TGFβ1 pathway components in breast cancer tissue from aggressive subtypes correlate with better prognostic parameters in ER-positive and p53-negative cancers
Abstract Background TGFβ signaling exerts context-specific effects in breast cancer (BC) pathogenesis and single nucleotide polymorphisms (SNPs) in TGFβ-signaling components play a role in the genetic control of their expression and in BC susceptibility and clinical presentation. However, studies in...
Ausführliche Beschreibung
Autor*in: |
Glauco Akelinghton Freire Vitiello [verfasserIn] Marla Karine Amarante [verfasserIn] Jefferson Crespigio [verfasserIn] Bruna Karina Banin Hirata [verfasserIn] Nathalia de Sousa Pereira [verfasserIn] Karen Brajão de Oliveira [verfasserIn] Roberta Losi Guembarovski [verfasserIn] Maria Angelica Ehara Watanabe [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2021 |
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In: Surgical and Experimental Pathology - BMC, 2019, 4(2021), 1, Seite 13 |
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volume:4 ; year:2021 ; number:1 ; pages:13 |
Links: |
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DOI / URN: |
10.1186/s42047-021-00097-0 |
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Katalog-ID: |
DOAJ057936544 |
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520 | |a Abstract Background TGFβ signaling exerts context-specific effects in breast cancer (BC) pathogenesis and single nucleotide polymorphisms (SNPs) in TGFβ-signaling components play a role in the genetic control of their expression and in BC susceptibility and clinical presentation. However, studies investigating the association between the TGFβ-signaling molecules and BC prognosis rarely considered disease subtypes and SNPs. Therefore, the present study aimed to evaluate the expression of TGFβ-signaling components in BC tissue from patients with available data regarding TGFB1 and TGFBR2 SNPs and plasmatic TGFβ1 levels. Methods Immunostaining for TGFβ1, TGFβRII and phosphorylated (p)-SMAD2/3 was investigated in primary tumor tissue from 34 patients with luminal-B-HER2+ (LB-HER2), HER2-enriched (HER2) and triple negative (TN) BC subtypes genotyped for TGFB1 (rs1800468, rs1800469, rs1800470 and rs1800471) and TGFBR2 (rs3087465) SNPs. Results Strong positive correlations were observed between TGFβ1, TGFβRII and p-SMAD2/3 in tumor tissue, and an inverse correlation was observed between intratumor and plasmatic TGFβ1 levels in TN BCs. In LB-HER2+ tumors, p-SMAD2/3 was associated with older age at diagnosis and inversely correlated with p53 staining and lymph-node metastasis, while tumor-size negatively correlated with TGFβ1 and TGFβRII in this BC subgroup. Also, in p53-negative BCs, tumor size and Ki67 negatively correlated with both TGFβ1, TGFβRII and p-SMAD2/3. No correlation was found between SNPs and TGFβ1-signaling components expression. Conclusion TGFβ1 canonical signaling is activated in approximately half of BCs, and correlation between TGFβ components indicate a paracrine activation, which may exert tumor suppressor effects in p53-negative or Luminal-B-HER2+ subgroups. | ||
650 | 4 | |a Transforming growth factor beta | |
650 | 4 | |a Breast neoplasm | |
650 | 4 | |a Immunohistochemistry | |
650 | 4 | |a Biomarkers | |
650 | 4 | |a Prognosis | |
650 | 4 | |a Polymorphisms | |
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700 | 0 | |a Maria Angelica Ehara Watanabe |e verfasserin |4 aut | |
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10.1186/s42047-021-00097-0 doi (DE-627)DOAJ057936544 (DE-599)DOAJ8bad43f3d1824ec2b108ab4a5c597844 DE-627 ger DE-627 rakwb eng RD1-811 RB1-214 Glauco Akelinghton Freire Vitiello verfasserin aut TGFβ1 pathway components in breast cancer tissue from aggressive subtypes correlate with better prognostic parameters in ER-positive and p53-negative cancers 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background TGFβ signaling exerts context-specific effects in breast cancer (BC) pathogenesis and single nucleotide polymorphisms (SNPs) in TGFβ-signaling components play a role in the genetic control of their expression and in BC susceptibility and clinical presentation. However, studies investigating