Expression of E-, P- and N-Cadherin and Its Clinical Significance in Cervical Squamous Cell Carcinoma and Precancerous Lesions

<div><p>Aberrant expression of classical cadherins has been observed in tumor invasion and metastasis, but its involvement in cervical carcinogenesis and cancer progression is not clear. We investigated E-, P- and N-cadherin expression and its significance in cervical squamous cell carcinoma (SCC) and cervical intraepithelial neoplasia (CIN). This retrospective study enrolled 508 patients admitted to Women's Hospital, School of Medicine, Zhejiang University with cervical lesions between January 2006 and December 2010. Immunochemical staining was performed in 98 samples of normal cervical epithelium (NC), 283 of CIN, and 127 of early-stage SCC. The association of cadherin staining with clinical characteristics and survival of the patients was evaluated by univariate and multivariate analysis. We found gradients of decreasing E-cadherin expression and increasing P-cadherin expression from NC through CIN to SCC. Aberrant E-cadherin and P-cadherin expression were significantly associated with clinical parameters indicating poor prognosis and shorter patient survival. Interestingly, we found very low levels of positive N-cadherin expression in CIN and SCC tissues that were not related to CIN or cancer. Pearson chi-square tests showed that E-cadherin expression in SCC was inversely correlated with P-cadherin expression (E-P switch), and was not correlated with N-cadherin expression. More important, patients with tissues exhibiting an E-P switch in expression had highly aggressive phenotypes and poorer prognosis than those without E-P switch expression. Our findings suggest that E-cadherin and P-cadherin, but not N-cadherin staining, might be useful in diagnosing CIN and for predicting prognosis in patients with early-stage SCC.</p></div

Expression of E-, P- and N-cadherin in Normal Cervical Epithelium, CIN and Early-stage Cervical Squamous Cell Carcinoma.

<p>Expression of E-, P- and N-cadherin in Normal Cervical Epithelium, CIN and Early-stage Cervical Squamous Cell Carcinoma.</p

Representative immunohistochemical staining showing E-, P- and N-cadherin expression in normal cervical (NC) epithelium, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (SCC) tissue using serial section technique.

<p>Simultaneously reduced E-cadherin expression, increased P-cadherin expression and negative N-cadherin expression were observed in one representative case with CIN (B) or SCC tissue (C). One representative case with NC tissue (simultaneously increased E-cadherin expression, reduced P-cadherin expression and negative N-cadherin expression) was shown as a control (A). Magnifications, ×200.</p

Univariate and Multivariate Analysis of the Associations between Prognostic Value and Disease-free and Overall Survival Rates in Patients of Early-stage Cervical Squamous Cell Cancer.

<p>Univariate and Multivariate Analysis of the Associations between Prognostic Value and Disease-free and Overall Survival Rates in Patients of Early-stage Cervical Squamous Cell Cancer.</p

The Correlation of the E-P switch and several clinical variables.

<p>Among 127 early-stage SCC patients, 17 presented with simultaneously reduced E-cadherin expression and increased P-cadherin expression (an E-P switch). The E-P switch was significantly associated with endometrial extension (<i>P</i> = 0.003), lymph vascular space invasion (LVSI) (<i>P</i> = 0.027), surgical margin (<i>P</i> = 0.036), and lymph node metastasis (LNM) (<i>P</i> = 0.001).</p

The Correlation of P-cadherin or N-cadherin with E-cadherin Expression in Early-stage Cervical Squamous Cell Carcinoma.

<p>The Correlation of P-cadherin or N-cadherin with E-cadherin Expression in Early-stage Cervical Squamous Cell Carcinoma.</p

The Correlation between Expression of Classical Cadherins and Clinicopathological Characteristics in Patients with Early-stage Cervical Squamous Cell carcinomaCharacteristics.

<p>The Correlation between Expression of Classical Cadherins and Clinicopathological Characteristics in Patients with Early-stage Cervical Squamous Cell carcinomaCharacteristics.</p

Kaplan–Meyer curves showing the association of aberrant expression of E-cadherin, P-cadherin, N-cadherin, and the E-P switch with patient disease-free survival (DFS) and overall survival (OS).

<p>Reduced E-cadherin (A) and increased P-cadherin expression (B), as well as the E-P switch (D), were significantly associated with shorter DFS and OS. N-cadherin expression was not significantly associated with DFS or OS (C).</p

Simultaneous Enantioselective Determination of the Chiral Fungicide Prothioconazole and Its Major Chiral Metabolite Prothioconazole-Desthio in Food and Environmental Samples by Ultraperformance Liquid Chromatography–Tandem Mass Spectrometry

An efficient and sensitive chiral analytical method was established for the determination of the chiral fungicide prothioconazole and its major chiral metabolite prothioconazole-desthio in agricultural and environmental samples using ultraperformance liquid chromatography–tandem mass spectrometry. The optical rotation and absolute configuration of enantiomers were identified by optical rotation detector and electronic circular dichroism spectra. The elution order of prothioconazole and its chiral metabolite enantiomers was <i>R</i>-(+)-prothioconazole-desthio, <i>S</i>-(−)-prothioconazole-desthio, <i>R</i>-(−)-prothioconazole, and <i>S</i>-(+)-prothioconazole. The mean recoveries from the samples was 71.8–102.0% with intraday relative standard deviations (RSDs) of 0.3–11.9% and interday RSDs of 0.9–10.6%. The formation of prothioconazole-desthio was studied in soil under field conditions and enantioselective degradation was observed for chiral prothioconazole. Remarkable enantioselective degradation was observed: <i>R</i>-prothioconazole degraded preferentially with EF values from 0.48 to 0.37. Although prothioconazole-desthio is the most remarkably bioactive metabolite, no obvious enantioselective behavior was observed in soil. These results may help to systematically evaluate prothioconazole and its metabolites in food and environmental safety