Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non–small cell lung cancer
To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non–small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (A...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Machado-Rugolo, Juliana [verfasserIn] Fabro, Alexandre Todorovic [verfasserIn] Ascheri, Daniel [verfasserIn] Farhat, Cecília [verfasserIn] Ab'Saber, Alexandre Muxfeldt [verfasserIn] de Sá, Vanessa Karen [verfasserIn] Nagai, Maria Aparecida [verfasserIn] Takagaki, Teresa [verfasserIn] Terra, Ricardo [verfasserIn] Parra, Edwin Roger [verfasserIn] Capelozzi, Vera Luiza [verfasserIn] |
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| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2018 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Human pathology - New York, NY [u.a.] : Elsevier, 1970, 83, Seite 177-191 |
|---|---|
| Übergeordnetes Werk: |
volume:83 ; pages:177-191 |
| DOI / URN: |
10.1016/j.humpath.2018.08.026 |
|---|
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| 245 | 1 | 0 | |a Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non–small cell lung cancer |
| 264 | 1 | |c 2018 | |
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| 520 | |a To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non–small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma, and large cell carcinoma were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors. In patients with brain metastases, primary tumors expressed lower PIK3CA protein levels. Overexpression of p53 and a higher PD-L1 protein H-score were detected in patients who underwent surgical treatment followed by chemotherapy as compared with those who underwent only surgical treatment The absence of brain metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4, and ZEB1. The combination of protein overexpression according to IHC and mutation according to NGS was rare (ie, represented by a very low percentage of concordant cases), except for p53 and vascular endothelial growth factor. Our data suggest that protein levels detected by IHC may be a useful complementary tool when mutations are not detected by NGS and also support the idea to expand this approach beyond ADC to include squamous cell carcinoma and even large cell carcinoma, particularly for patients with unusual clinical characteristics. Conversely, well-pronounced immunogenotypic features seemed to predict the clinical outcome after univariate and multivariate analyses. Patients with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCD1LG2, or ZEB1 complemented with PD-L1 or p53 protein lower expression that only underwent surgical treatment who develop brain metastases may have the worst prognosis. | ||
| 650 | 4 | |a Epithelial-mesenchymal transition | |
| 650 | 4 | |a Immunohistochemistry | |
| 650 | 4 | |a Next-generation sequencing | |
| 650 | 4 | |a H-score | |
| 650 | 4 | |a Adenocarcinoma | |
| 650 | 4 | |a Squamouscell carcinoma | |
| 650 | 4 | |a Large cell carcinoma | |
| 700 | 1 | |a Fabro, Alexandre Todorovic |e verfasserin |4 aut | |
| 700 | 1 | |a Ascheri, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Farhat, Cecília |e verfasserin |4 aut | |
| 700 | 1 | |a Ab'Saber, Alexandre Muxfeldt |e verfasserin |4 aut | |
| 700 | 1 | |a de Sá, Vanessa Karen |e verfasserin |4 aut | |
| 700 | 1 | |a Nagai, Maria Aparecida |e verfasserin |4 aut | |
| 700 | 1 | |a Takagaki, Teresa |e verfasserin |4 aut | |
| 700 | 1 | |a Terra, Ricardo |e verfasserin |4 aut | |
| 700 | 1 | |a Parra, Edwin Roger |e verfasserin |4 aut | |
| 700 | 1 | |a Capelozzi, Vera Luiza |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Human pathology |d New York, NY [u.a.] : Elsevier, 1970 |g 83, Seite 177-191 |h Online-Ressource |w (DE-627)326644784 |w (DE-600)2041481-X |w (DE-576)094477272 |x 1532-8392 |7 nnns |
| 773 | 1 | 8 | |g volume:83 |g pages:177-191 |
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10.1016/j.humpath.2018.08.026 doi (DE-627)ELV001592416 (ELSEVIER)S0046-8177(18)30352-6 DE-627 ger DE-627 rda eng 610 DE-600 44.46 bkl 44.47 bkl Machado-Rugolo, Juliana verfasserin aut Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non–small cell lung cancer 2018 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non–small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma, and large cell carcinoma were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors. In patients with brain metastases, primary tumors expressed lower PIK3CA protein levels. Overexpression of p53 and a higher PD-L1 protein H-score were detected in patients who underwent surgical treatment followed by chemotherapy as compared with those who underwent