the association between the TGFβ-signaling molecules and BC prognosis rarely considered disease subtypes and SNPs. Therefore, the present study aimed to evaluate the expression of TGFβ-signaling components in BC tissue from patients with available data regarding TGFB1 and TGFBR2 SNPs and plasmatic TGFβ1 levels. Methods Immunostaining for TGFβ1, TGFβRII and phosphorylated (p)-SMAD2/3 was investigated in primary tumor tissue from 34 patients with luminal-B-HER2+ (LB-HER2), HER2-enriched (HER2) and triple negative (TN) BC subtypes genotyped for TGFB1 (rs1800468, rs1800469, rs1800470 and rs1800471) and TGFBR2 (rs3087465) SNPs. Results Strong positive correlations were observed between TGFβ1, TGFβRII and p-SMAD2/3 in tumor tissue, and an inverse correlation was observed between intratumor and plasmatic TGFβ1 levels in TN BCs. In LB-HER2+ tumors, p-SMAD2/3 was associated with older age at diagnosis and inversely correlated with p53 staining and lymph-node metastasis, while tumor-size negatively correlated with TGFβ1 and TGFβRII in this BC subgroup. Also, in p53-negative BCs, tumor size and Ki67 negatively correlated with both TGFβ1, TGFβRII and p-SMAD2/3. No correlation was found between SNPs and TGFβ1-signaling components expression. Conclusion TGFβ1 canonical signaling is activated in approximately half of BCs, and correlation between TGFβ components indicate a paracrine activation, which may exert tumor suppressor effects in p53-negative or Luminal-B-HER2+ subgroups. Transforming growth factor beta Breast neoplasm Immunohistochemistry Biomarkers Prognosis Polymorphisms Surgery Pathology Marla Karine Amarante verfasserin aut Jefferson Crespigio verfasserin aut Bruna Karina Banin Hirata verfasserin aut Nathalia de Sousa Pereira verfasserin aut Karen Brajão de Oliveira verfasserin aut Roberta Losi Guembarovski verfasserin aut Maria Angelica Ehara Watanabe verfasserin aut In Surgical and Experimental Pathology BMC, 2019 4(2021), 1, Seite 13 (DE-627)1040711715 25208454 nnns volume:4 year:2021 number:1 pages:13 https://doi.org/10.1186/s42047-021-00097-0 kostenfrei https://doaj.org/article/8bad43f3d1824ec2b108ab4a5c597844 kostenfrei https://doi.org/10.1186/s42047-021-00097-0 kostenfrei https://doaj.org/toc/2520-8454 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2021 1 13 |
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10.1186/s42047-021-00097-0 doi (DE-627)DOAJ057936544 (DE-599)DOAJ8bad43f3d1824ec2b108ab4a5c597844 DE-627 ger DE-627 rakwb eng RD1-811 RB1-214 Glauco Akelinghton Freire Vitiello verfasserin aut TGFβ1 pathway components in breast cancer tissue from aggressive subtypes correlate with better prognostic parameters in ER-positive and p53-negative cancers 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background TGFβ signaling exerts context-specific effects in breast cancer (BC) pathogenesis and single nucleotide polymorphisms (SNPs) in TGFβ-signaling components play a role in the genetic control of their expression and in BC susceptibility and clinical presentation. However, studies investigating the association between the TGFβ-signaling molecules and BC prognosis rarely considered disease subtypes and SNPs. Therefore, the present study aimed to evaluate the expression of TGFβ-signaling components in BC tissue from patients with available data regarding TGFB1 and TGFBR2 SNPs and plasmatic TGFβ1 levels. Methods Immunostaining for TGFβ1, TGFβRII and phosphorylated (p)-SMAD2/3 was investigated in primary tumor tissue from 34 patients with luminal-B-HER2+ (LB-HER2), HER2-enriched (HER2) and triple negative (TN) BC subtypes genotyped for TGFB1 (rs1800468, rs1800469, rs1800470 and rs1800471) and TGFBR2 (rs3087465) SNPs. Results Strong positive correlations were observed between TGFβ1, TGFβRII and p-SMAD2/3 in tumor tissue, and an inverse correlation was observed between intratumor and plasmatic TGFβ1 levels in TN BCs. In LB-HER2+ tumors, p-SMAD2/3 was associated with older age at diagnosis and inversely correlated with p53 staining and lymph-node metastasis, while tumor-size negatively correlated with TGFβ1 and TGFβRII in this BC subgroup. Also, in p53-negative BCs, tumor size and Ki67 negatively correlated with both TGFβ1, TGFβRII and p-SMAD2/3. No correlation was found between SNPs and TGFβ1-signaling components expression. Conclusion TGFβ1 canonical signaling is activated in approximately half of BCs, and correlation between TGFβ components indicate a paracrine activation, which may exert tumor suppressor effects in p53-negative or Luminal-B-HER2+ subgroups. Transforming growth factor beta Breast neoplasm Immunohistochemistry Biomarkers Prognosis Polymorphisms Surgery Pathology Marla Karine Amarante verfasserin aut Jefferson Crespigio verfasserin aut Bruna Karina Banin Hirata verfasserin aut Nathalia de Sousa Pereira verfasserin aut Karen Brajão de Oliveira verfasserin aut Roberta Losi Guembarovski verfasserin aut Maria Angelica Ehara Watanabe verfasserin aut In Surgical and Experimental Pathology BMC, 2019 4(2021), 1, Seite 13 (DE-627)1040711715 25208454 nnns volume:4 year:2021 number:1 pages:13 https://doi.org/10.1186/s42047-021-00097-0 kostenfrei https://doaj.org/article/8bad43f3d1824ec2b108ab4a5c597844 kostenfrei https://doi.org/10.1186/s42047-021-00097-0 kostenfrei https://doaj.org/toc/2520-8454 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2021 1 13 |
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10.1186/s42047-021-00097-0 doi (DE-627)DOAJ057936544 (DE-599)DOAJ8bad43f3d1824ec2b108ab4a5c597844 DE-627 ger DE-627 rakwb eng RD1-811 RB1-214 Glauco Akelinghton Freire Vitiello verfasserin aut TGFβ1 pathway components in breast cancer tissue from aggressive subtypes correlate with better prognostic parameters in ER-positive and p53-negative cancers 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background TGFβ signaling exerts context-specific effects in breast cancer (BC) pathogenesis and single nucleotide polymorphisms (SNPs) in TGFβ-signaling components play a role in the genetic control of their expression and in BC susceptibility and clinical presentation. However, studies investigating the association between the TGFβ-signaling molecules and BC prognosis rarely considered disease subtypes and SNPs. Therefore, the present study aimed to evaluate the expression of TGFβ-signaling components in BC tissue from patients with available data regarding TGFB1 and TGFBR2 SNPs and plasmatic TGFβ1 levels. Methods Immunostaining for TGFβ1, TGFβRII and phosphorylated (p)-SMAD2/3 was investigated in primary tumor tissue from 34 patients with luminal-B-HER2+ (LB-HER2), HER2-enriched (HER2) and triple negative (TN) BC subtypes genotyped for TGFB1 (rs1800468, rs1800469, rs1800470 and rs1800471) and TGFBR2 (rs3087465) SNPs. Results Strong positive correlations were observed between TGFβ1, TGFβRII and p-SMAD2/3 in tumor tissue, and an inverse correlation was observed between intratumor and plasmatic TGFβ1 levels in TN BCs. In LB-HER2+ tumors, p-SMAD2/3 was associated with older age at diagnosis and inversely correlated with p53 staining and lymph-node metastasis, while tumor-size negatively correlated with TGFβ1 and TGFβRII in this BC subgroup. Also, in p53-negative BCs, tumor size and Ki67 negatively correlated with both TGFβ1, TGFβRII and p-SMAD2/3. No correlation was found between SNPs and TGFβ1-signaling components expression. Conclusion TGFβ1 canonical signaling is activated in approximately half of BCs, and correlation between TGFβ components indicate a paracrine activation, which may exert tumor suppressor effects in p53-negative or Luminal-B-HER2+ subgroups. Transforming growth factor beta Breast neoplasm Immunohistochemistry Biomarkers Prognosis Polymorphisms Surgery Pathology Marla Karine Amarante verfasserin aut Jefferson Crespigio verfasserin aut Bruna Karina Banin Hirata verfasserin aut Nathalia de Sousa Pereira verfasserin aut Karen Brajão de Oliveira verfasserin aut Roberta Losi Guembarovski verfasserin aut Maria Angelica Ehara Watanabe verfasserin aut In Surgical and Experimental Pathology BMC, 2019 4(2021), 1, Seite 13 (DE-627)1040711715 25208454 nnns volume:4 year:2021 number:1 pages:13 https://doi.org/10.1186/s42047-021-00097-0 kostenfrei https://doaj.org/article/8bad43f3d1824ec2b108ab4a5c597844 kostenfrei https://doi.org/10.1186/s42047-021-00097-0 kostenfrei https://doaj.org/toc/2520-8454 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2021 1 13 |
allfieldsGer |
