PD-L1 (dpeaa)DE-He213 Mismatch repair deficiency (dpeaa)DE-He213 Microsatellite instability (dpeaa)DE-He213 Hofmann, Sophie verfasserin aut Fromberger, Daniel verfasserin aut Rottmann, Miriam verfasserin aut Luthardt, Beate verfasserin aut Burges, Alexander verfasserin aut Jeschke, Udo verfasserin aut Kirchner, Thomas verfasserin aut Lax, Sigurd F. verfasserin aut Mayr, Doris verfasserin aut Enthalten in Virchows Archiv Berlin : Springer, 1847 474(2019), 5 vom: 07. Feb., Seite 599-608 (DE-627)254910645 (DE-600)1463276-7 1432-2307 nnns volume:474 year:2019 number:5 day:07 month:02 pages:599-608 https://dx.doi.org/10.1007/s00428-019-02528-6 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.47 ASE AR 474 2019 5 07 02 599-608 |
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Enthalten in Virchows Archiv 474(2019), 5 vom: 07. Feb., Seite 599-608 volume:474 year:2019 number:5 day:07 month:02 pages:599-608 |
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Enthalten in Virchows Archiv 474(2019), 5 vom: 07. Feb., Seite 599-608 volume:474 year:2019 number:5 day:07 month:02 pages:599-608 |
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Ovarian carcinoma HER2 ALK/EML4 PD-L1 Mismatch repair deficiency Microsatellite instability |
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Schmoeckel, Elisa @@aut@@ Hofmann, Sophie @@aut@@ Fromberger, Daniel @@aut@@ Rottmann, Miriam @@aut@@ Luthardt, Beate @@aut@@ Burges, Alexander @@aut@@ Jeschke, Udo @@aut@@ Kirchner, Thomas @@aut@@ Lax, Sigurd F. @@aut@@ Mayr, Doris @@aut@@ |
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Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients’ survival. ALK/EML4 fusion was found in two cases (0.74%): one high-grade serous and one endometrioid carcinoma. MMR deficiency was only present in one case of stage IV high-grade serous carcinoma. Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy. PD-L1 is also of prognostic impact. 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|
| author |
Schmoeckel, Elisa |
| spellingShingle |
Schmoeckel, Elisa ddc 610 bkl 44.47 misc Ovarian carcinoma misc HER2 misc ALK/EML4 misc PD-L1 misc Mismatch repair deficiency misc Microsatellite instability Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma |
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1432-2307 |
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610 ASE 44.47 bkl Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma Ovarian carcinoma (dpeaa)DE-He213 HER2 (dpeaa)DE-He213 ALK/EML4 (dpeaa)DE-He213 PD-L1 (dpeaa)DE-He213 Mismatch repair deficiency (dpeaa)DE-He213 Microsatellite instability (dpeaa)DE-He213 |
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ddc 610 bkl 44.47 misc Ovarian carcinoma misc HER2 misc ALK/EML4 misc PD-L1 misc Mismatch repair deficiency misc Microsatellite instability |
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ddc 610 bkl 44.47 misc Ovarian carcinoma misc HER2 misc ALK/EML4 misc PD-L1 misc Mismatch repair deficiency misc Microsatellite instability |
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ddc 610 bkl 44.47 misc Ovarian carcinoma misc HER2 misc ALK/EML4 misc PD-L1 misc Mismatch repair deficiency misc Microsatellite instability |
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Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma |
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Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma |
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Schmoeckel, Elisa |
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Virchows Archiv |
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Schmoeckel, Elisa Hofmann, Sophie Fromberger, Daniel Rottmann, Miriam Luthardt, Beate Burges, Alexander Jeschke, Udo Kirchner, Thomas Lax, Sigurd F. Mayr, Doris |
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Schmoeckel, Elisa |
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10.1007/s00428-019-02528-6 |
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610 |
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verfasserin |
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comprehensive analysis of pd-l1 expression, her2 amplification, alk/eml4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma |
| title_auth |
Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma |
| abstract |
Abstract Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients’ survival. ALK/EML4 fusion was found in two cases (0.74%): one high-grade serous and one endometrioid carcinoma. MMR deficiency was only present in one case of stage IV high-grade serous carcinoma. Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy. PD-L1 is also of prognostic impact. ALK/EML4 fusion is very rare in OC and not a putative therapeutic target. |
| abstractGer |
Abstract Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients’ survival. ALK/EML4 fusion was found in two cases (0.74%): one high-grade serous and one endometrioid carcinoma. MMR deficiency was only present in one case of stage IV high-grade serous carcinoma. Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy. PD-L1 is also of prognostic impact. ALK/EML4 fusion is very rare in OC and not a putative therapeutic target. |
| abstract_unstemmed |
Abstract Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients’ survival. ALK/EML4 fusion was found in two cases (0.74%): one high-grade serous and one endometrioid carcinoma. MMR deficiency was only present in one case of stage IV high-grade serous carcinoma. Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy. PD-L1 is also of prognostic impact. ALK/EML4 fusion is very rare in OC and not a putative therapeutic target. |
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Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma |
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Hofmann, Sophie Fromberger, Daniel Rottmann, Miriam Luthardt, Beate Burges, Alexander Jeschke, Udo Kirchner, Thomas Lax, Sigurd F. Mayr, Doris |
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| score |
7.4000826 |