only surgical treatment The absence of brain metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4, and ZEB1. The combination of protein overexpression according to IHC and mutation according to NGS was rare (ie, represented by a very low percentage of concordant cases), except for p53 and vascular endothelial growth factor. Our data suggest that protein levels detected by IHC may be a useful complementary tool when mutations are not detected by NGS and also support the idea to expand this approach beyond ADC to include squamous cell carcinoma and even large cell carcinoma, particularly for patients with unusual clinical characteristics. Conversely, well-pronounced immunogenotypic features seemed to predict the clinical outcome after univariate and multivariate analyses. Patients with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCD1LG2, or ZEB1 complemented with PD-L1 or p53 protein lower expression that only underwent surgical treatment who develop brain metastases may have the worst prognosis. Epithelial-mesenchymal transition Immunohistochemistry Next-generation sequencing H-score Adenocarcinoma Squamouscell carcinoma Large cell carcinoma Fabro, Alexandre Todorovic verfasserin aut Ascheri, Daniel verfasserin aut Farhat, Cecília verfasserin aut Ab'Saber, Alexandre Muxfeldt verfasserin aut de Sá, Vanessa Karen verfasserin aut Nagai, Maria Aparecida verfasserin aut Takagaki, Teresa verfasserin aut Terra, Ricardo verfasserin aut Parra, Edwin Roger verfasserin aut Capelozzi, Vera Luiza verfasserin aut Enthalten in Human pathology New York, NY [u.a.] : Elsevier, 1970 83, Seite 177-191 Online-Ressource (DE-627)326644784 (DE-600)2041481-X (DE-576)094477272 1532-8392 nnns volume:83 pages:177-191 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.46 Klinische Pathologie 44.47 Pathologie Medizin AR 83 177-191 |
| spelling |
10.1016/j.humpath.2018.08.026 doi (DE-627)ELV001592416 (ELSEVIER)S0046-8177(18)30352-6 DE-627 ger DE-627 rda eng 610 DE-600 44.46 bkl 44.47 bkl Machado-Rugolo, Juliana verfasserin aut Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non–small cell lung cancer 2018 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non–small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma, and large cell carcinoma were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors. In patients with brain metastases, primary tumors expressed lower PIK3CA protein levels. Overexpression of p53 and a higher PD-L1 protein H-score were detected in patients who underwent surgical treatment followed by chemotherapy as compared with those who underwent only surgical treatment The absence of brain metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4, and ZEB1. The combination of protein overexpression according to IHC and mutation according to NGS was rare (ie, represented by a very low percentage of concordant cases), except for p53 and vascular endothelial growth factor. Our data suggest that protein levels detected by IHC may be a useful complementary tool when mutations are not detected by NGS and also support the idea to expand this approach beyond ADC to include squamous cell carcinoma and even large cell carcinoma, particularly for patients with unusual clinical characteristics. Conversely, well-pronounced immunogenotypic features seemed to predict the clinical outcome after univariate and multivariate analyses. Patients with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCD1LG2, or ZEB1 complemented with PD-L1 or p53 protein lower expression that only underwent surgical treatment who develop brain metastases may have the worst prognosis. Epithelial-mesenchymal transition Immunohistochemistry Next-generation sequencing H-score Adenocarcinoma Squamouscell carcinoma Large cell carcinoma Fabro, Alexandre Todorovic verfasserin aut Ascheri, Daniel verfasserin aut Farhat, Cecília verfasserin aut Ab'Saber, Alexandre Muxfeldt verfasserin aut de Sá, Vanessa Karen verfasserin aut Nagai, Maria Aparecida verfasserin aut Takagaki, Teresa verfasserin aut Terra, Ricardo verfasserin aut Parra, Edwin Roger verfasserin aut Capelozzi, Vera Luiza verfasserin aut Enthalten in Human pathology New York, NY [u.a.] : Elsevier, 1970 83, Seite 177-191 Online-Ressource (DE-627)326644784 (DE-600)2041481-X (DE-576)094477272 1532-8392 nnns volume:83 pages:177-191 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.46 Klinische Pathologie 44.47 Pathologie Medizin AR 83 177-191 |
| allfields_unstemmed |
