Immunohistochemical expression of POC1A, NUF2, and Ki-67 in invasive ductal carcinoma of the breast

Am J Clin Pathol. 2025 Dec 1;164(6):890-907. doi: 10.1093/ajcp/aqaf114.

Abstract

Objective: Breast cancer is a leading malignancy among women worldwide. Mitotic regulation proteins such as POC1A and NUF2 have been linked to tumor aggressiveness.

Methods: This retrospective study evaluated the immunohistochemical expression of POC1A and NUF2 in 136 cases of invasive ductal carcinoma (IDC), 96 matched metastatic lymph nodes, and 48 adjacent normal breast tissues using Ki-67 as a supporting proliferation marker. Associations with clinicopathologic features were assessed, and survival analyses were conducted using Kaplan-Meier and Cox regression models.

Results: POC1A and NUF2 were significantly overexpressed in tumor tissues compared to normal tissues (P < .001). High expression levels were associated with larger tumor size, higher grade and stage, lymphovascular invasion, distant metastasis, hormone receptor negativity, triple-negative breast cancer (TNBC), and poor Nottingham Prognostic Index scores. Both markers were significantly associated with lymph node involvement. Ki-67 expression also correlated positively with POC1A and NUF2 coexpression (r = 0.574; 95% CI, 0.449-0.677; P < .001). Multivariate analysis identified POC1A as an independent predictor of poor overall survival (OS) (hazard ratio, 2.102; 95% CI, 1.41-3.13; P < .001). Coexpression of POC1A and NUF2 was linked to significantly worse prognosis.

Conclusions: High expression levels of POC1A and NUF2 were significantly associated with aggressive clinicopathologic features and poorer prognosis in IDC. Their correlation with Ki-67 and enrichment in TNBC highlight their potential as prognostic markers and predictors of nodal metastasis. Importantly, POC1A expression was independently associated with worse OS in IDC, including TNBC. While not yet directly actionable, our findings nominate POC1A as a promising independent prognostic biomarker that could potentially refine risk stratification in IDC, particularly for aggressive subtypes like TNBC. However, prospective validation in larger cohorts is mandatory before any clinical application.

Keywords: NUF2; POC1A; invasive ductal carcinoma.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / metabolism
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Carcinoma, Ductal, Breast* / metabolism
  • Carcinoma, Ductal, Breast* / mortality
  • Carcinoma, Ductal, Breast* / pathology
  • Cell Cycle Proteins* / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ki-67 Antigen* / metabolism
  • Middle Aged
  • Prognosis
  • Retrospective Studies

Substances

  • Ki-67 Antigen
  • Biomarkers, Tumor
  • Cell Cycle Proteins