Microvascular density and endothelial area correlate with Ki-67 proliferative index in surgically-treated pancreatic ductal adenocarcinoma patients

Abstract

Abstract. Previous experimental and clinical data have indicated that tumour cell proliferation is associated with angiogenesis; in addition, an increased microvascular density (MVD) of tumours has been associated with poor prognosis in solid and haematological malignancies. However, limited data exists regarding the association between tumour cell proliferation and angiogenesis in primary tumour tissue from pancreatic ductal adenocarcinoma (PDAC) patients; therefore, the present study aimed to investigate this association. A series of 31 PDAC patients with stage Tumour (T) [2][3] Node (N) 0-1 Metastasis (M) 0 were recruited into the present study and subsequently underwent surgery. PDAC tissue and adjacent normal tissue (ANT), resected during surgery, were evaluated using immunohistochemistry and image analysis methods to determine MVD, endothelial area (EA) and Ki-67 expression, which is an indicator of cell proliferation rate. The results demonstrated a correlation between the above parameters with each other as well as the main clinico-pathological features of PDAC. Significant differences were identified in MVD, EA and Ki-67 proliferation index between PDAC and ANT. It was demonstrated that MVD, EA and Ki-67 proliferation index were significantly correlated with each other in tumour tissue (r=0.69-0.81; P=0.001-0.003). However, no other significant correlations were identified. These data therefore suggested that angiogenesis and cell proliferation rate were significantly increased in PDAC compared with ANT, which provides a biological basis for the potential use of novel combinations of angiogenesis inhibitors and anti-proliferative chemotherapeutic drugs in the treatment of PDAC.

Effective encapsulation and biological activity of phosphorylated chemotherapeutics in calcium phosphosilicate nanoparticles for the treatment of pancreatic cancer

“…This demonstrates that in mice treated with AP-targeted FdUMP-CPSNPs, FdUMP was internalized and released into PDAC tumor cells and that the biological activity of FdUMP against TS was retained. Consistent with the reduced TS levels, tumor staining for Ki-67, a nuclear protein which serves as an index of proliferation (45), also was significantly reduced in mice treated with AP-targeted FdUMP-CPSNPs (Figure 8B). These results are in keeping with other recent data showing that the CCKBR AP increased fluorescent CPSNP accumulation in PDAC tumors in vivo compared to both untargeted or G16-targeted particles (19).…”

CD163 as a marker of M2 macrophage, contribute to predict aggressiveness and prognosis of Kazakh esophageal squamous cell carcinoma

“…In human cancer tissues, the most common method for semiquantitative evaluation of angiogenesis is to measure microvessel density (MVD) using endothelial markers [23], and which is recognized as one of the most useful prognostic markers for tumor progression and survival in multitudinous cancer patients [24–26]. In this study, CD34 as marker of endothelial cells was used to assess MVD in ESCC tissues.…”

Angiogenesis in pancreatic ductal adenocarcinoma: A controversial issue

“…Different studies have demonstrated a relationship between microvascular density (MVD), tumor VEGF-A levels, and disease progression in PDAC [ 6 – 10 ]. The functional analysis of the tumor vasculature has demonstrated that vessels appear collapsed as a consequence of high interstitial pressure with a low delivery of small molecules [ 1 , 4 ].…”