Neuroendocrine Breast Carcinomas Share Prognostic Factors with Gastroenteropancreatic Neuroendocrine Tumors: A Putative Prognostic Role of Menin, p27, and SSTR-2A

Oncology. 2019;96(3):147-155. doi: 10.1159/000493348. Epub 2018 Oct 3.

Abstract

Objectives: Due to the rarity of breast carcinomas with neuroendocrine features (NEBC), the knowledge on their biology is very limited but the identification of their biology and prognostic factors is essential to evaluate both pathogenesis and possible targeted treatment options. We assessed the expression of the well-characterized prognostic factors of gastroenteropancreatic neuroendocrine tumors (GEP-NET) in NEBC.

Methods: We assessed the immunohistochemical expression of neuron-specific enolase (NSE), thymidylate synthase (TS), p27, CD56, menin, and somatostatin receptor type 2A (SSTR-2A) in a series of 36 NEBC and 45 invasive ductal carcinomas (IDC).

Results: Nuclear and cytoplasmic TS, nuclear and cytoplasmic NSE, and nuclear p27 had significant overexpression in NEBC compared with IDC (for all, p < 0.01). In NEBC, cytoplasmic SSTR-2A expression was associated with excellent distant disease-free survival (p = 0.013), cytoplasmic menin expression with poorer relapse-free survival (p = 0.022), and nuclear p27 with longer breast cancer-specific survival (p = 0.022).

Conclusions: There is a striking similarity in GEP-NET and NEBC regarding prognostic factors. GEP-NET and NEBC also appear to show similar expression patterns of the studied markers, while there are notable differences compared to IDC. Due to the wide expression of SSTR-2A, the treatment option with somatostatin analogs in NEBC should be evaluated.

Keywords: Immunohistochemistry; Menin; Neuroendocrine breast carcinoma; Somatostatin receptor; p27.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / biosynthesis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Neuroendocrine / metabolism*
  • Carcinoma, Neuroendocrine / pathology
  • Cyclin-Dependent Kinase Inhibitor p27 / biosynthesis*
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Intestinal Neoplasms / metabolism*
  • Intestinal Neoplasms / pathology
  • Middle Aged
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / pathology
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Proto-Oncogene Proteins / biosynthesis*
  • Receptors, Somatostatin / biosynthesis*
  • Retrospective Studies
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Thymidylate Synthase / biosynthesis

Substances

  • Biomarkers, Tumor
  • CDKN1B protein, human
  • MEN1 protein, human
  • Proto-Oncogene Proteins
  • Receptors, Somatostatin
  • Cyclin-Dependent Kinase Inhibitor p27
  • somatostatin receptor 2
  • Thymidylate Synthase

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor