Surgical and Experimental Pathology (Sep 2021)

TGFβ1 pathway components in breast cancer tissue from aggressive subtypes correlate with better prognostic parameters in ER-positive and p53-negative cancers

  • Glauco Akelinghton Freire Vitiello,
  • Marla Karine Amarante,
  • Jefferson Crespigio,
  • Bruna Karina Banin Hirata,
  • Nathalia de Sousa Pereira,
  • Karen Brajão de Oliveira,
  • Roberta Losi Guembarovski,
  • Maria Angelica Ehara Watanabe

DOI
https://doi.org/10.1186/s42047-021-00097-0
Journal volume & issue
Vol. 4, no. 1
pp. 1 – 13

Abstract

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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.

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