10.1016/j.humpath.2018.08.026 doi (DE-627)ELV001592416 (ELSEVIER)S0046-8177(18)30352-6 DE-627 ger DE-627 rda eng 610 DE-600 44.46 bkl 44.47 bkl Machado-Rugolo, Juliana verfasserin aut Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non–small cell lung cancer 2018 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non–small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma, and large cell carcinoma were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors. In patients with brain metastases, primary tumors expressed lower PIK3CA protein levels. Overexpression of p53 and a higher PD-L1 protein H-score were detected in patients who underwent surgical treatment followed by chemotherapy as compared with those who underwent only surgical treatment The absence of brain metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4, and ZEB1. The combination of protein overexpression according to IHC and mutation according to NGS was rare (ie, represented by a very low percentage of concordant cases), except for p53 and vascular endothelial growth factor. Our data suggest that protein levels detected by IHC may be a useful complementary tool when mutations are not detected by NGS and also support the idea to expand this approach beyond ADC to include squamous cell carcinoma and even large cell carcinoma, particularly for patients with unusual clinical characteristics. Conversely, well-pronounced immunogenotypic features seemed to predict the clinical outcome after univariate and multivariate analyses. Patients with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCD1LG2, or ZEB1 complemented with PD-L1 or p53 protein lower expression that only underwent surgical treatment who develop brain metastases may have the worst prognosis. Epithelial-mesenchymal transition Immunohistochemistry Next-generation sequencing H-score Adenocarcinoma Squamouscell carcinoma Large cell carcinoma Fabro, Alexandre Todorovic verfasserin aut Ascheri, Daniel verfasserin aut Farhat, Cecília verfasserin aut Ab'Saber, Alexandre Muxfeldt verfasserin aut de Sá, Vanessa Karen verfasserin aut Nagai, Maria Aparecida verfasserin aut Takagaki, Teresa verfasserin aut Terra, Ricardo verfasserin aut Parra, Edwin Roger verfasserin aut Capelozzi, Vera Luiza verfasserin aut Enthalten in Human pathology New York, NY [u.a.] : Elsevier, 1970 83, Seite 177-191 Online-Ressource (DE-627)326644784 (DE-600)2041481-X (DE-576)094477272 1532-8392 nnns volume:83 pages:177-191 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.46 Klinische Pathologie 44.47 Pathologie Medizin AR 83 177-191 |
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10.1016/j.humpath.2018.08.026 doi (DE-627)ELV001592416 (ELSEVIER)S0046-8177(18)30352-6 DE-627 ger DE-627 rda eng 610 DE-600 44.46 bkl 44.47 bkl Machado-Rugolo, Juliana verfasserin aut Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non–small cell lung cancer 2018 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non–small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma, and large cell carcinoma were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors. In patients with brain metastases, primary tumors expressed lower PIK3CA protein levels. Overexpression of p53 and a higher PD-L1 protein H-score were detected in patients who underwent surgical treatment followed by chemotherapy as compared with those who underwent only surgical treatment The absence of brain metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4, and ZEB1. The combination of protein overexpression according to IHC and mutation according to NGS was rare (ie, represented by a very low percentage of concordant cases), except for p53 and vascular endothelial growth factor. Our data suggest that protein levels detected by IHC may be a useful complementary tool when mutations are not detected by NGS and also support the idea to expand this approach beyond ADC to include squamous cell carcinoma and even large cell carcinoma, particularly for patients with unusual clinical characteristics. Conversely, well-pronounced immunogenotypic features seemed to predict the clinical outcome after univariate and multivariate analyses. Patients with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCD1LG2, or ZEB1 complemented with PD-L1 or p53 protein lower expression that only underwent surgical treatment who develop brain metastases may have the worst prognosis. Epithelial-mesenchymal transition Immunohistochemistry Next-generation sequencing H-score Adenocarcinoma Squamouscell carcinoma Large cell carcinoma Fabro, Alexandre Todorovic verfasserin aut Ascheri, Daniel verfasserin aut Farhat, Cecília verfasserin aut Ab'Saber, Alexandre Muxfeldt verfasserin aut de Sá, Vanessa Karen verfasserin aut Nagai, Maria Aparecida verfasserin aut Takagaki, Teresa verfasserin aut Terra, Ricardo verfasserin aut Parra, Edwin Roger verfasserin aut Capelozzi, Vera Luiza verfasserin aut Enthalten in Human pathology New York, NY [u.a.] : Elsevier, 1970 83, Seite 177-191 Online-Ressource (DE-627)326644784 (DE-600)2041481-X (DE-576)094477272 1532-8392 nnns volume:83 pages:177-191 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.46 Klinische Pathologie 44.47 Pathologie Medizin AR 83 177-191 |
