Overexpression in metastatic breast cancer supports Syndecan-1 as a marker of invasiveness and poor prognosis

Clin Exp Med. 2023 Sep;23(5):1641-1647. doi: 10.1007/s10238-022-00880-7. Epub 2022 Sep 10.

Abstract

Background: Metastasis is the main cause of breast cancer (BC) mortality. Increasing evidence points to a role of syndecan-1 (CD138) expression as a prognostic marker involved in BC tissue and leptomeningeal metastasis. Aim of this study was to investigate and compare syndecan-1 tissue expression and localization in primary and secondary BC, focusing on brain metastases.

Methods: Syndecan-1 expression was determined by immunohistochemistry. Focal vs diffuse (< or > 50% of cancer cells, respectively) pattern of expression, cellular localization (cytoplasm vs membrane) and intensity of immunostaining on neoplastic cells were evaluated. Moreover, the extent and pattern of expression of syndecan-1 were compared between primary tumors and paired metastases and correlated with the tumor intrinsic subtype.

Results: A total of 23 cases, 10 with paired primary and metastatic tumor and 13 brain metastases, were evaluated. Syndecan-1 was expressed in both primary and metastatic BC. A diffuse cytoplasmic expression was observed in most primary BCs; by contrast, all metastatic lesions showed a membrane pattern of expression, suggesting a shift in cellular localization of syndecan-1 during the metastatic process. Concerning the extent of expression, we observed in metastatic lesions, a trend of association between intrinsic subtypes and extent of positivity. In particular, both BC characterized by overexpression of HER2 and triple-negative tumors were correlated with a diffuse pattern of expression with a moderate to strong intensity.

Conclusion: A diffuse cytoplasmic expression was observed in most primary BCs; by contrast, all metastatic lesions showed a membrane pattern of expression, suggesting a shift in cellular localization of syndecan-1 during the metastatic process.

Keywords: Brain metastases; Breast cancer; Membrane localization; Metastatic process; Syndecan-1 expression.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms*
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Prognosis
  • Syndecan-1 / metabolism

Substances

  • Biomarkers, Tumor
  • Syndecan-1
  • SDC1 protein, human