Carotid artery plaque echomorphology and its association with histopathologic characteristics.

OBJECTIVE: The aim of the study was to determine the association of ultrasonic texture features (severity of stenosis, grey scale median, plaque area, juxtaluminal black area [JBA], and discrete white areas) previously shown to be independent predictors for stroke with established histologic features of plaque instability. METHODS: A cross-sectional study was performed involving 70 patients scheduled for carotid endarterectomy. Before surgery, carotid plaque texture features were obtained with ultrasound after normalization using commercially available software (LifeQ Medical, Nicosia, Cyprus). After carotid endarterectomy, histologic features (number of macrophages [CD68 staining], severity of angiogenesis [CD31 staining], smooth muscle cell [SMC] numbers, size of lipid core, thickness of the fibrous cap, presence of intraplaque hemorrhage, plaque rupture, and instability) also were studied. RESULTS: Symptomatic (n = 20) and asymptomatic (n = 50) patients were comparable in terms of internal carotid stenosis (mean stenosis, 86%; range, 60%-99%) and prevalence of risk factors except for total cholesterol (which was higher in the symptomatic group; P = .023). A low grey scale median and the presence of discrete white areas were associated with an increased number of macrophages (P < .001 and P < .001, respectively), increased neovascularization (P = .019 and P < .001, respectively), larger lipid core (P = .001 and P = .025, respectively), intraplaque hemorrhage presence (P = .001 and P = .001, respectively), plaque rupture (P = .001 and P = .025, respectively), and a decreased number of SMCs (P = .003 and P = .003, respectively). The presence of JBA was associated with a decreased number of SMCs (P = .042), larger lipid core (P = .013), and plaque rupture (P = .002). The combination of a thin fibrous cap with either a large lipid core or plaque rupture was associated with the highest (65%) prevalence of a JBA. Plaque area was not associated with any of the histologic features. After adjusting statin therapy for symptoms, statins were associated with a decreased number of macrophages (P = .038), decreased neovascularization (P = .019), and an increased number of SMCs (P = .023). CONCLUSIONS: A number of ultrasonic texture features previously shown to be independent predictors of stroke have been found to have a strong association with established histologic features of plaque instability. This finding provides insight into the mechanism of ultrasonic texture features in stroke prediction and validates the use of ultrasound in stroke risk stratification.

Differential immunohistochemical expression of CD44s, E-cadherin and ß-catenin among hyperplastic and neoplastic lesions of the prostate gland.

INTRODUCTION: CD44s, E-cadherin and ß-catenin are cell adhesion molecules (CAMs) and appear to influence organ development, inflammation, cancer invasion and metastasis. We studied the expression of these CAMs in prostate cancer (PCa), high-grade prostatic intraepithelial neoplasia (HGPIN) and nodular adenomatous hyperplasia (NH). MATERIALS AND METHODS: 135 paraffin blocks of radical prostatectomy specimens were assessed. CAMs were determined by immunohistochemistry. All sections included PCa, HGPIN and NH. The expression was semiquantitatively evaluated in three scores (1+, 2+, 3+). The markers' immunopositivity was statistically investigated with Gleason score and TNM stage. RESULTS AND CONCLUSIONS: CD44s had score 3+ in 41.5, 46.7 and 37.8% of areas with NH, HGPIN and PCa, respectively. E-cadherin immunostaining was highly detected in 71.1, 78.5 and 63.0% of NH, HGPIN and PCa areas while ß-catenin score 3+ was exclusively membranous in 80.7% of NH and nuclear/cytoplasmic in 70.4 and 48.9% of HGPIN and PCa areas. No marker related to the Gleason score (p = 0.352). CD44s and E-cadherin expression was inversely associated with TNM stage (p = 0.021 and p = 0.042, respectively); no such association was observed for ß-catenin (p = 0.556). The decreased expression of CD44s and E-cadherin is probably associated with the invasive potential of PCa. The ß-catenin staining pattern in neoplastic lesions, either preinvasive or invasive, differs from that in non-neoplastic prostate lesions.

Association between periodontal disease and vulnerable plaque morphology in patients undergoing carotid endarterectomy.

BACKGROUND: Periodontal disease (PD) is a chronic inflammatory oral condition with potentially important systemic sequelae. We sought to determine whether the presence of PD in patients with severe carotid disease was associated with morphological features consistent with carotid plaque instability. METHODS: A total of 52 dentate patients hospitalized for carotid endarterectomy (CEA) had standardized assessments of their periodontal status, including measurements of probing pocket depth (PPD), clinical attachment level (CAL) and bleeding on probing (BoP). Carotid plaque morphology was assessed by ultrasound using the gray scale median (GSM) score and by immunohistochemistry using anti-CD68 and anti-alpha-actin antibodies, markers for macrophages and smooth muscle cells (SMCs) respectively. RESULTS: In total 30/52 patients (58%) had PD. Significant associations were noted between low GSM on ultrasound and each mm in PPD (p = 0.001), each mm in CAL (p = 0.002) and with a 10% increase in BoP (p = 0.009). Using the standardized PERIO definition the association remained robust (aOR = 10.4 [95% CI:2.3-46.3], p = .002). Significant associations were also observed with high macrophage accumulation and each individual PD measure (p < 0.01 for PPD, CAL and BoP) and with the PERIO definition (aOR = 15 [95% CI:1.8-127.8], p = .01). Similarly, low SMC density was also significantly associated with individual measures of PD (p < 0.05 for PPD, CAL and BoP), but not with the PERIO definition (aOR 3.4 [95% CI:0.9-12.8], p = .07). CONCLUSIONS: The presence of PD was significantly associated with both ultrasound and immunohistochemistry features of carotid plaque instability in patients undergoing CEA.

Macrophage infiltration and smooth muscle cells content associated with haptoglobin genotype in human atherosclerotic carotid plaques.

We assessed the association between the haptoglobin (Hp) genotype and 2 common indicators of atherosclerotic plaque instability: macrophage infiltration and the smooth muscle cell (SMC) content. A total of 70 consecutive patients who underwent carotid endarterectomy were included in the study. For immunohistochemical study the anti-CD68 and anti-a-actin antibodies were used on adjacent serial sections; 36 plaques from patients with the Hp 1-1 or 2-1 genotype and 34 plaques from patients with the Hp 2-2 genotype were analyzed. The macrophage content (CD68+) was significantly higher in the Hp 2-2 group compared with that in the Hp 1-1 or 2-1 group (P < .001). In plaques from patients with diabetes, the SMC content was significantly lower in the Hp 2-2 group (P = .034). Carotid plaques from diabetic patients with Hp 2-2 genotype had higher macrophage infiltration and lower SMC content. Both parameters are indicators of atherosclerotic plaque instability.