Intratumoral α-SMA enhances the prognostic potency of CD34 associated with maintenance of microvessel integrity in hepatocellular carcinoma and pancreatic cancer

PLoS One. 2013 Aug 5;8(8):e71189. doi: 10.1371/journal.pone.0071189. Print 2013.

Abstract

Microvessel density (MVD) as an angiogenesis predictor is inefficient per se in cancer prognosis. We evaluated prognostic values of combining intratumoral alpha-smooth muscle actin (α-SMA)-positive stromal cell density and MVD after curative resection in hypervascular hepatocellular carcinoma (HCC) and hypovascular pancreatic cancer (PC). Tissue microarrays were constructed from tumors of 305 HCC and 57 PC patients who underwent curative resection and analyzed for α-SMA and CD34 expression by immunostaining. Prognostic values of these two proteins and other clinicopathological features were examined. Both low α-SMA density and high MVD-CD34 were associated in HCC with the presence of intrahepatic metastasis and microvascular invasion, and they were related to lymph node involvement and microvascular invasion in PC (p<0.05). Although CD34 alone, but not α-SMA, was an independent prognostic factor for overall survival and recurrence-free survival, the combination of low α-SMA and high CD34 was a predictor of worst prognosis for both types of tumors and had a better power to predict patient death and early recurrence (p<0.01). Furthermore, the results show that distribution of most of the α-SMA-positive cells and vascular endothelial cells overlap, showing major colocalization on vascular walls. Poor microvessel integrity, as indicated by high MVD, together with low perivascular α-SMA-positive cell coverage is associated with early recurrence, unfavorable metastasis, and short survival after tumor resection. This finding highlights the significance of vascular quality in tumor progression, which provides an optimized complement to vascular quantity in prognosis of postoperative patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Antigens, CD34 / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Cell Count
  • Cohort Studies
  • Humans
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Microvessels / pathology*
  • Pancreatic Neoplasms / blood supply
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Predictive Value of Tests
  • Prognosis
  • Survival Analysis
  • Tissue Array Analysis

Substances

  • ACTA2 protein, human
  • Actins
  • Antigens, CD34
  • Biomarkers, Tumor

Grant support

Supported by the National Natural Science Foundation of China (81172005 and 81172276), the National Natural Science Foundation of Shanghai (11ZR1407000), Ph.D. Programs Foundation of Ministry of Education of China (20110071120096), and the Chinesisch-Deutsches Forschungsprojekt (GZ 857). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.