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10.1016/j.humpath.2018.08.026 doi (DE-627)ELV001592416 (ELSEVIER)S0046-8177(18)30352-6 DE-627 ger DE-627 rda eng 610 DE-600 44.46 bkl 44.47 bkl Machado-Rugolo, Juliana verfasserin aut Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non–small cell lung cancer 2018 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non–small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma, and large cell carcinoma were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors. In patients with brain metastases, primary tumors expressed lower PIK3CA protein levels. Overexpression of p53 and a higher PD-L1 protein H-score were detected in patients who underwent surgical treatment followed by chemotherapy as compared with those who underwent only surgical treatment The absence of brain metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4, and ZEB1. The combination of protein overexpression according to IHC and mutation according to NGS was rare (ie, represented by a very low percentage of concordant cases), except for p53 and vascular endothelial growth factor. Our data suggest that protein levels detected by IHC may be a useful complementary tool when mutations are not detected by NGS and also support the idea to expand this approach beyond ADC to include squamous cell carcinoma and even large cell carcinoma, particularly for patients with unusual clinical characteristics. Conversely, well-pronounced immunogenotypic features seemed to predict the clinical outcome after univariate and multivariate analyses. Patients with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCD1LG2, or ZEB1 complemented with PD-L1 or p53 protein lower expression that only underwent surgical treatment who develop brain metastases may have the worst prognosis. Epithelial-mesenchymal transition Immunohistochemistry Next-generation sequencing H-score Adenocarcinoma Squamouscell carcinoma Large cell carcinoma Fabro, Alexandre Todorovic verfasserin aut Ascheri, Daniel verfasserin aut Farhat, Cecília verfasserin aut Ab'Saber, Alexandre Muxfeldt verfasserin aut de Sá, Vanessa Karen verfasserin aut Nagai, Maria Aparecida verfasserin aut Takagaki, Teresa verfasserin aut Terra, Ricardo verfasserin aut Parra, Edwin Roger verfasserin aut Capelozzi, Vera Luiza verfasserin aut Enthalten in Human pathology New York, NY [u.a.] : Elsevier, 1970 83, Seite 177-191 Online-Ressource (DE-627)326644784 (DE-600)2041481-X (DE-576)094477272 1532-8392 nnns volume:83 pages:177-191 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.46 Klinische Pathologie 44.47 Pathologie Medizin AR 83 177-191 |
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Machado-Rugolo, Juliana @@aut@@ Fabro, Alexandre Todorovic @@aut@@ Ascheri, Daniel @@aut@@ Farhat, Cecília @@aut@@ Ab'Saber, Alexandre Muxfeldt @@aut@@ de Sá, Vanessa Karen @@aut@@ Nagai, Maria Aparecida @@aut@@ Takagaki, Teresa @@aut@@ Terra, Ricardo @@aut@@ Parra, Edwin Roger @@aut@@ Capelozzi, Vera Luiza @@aut@@ |
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Machado-Rugolo, Juliana |
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Machado-Rugolo, Juliana ddc 610 bkl 44.46 bkl 44.47 misc Epithelial-mesenchymal transition misc Immunohistochemistry misc Next-generation sequencing misc H-score misc Adenocarcinoma misc Squamouscell carcinoma misc Large cell carcinoma Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non–small cell lung cancer |
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610 DE-600 44.46 bkl 44.47 bkl Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non–small cell lung cancer Epithelial-mesenchymal transition Immunohistochemistry Next-generation sequencing H-score Adenocarcinoma Squamouscell carcinoma Large cell carcinoma |
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Machado-Rugolo, Juliana Fabro, Alexandre Todorovic Ascheri, Daniel Farhat, Cecília Ab'Saber, Alexandre Muxfeldt de Sá, Vanessa Karen Nagai, Maria Aparecida Takagaki, Teresa Terra, Ricardo Parra, Edwin Roger Capelozzi, Vera Luiza |
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usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non–small cell lung cancer |
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Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non–small cell lung cancer |
| abstract |
To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non–small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma, and large cell carcinoma were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors. In patients with brain metastases, primary tumors expressed lower PIK3CA protein levels. Overexpression of p53 and a higher PD-L1 protein H-score were detected in patients who underwent surgical treatment followed by chemotherapy as compared with those who underwent only surgical treatment The absence of brain metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4, and ZEB1. The combination of protein overexpression according to IHC and mutation according to NGS was rare (ie, represented by a very low percentage of concordant cases), except for p53 and vascular endothelial growth factor. Our data suggest that protein levels detected by IHC may be a useful complementary tool when mutations are not detected by NGS and also support the idea to expand this approach beyond ADC to include squamous cell carcinoma and even large cell carcinoma, particularly for patients with unusual clinical characteristics. Conversely, well-pronounced immunogenotypic features seemed to predict the clinical outcome after univariate and multivariate analyses. Patients with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCD1LG2, or ZEB1 complemented with PD-L1 or p53 protein lower expression that only underwent surgical treatment who develop brain metastases may have the worst prognosis. |
| abstractGer |
To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non–small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma, and large cell carcinoma were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors. In patients with brain metastases, primary tumors expressed lower PIK3CA protein levels. Overexpression of p53 and a higher PD-L1 protein H-score were detected in patients who underwent surgical treatment followed by chemotherapy as compared with those who underwent only surgical treatment The absence of brain metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4, and ZEB1. The combination of protein overexpression according to IHC and mutation according to NGS was rare (ie, represented by a very low percentage of concordant cases), except for p53 and vascular endothelial growth factor. Our data suggest that protein levels detected by IHC may be a useful complementary tool when mutations are not detected by NGS and also support the idea to expand this approach beyond ADC to include squamous cell carcinoma and even large cell carcinoma, particularly for patients with unusual clinical characteristics. Conversely, well-pronounced immunogenotypic features seemed to predict the clinical outcome after univariate and multivariate analyses. Patients with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCD1LG2, or ZEB1 complemented with PD-L1 or p53 protein lower expression that only underwent surgical treatment who develop brain metastases may have the worst prognosis. |
| abstract_unstemmed |
To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non–small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma, and large cell carcinoma were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors. In patients with brain metastases, primary tumors expressed lower PIK3CA protein levels. Overexpression of p53 and a higher PD-L1 protein H-score were detected in patients who underwent surgical treatment followed by chemotherapy as compared with those who underwent only surgical treatment The absence of brain metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4, and ZEB1. The combination of protein overexpression according to IHC and mutation according to NGS was rare (ie, represented by a very low percentage of concordant cases), except for p53 and vascular endothelial growth factor. Our data suggest that protein levels detected by IHC may be a useful complementary tool when mutations are not detected by NGS and also support the idea to expand this approach beyond ADC to include squamous cell carcinoma and even large cell carcinoma, particularly for patients with unusual clinical characteristics. Conversely, well-pronounced immunogenotypic features seemed to predict the clinical outcome after univariate and multivariate analyses. Patients with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCD1LG2, or ZEB1 complemented with PD-L1 or p53 protein lower expression that only underwent surgical treatment who develop brain metastases may have the worst prognosis. |
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Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non–small cell lung cancer |
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