Immunohistochemical analysis of vascular density and area in colorectal carcinoma using different markers and comparison with clinicopathologic prognostic factors

Abstract

Analysis of blood and lymphatic vessel in colorectal cancer is controversial in the literature, possibly due to variations in the methods of analysis. In this study, it was aimed to search for a reliable approach in the quantification of angio- and lymphangiovascular density and area as a prognostic factor and to compare such vessel counts in normal mucosa, adenomas and cancer. A retrospective study was performed on 60 sporadic colorectal cancer, 30 colorectal adenomas, and 10 colorectal non-neoplastic lesions. Archival tissues were submitted to immunohistochemical evaluation using antibodies to CD31, CD34, CD105, VEGF-A, VEGF-C, and D2-40. Microvessel density and total vascular area were determined by computer image analysis and values were compared in the three groups of lesions; the prognostic value of these parameters was evaluated in the group of colorectal cancer. Most markers showed progressive vessel counts from non-neoplastic tissue to carcinoma, both for microvessel density and total vascular area. Only microvessel density determined by CD34 in the central areas of the cancer correlated with recurrence/metastasis (p = 0.04) and survival (p = 0.02). Different methods of quantification (microvessel counting versus estimation of total vascular area), immunohistochemical markers (pan-endothelial marker versus neovessels and lymphatic markers), and areas of analysis (periphery versus inner portions of the lesion) were assessed using image analysis. The results corroborate the increase in vascularization of carcinoma and suggest that microvessel density determined by immunostaining for CD34 in the inner portion of the tumor might represent a prognostically relevant parameter in colorectal cancer.

Evaluating the Expression of CD34 Marker in Colorectal Adenocarcinoma and its Relationship with Clinicopathologic Factors

“…The CD34 expression was correlated with adenomas containing severe dysplasia and large adenomas (more than 1 cm) and the significant association of this marker with tumor grade, lymphovascular invasion and lymph node involvement in colorectal carcinoma were also approved (Qasim et al, 2012). Similarly, in a retrospective study, Moreira et al (2011) evaluated the vascular density through immunohistochemical analysis in colorectal carcinoma and showed that the CD34 expression in the central area, cancer is associated with relapse, metastasis and survival rate. The study showed that the incidence of CD34 in the inner area of colorectal carcinoma tumors has the prognostic value in this cancer.…”

“…The CD34 expression is significantly associated with adenomas containing severe dysplasia and large adenomas (more than 1 cm) (Qasim et al, 2012;Sidney et al, 2014). In many other immunohistochemical studies, the expression of this protein is used as a reliable marker to evaluate cancer tumors including: colon (Moreira et al, 2011;Sidney et al, 2014), blood (Borowitz et al, 1990), liver (Borowitz et al, 1990), penile (Martins et al, 2002), lung (Van de Rijn et al, 1994) and trichilemmal (Chaichamnan et al, 2010) cancers. The studies have shown the correlation between CD34 with many clinicopathologic factors as well as the ability of this marker as a prognostic factor.…”

“…The studies have shown the correlation between CD34 with many clinicopathologic factors as well as the ability of this marker as a prognostic factor. Recently, reports have been published about the presence of CD34+cells at the margins of major salivary glands pleomorphic adenoma (Moreira et al, 2011). However, the relationship between CD34+stromal cells and neoplasms desmoplastic stromal have not been widely and sufficiently studied, particularly in colon carcinoma.…”

Lymphangiogenesis and colorectal cancer

“…Many studies were conducted to determine whether lymphangiogenesis is associated with these genetic alterations. In 2011, Moreia et al23 performed a retrospective study including 10 colorectal non-neoplastic lesions, 30 colorectal adenomas and 60 sporadic CRC tumors and found that LMVD increased significantly and sequentially from non-neoplastic tissues to adenomas and cancerous tumors. Another study showed that LMVD was significantly higher in adenomas from patients with carcinoma than those in patients without cancer 24.…”

Correlation between CD34 Marker and Clinico-Pathologic Characteristics of Gastric Cancer

“…Numerous studies have used the expression of this protein as a reliable marker in cancerous tumors by immunohistochemistry. For example, in GC (Dvorak, 1986;Hayashi, 1975), colon (Moreira et al, 2011;Qasim et al, 2012), liver (Cui et al, 1996), blood (Borowitz et al, 1990) and lung (Van de Rijn et al, 1994), the CD34 expressions have been used for diagnostic examination, as well as the relationship between these markers and clinico-pathologic factors.…”