10.1186/s42047-021-00097-0 doi (DE-627)DOAJ057936544 (DE-599)DOAJ8bad43f3d1824ec2b108ab4a5c597844 DE-627 ger DE-627 rakwb eng RD1-811 RB1-214 Glauco Akelinghton Freire Vitiello verfasserin aut TGFβ1 pathway components in breast cancer tissue from aggressive subtypes correlate with better prognostic parameters in ER-positive and p53-negative cancers 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background TGFβ signaling exerts context-specific effects in breast cancer (BC) pathogenesis and single nucleotide polymorphisms (SNPs) in TGFβ-signaling components play a role in the genetic control of their expression and in BC susceptibility and clinical presentation. However, studies investigating the association between the TGFβ-signaling molecules and BC prognosis rarely considered disease subtypes and SNPs. Therefore, the present study aimed to evaluate the expression of TGFβ-signaling components in BC tissue from patients with available data regarding TGFB1 and TGFBR2 SNPs and plasmatic TGFβ1 levels. Methods Immunostaining for TGFβ1, TGFβRII and phosphorylated (p)-SMAD2/3 was investigated in primary tumor tissue from 34 patients with luminal-B-HER2+ (LB-HER2), HER2-enriched (HER2) and triple negative (TN) BC subtypes genotyped for TGFB1 (rs1800468, rs1800469, rs1800470 and rs1800471) and TGFBR2 (rs3087465) SNPs. Results Strong positive correlations were observed between TGFβ1, TGFβRII and p-SMAD2/3 in tumor tissue, and an inverse correlation was observed between intratumor and plasmatic TGFβ1 levels in TN BCs. In LB-HER2+ tumors, p-SMAD2/3 was associated with older age at diagnosis and inversely correlated with p53 staining and lymph-node metastasis, while tumor-size negatively correlated with TGFβ1 and TGFβRII in this BC subgroup. Also, in p53-negative BCs, tumor size and Ki67 negatively correlated with both TGFβ1, TGFβRII and p-SMAD2/3. No correlation was found between SNPs and TGFβ1-signaling components expression. Conclusion TGFβ1 canonical signaling is activated in approximately half of BCs, and correlation between TGFβ components indicate a paracrine activation, which may exert tumor suppressor effects in p53-negative or Luminal-B-HER2+ subgroups. Transforming growth factor beta Breast neoplasm Immunohistochemistry Biomarkers Prognosis Polymorphisms Surgery Pathology Marla Karine Amarante verfasserin aut Jefferson Crespigio verfasserin aut Bruna Karina Banin Hirata verfasserin aut Nathalia de Sousa Pereira verfasserin aut Karen Brajão de Oliveira verfasserin aut Roberta Losi Guembarovski verfasserin aut Maria Angelica Ehara Watanabe verfasserin aut In Surgical and Experimental Pathology BMC, 2019 4(2021), 1, Seite 13 (DE-627)1040711715 25208454 nnns volume:4 year:2021 number:1 pages:13 https://doi.org/10.1186/s42047-021-00097-0 kostenfrei https://doaj.org/article/8bad43f3d1824ec2b108ab4a5c597844 kostenfrei https://doi.org/10.1186/s42047-021-00097-0 kostenfrei https://doaj.org/toc/2520-8454 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2021 1 13 |
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10.1186/s42047-021-00097-0 doi (DE-627)DOAJ057936544 (DE-599)DOAJ8bad43f3d1824ec2b108ab4a5c597844 DE-627 ger DE-627 rakwb eng RD1-811 RB1-214 Glauco Akelinghton Freire Vitiello verfasserin aut TGFβ1 pathway components in breast cancer tissue from aggressive subtypes correlate with better prognostic parameters in ER-positive and p53-negative cancers 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background TGFβ signaling exerts context-specific effects in breast cancer (BC) pathogenesis and single nucleotide polymorphisms (SNPs) in TGFβ-signaling components play a role in the genetic control of their expression and in BC susceptibility and clinical presentation. However, studies investigating the association between the TGFβ-signaling molecules and BC prognosis rarely considered disease subtypes and SNPs. Therefore, the present study aimed to evaluate the expression of TGFβ-signaling components in BC tissue from patients with available data regarding TGFB1 and TGFBR2 SNPs and plasmatic TGFβ1 levels. Methods Immunostaining for TGFβ1, TGFβRII and phosphorylated (p)-SMAD2/3 was investigated in primary tumor tissue from 34 patients with luminal-B-HER2+ (LB-HER2), HER2-enriched (HER2) and triple negative (TN) BC subtypes genotyped for TGFB1 (rs1800468, rs1800469, rs1800470 and rs1800471) and TGFBR2 (rs3087465) SNPs. Results Strong positive correlations were observed between TGFβ1, TGFβRII and p-SMAD2/3 in tumor tissue, and an inverse correlation was observed between intratumor and plasmatic TGFβ1 levels in TN BCs. In LB-HER2+ tumors, p-SMAD2/3 was associated with older age at diagnosis and inversely correlated with p53 staining and lymph-node metastasis, while tumor-size negatively correlated with TGFβ1 and TGFβRII in this BC subgroup. Also, in p53-negative BCs, tumor size and Ki67 negatively correlated with both TGFβ1, TGFβRII and p-SMAD2/3. No correlation was found between SNPs and TGFβ1-signaling components expression. Conclusion TGFβ1 canonical signaling is activated in approximately half of BCs, and correlation between TGFβ components indicate a paracrine activation, which may exert tumor suppressor effects in p53-negative or Luminal-B-HER2+ subgroups. Transforming growth factor beta Breast neoplasm Immunohistochemistry Biomarkers Prognosis Polymorphisms Surgery Pathology Marla Karine Amarante verfasserin aut Jefferson Crespigio verfasserin aut Bruna Karina Banin Hirata verfasserin aut Nathalia de Sousa Pereira verfasserin aut Karen Brajão de Oliveira verfasserin aut Roberta Losi Guembarovski verfasserin aut Maria Angelica Ehara Watanabe verfasserin aut In Surgical and Experimental Pathology BMC, 2019 4(2021), 1, Seite 13 (DE-627)1040711715 25208454 nnns volume:4 year:2021 number:1 pages:13 https://doi.org/10.1186/s42047-021-00097-0 kostenfrei https://doaj.org/article/8bad43f3d1824ec2b108ab4a5c597844 kostenfrei https://doi.org/10.1186/s42047-021-00097-0 kostenfrei https://doaj.org/toc/2520-8454 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2021 1 13 |
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TGFβ1 pathway components in breast cancer tissue from aggressive subtypes correlate with better prognostic parameters in ER-positive and p53-negative cancers |
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Abstract Background TGFβ signaling exerts context-specific effects in breast cancer (BC) pathogenesis and single nucleotide polymorphisms (SNPs) in TGFβ-signaling components play a role in the genetic control of their expression and in BC susceptibility and clinical presentation. However, studies investigating the association between the TGFβ-signaling molecules and BC prognosis rarely considered disease subtypes and SNPs. Therefore, the present study aimed to evaluate the expression of TGFβ-signaling components in BC tissue from patients with available data regarding TGFB1 and TGFBR2 SNPs and plasmatic TGFβ1 levels. Methods Immunostaining for TGFβ1, TGFβRII and phosphorylated (p)-SMAD2/3 was investigated in primary tumor tissue from 34 patients with luminal-B-HER2+ (LB-HER2), HER2-enriched (HER2) and triple negative (TN) BC subtypes genotyped for TGFB1 (rs1800468, rs1800469, rs1800470 and rs1800471) and TGFBR2 (rs3087465) SNPs. Results Strong positive correlations were observed between TGFβ1, TGFβRII and p-SMAD2/3 in tumor tissue, and an inverse correlation was observed between intratumor and plasmatic TGFβ1 levels in TN BCs. In LB-HER2+ tumors, p-SMAD2/3 was associated with older age at diagnosis and inversely correlated with p53 staining and lymph-node metastasis, while tumor-size negatively correlated with TGFβ1 and TGFβRII in this BC subgroup. Also, in p53-negative BCs, tumor size and Ki67 negatively correlated with both TGFβ1, TGFβRII and p-SMAD2/3. No correlation was found between SNPs and TGFβ1-signaling components expression. Conclusion TGFβ1 canonical signaling is activated in approximately half of BCs, and correlation between TGFβ components indicate a paracrine activation, which may exert tumor suppressor effects in p53-negative or Luminal-B-HER2+ subgroups. |
abstractGer |
