High expression of TROP2 correlates with poor prognosis in pancreatic cancer

Abstract

Pancreatic cancer is one of the most devastating human malignancies. Despite considerable research efforts, it remains resistant to almost all available treatment regimens. The human trophoblast cell-surface antigen, TROP2, was found to be strongly expressed in a variety of human epithelial cancers, correlating with aggressiveness and poor prognosis. TROP2 antigen expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumour tissue samples from a series (n=197) of consecutive patients with pancreatic adenocarcinoma. Survival was calculated using Kaplan-Meier curves. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model. TROP2 overexpression was observed in 109 (55%) of 197 pancreatic cancer patients and was significantly associated with decreased overall survival (P<0.01). By univariate analysis, TROP2 overexpression was found to correlate with the presence of lymph node metastasis (P=0.04) and tumour grade (P=0.01). Furthermore, in the subgroup of patients treated surgically with curative intent, TROP2 overexpression significantly correlated with poor progression-free survival (P<0.01). Multivariate analyses revealed TROP2 to be an independent prognosticator. These findings suggest for the first time that TROP2 could be a novel prognostic biomarker for pancreatic cancer. Targeting TROP2 might be a useful treatment approach for patients with pancreatic cancer overexpressing this cell-surface marker.

Figure 1

TROP2 immunostaining in pancreatic tissue, original magnification × 100. (A) TROP2-negative tumour sample (score 0), normal pancreatic tissue (arrow) showing weak (score 2) immunostaining. Pancreatic ductal adenocarcinoma with moderate (score 6) (B) and strong (score 12) (C and D) TROP2 expression, note the TROP2-negative islets of Langerhans (arrow).

Figure 2

Prognostic significance of TROP2 antigen expression in 197 patients with pancreatic ductal adenocarcinomas regarding overall survival as calculated by Kaplan–Meier analysis. Low, patients with tumour (n=88) without TROP2 overexpression; high, patients with tumour (n=109) with TROP2 overexpression. Patients with low TROP2 expression had significantly better overall survival than patients with high TROP2 expression as defined by the log-rank test (P<0.01).

Figure 3

Prognostic significance of TROP2 antigen expression in the subgroup of patients who underwent surgery with curative intent regarding overall (n=134) and progression-free (n=105) survival as calculated by Kaplan–Meier analysis. Patients with tumour tissue presenting TROP2 overexpression (TROP2 high) had a significant shortened overall survival (A) and progression-free (B) interval as compared with patients with tumours lacking TROP2 overexpression (TROP2 low).