Abstract Background TGFβ signaling exerts context-specific effects in breast cancer (BC) pathogenesis and single nucleotide polymorphisms (SNPs) in TGFβ-signaling components play a role in the genetic control of their expression and in BC susceptibility and clinical presentation. However, studies investigating the association between the TGFβ-signaling molecules and BC prognosis rarely considered disease subtypes and SNPs. Therefore, the present study aimed to evaluate the expression of TGFβ-signaling components in BC tissue from patients with available data regarding TGFB1 and TGFBR2 SNPs and plasmatic TGFβ1 levels. Methods Immunostaining for TGFβ1, TGFβRII and phosphorylated (p)-SMAD2/3 was investigated in primary tumor tissue from 34 patients with luminal-B-HER2+ (LB-HER2), HER2-enriched (HER2) and triple negative (TN) BC subtypes genotyped for TGFB1 (rs1800468, rs1800469, rs1800470 and rs1800471) and TGFBR2 (rs3087465) SNPs. Results Strong positive correlations were observed between TGFβ1, TGFβRII and p-SMAD2/3 in tumor tissue, and an inverse correlation was observed between intratumor and plasmatic TGFβ1 levels in TN BCs. In LB-HER2+ tumors, p-SMAD2/3 was associated with older age at diagnosis and inversely correlated with p53 staining and lymph-node metastasis, while tumor-size negatively correlated with TGFβ1 and TGFβRII in this BC subgroup. Also, in p53-negative BCs, tumor size and Ki67 negatively correlated with both TGFβ1, TGFβRII and p-SMAD2/3. No correlation was found between SNPs and TGFβ1-signaling components expression. Conclusion TGFβ1 canonical signaling is activated in approximately half of BCs, and correlation between TGFβ components indicate a paracrine activation, which may exert tumor suppressor effects in p53-negative or Luminal-B-HER2+ subgroups. |
abstract_unstemmed |
Abstract Background TGFβ signaling exerts context-specific effects in breast cancer (BC) pathogenesis and single nucleotide polymorphisms (SNPs) in TGFβ-signaling components play a role in the genetic control of their expression and in BC susceptibility and clinical presentation. However, studies investigating the association between the TGFβ-signaling molecules and BC prognosis rarely considered disease subtypes and SNPs. Therefore, the present study aimed to evaluate the expression of TGFβ-signaling components in BC tissue from patients with available data regarding TGFB1 and TGFBR2 SNPs and plasmatic TGFβ1 levels. Methods Immunostaining for TGFβ1, TGFβRII and phosphorylated (p)-SMAD2/3 was investigated in primary tumor tissue from 34 patients with luminal-B-HER2+ (LB-HER2), HER2-enriched (HER2) and triple negative (TN) BC subtypes genotyped for TGFB1 (rs1800468, rs1800469, rs1800470 and rs1800471) and TGFBR2 (rs3087465) SNPs. Results Strong positive correlations were observed between TGFβ1, TGFβRII and p-SMAD2/3 in tumor tissue, and an inverse correlation was observed between intratumor and plasmatic TGFβ1 levels in TN BCs. In LB-HER2+ tumors, p-SMAD2/3 was associated with older age at diagnosis and inversely correlated with p53 staining and lymph-node metastasis, while tumor-size negatively correlated with TGFβ1 and TGFβRII in this BC subgroup. Also, in p53-negative BCs, tumor size and Ki67 negatively correlated with both TGFβ1, TGFβRII and p-SMAD2/3. No correlation was found between SNPs and TGFβ1-signaling components expression. Conclusion TGFβ1 canonical signaling is activated in approximately half of BCs, and correlation between TGFβ components indicate a paracrine activation, which may exert tumor suppressor effects in p53-negative or Luminal-B-HER2+ subgroups. |
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title_short |
TGFβ1 pathway components in breast cancer tissue from aggressive subtypes correlate with better prognostic parameters in ER-positive and p53-negative cancers |
url |
https://doi.org/10.1186/s42047-021-00097-0 https://doaj.org/article/8bad43f3d1824ec2b108ab4a5c597844 https://doaj.org/toc/2520-8454 |
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Marla Karine Amarante Jefferson Crespigio Bruna Karina Banin Hirata Nathalia de Sousa Pereira Karen Brajão de Oliveira Roberta Losi Guembarovski Maria Angelica Ehara Watanabe |
author2Str |
Marla Karine Amarante Jefferson Crespigio Bruna Karina Banin Hirata Nathalia de Sousa Pereira Karen Brajão de Oliveira Roberta Losi Guembarovski Maria Angelica Ehara Watanabe |
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up_date |
2024-07-03T15:01:02.131Z |
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