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USP9X expression correlates with tumor progression and poor prognosis in esophageal squamous cell carcinoma.

Peng J, Hu Q, Liu W, He X, Cui L, Chen X, Yang M, Liu H, Wei W, Liu S, Wang H - Diagn Pathol (2013)

Bottom Line: Interestingly, the most intensive staining for USP9X was usually observed in the basal and lower spinous layers of the esophageal epithelium with precursor lesions which often resulted in the earliest malignant lesion.USP9X expression status was positively associated with both depth of invasion (p = 0.046) and lymph node metastasis (p = 0.032).When adjusted by multivariate analysis, USP9X expression (HR 2.066, P = 0.005), together with TNM stage (HR 1.702, P = 0.042) was an independent predictor for overall survival.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu 610041, China. sunny630@126.com.

ABSTRACT

Background: Ubiquitination is a reversible process of posttranslational protein modification through the action of the family of deubiquitylating enzymes which contain ubiquitin-specific protease 9x (USP9X). Recent evidence indicates that USP9X is involved in the progression of various human cancers. The aim was to detect the expression of USP9X in the progression from normal epithelium to invasive esophageal squamous cell cancer (ESCC) and evaluate the relevance of USP9X expression to the tumor progression and prognosis.

Methods: In this study, USP9X immunohistochemical analysis was performed on tissues constructed from ESCC combined with either normal epithelium or adjacent precursor tissues of 102 patients. All analyses were performed by SPSS 13.0 software.

Results: We observed that the level of high USP9X expression increased gradually in the transformation from normal epithelium (4.0%), to low grade intraepithelial neoplasia (10.5%), then to high grade intraepithelial neoplasia (28.6%), and finally to invasive ESCC (40.2%). The expression of USP9X was found to be significantly different between the normal mucosa and ESCC (P < 0.001), and between low grade intraepithelial neoplasia and high grade intraepithelial neoplasia (p = 0.012). However, no difference was observed between the high expression of USP9X in normal mucosa and low grade intraepithelial neoplasia (P = 0.369), nor between high grade intraepithelial neoplasia and ESCC (p = 0.115). Interestingly, the most intensive staining for USP9X was usually observed in the basal and lower spinous layers of the esophageal epithelium with precursor lesions which often resulted in the earliest malignant lesion. USP9X expression status was positively associated with both depth of invasion (p = 0.046) and lymph node metastasis (p = 0.032). Increased USP9X expression was significantly correlated to poorer survival rate in ESCC patients (p = 0.001). When adjusted by multivariate analysis, USP9X expression (HR 2.066, P = 0.005), together with TNM stage (HR 1.702, P = 0.042) was an independent predictor for overall survival.

Conclusions: Up-regulation of USP9X plays an important role in formation and progression of precancerous lesions in ESCC and USP9X expression levels were significantly correlated with the survival of ESCC patients. Thus, USP9X could be considered as a potential biomarker and prognostic predictor for ESCC.

Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1945302932102737.

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Immunohistochemical staining of USP9X expression in the progression from normal epithelium to ESCC. Paraffin-embedded tissue sections were stained using an immunoperoxidase method, as described in Materials and methods. Representative images (200×) are shown: A In normal esophageal epithelium, immunostaining for weak USP9X signal was found only in the basal layer. B In low grade intraepithelial neoplasia (left side), positive staining was observed in most of the heterogeneous cells from the basal layer to the granular layer of epithelium. The USP9X expression increased gradually in the transformation from low grade intraepithelial neoplasia to high grade intraepithelial neoplasia as carcinoma in situ in which the full-thickness epithelium showed diffuse immunoreactivity for USP9X (right side). C, D In ESCC, intense immunostaining for USP9X was presented in the cytoplasm of most of the cancer cells.
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Figure 1: Immunohistochemical staining of USP9X expression in the progression from normal epithelium to ESCC. Paraffin-embedded tissue sections were stained using an immunoperoxidase method, as described in Materials and methods. Representative images (200×) are shown: A In normal esophageal epithelium, immunostaining for weak USP9X signal was found only in the basal layer. B In low grade intraepithelial neoplasia (left side), positive staining was observed in most of the heterogeneous cells from the basal layer to the granular layer of epithelium. The USP9X expression increased gradually in the transformation from low grade intraepithelial neoplasia to high grade intraepithelial neoplasia as carcinoma in situ in which the full-thickness epithelium showed diffuse immunoreactivity for USP9X (right side). C, D In ESCC, intense immunostaining for USP9X was presented in the cytoplasm of most of the cancer cells.

Mentions: As shown in Figure 1, positive immunostaining for USP9X could be observed in a cytoplasmic pattern. In normal epithelium, weak positive signals were seen only in the basal layer and some of the lower spinous layer in the epithelium, whereas in precursor lesions positive staining was observed in most of the heterogeneous cells of the epithelium (Figure 1A,B). We also noticed that the USP9X expression increased gradually in the transformation from low grade intraepithelial neoplasia to high grade intraepithelial neoplasia as carcinoma in situ in which the full-thickness epithelium showed intensive immunostaining for USP9X (Figure 1B). Moreover, most of ESCC showed diffusely strong positive immunostaining of USP9X (Figure 1C,D).


USP9X expression correlates with tumor progression and poor prognosis in esophageal squamous cell carcinoma.

Peng J, Hu Q, Liu W, He X, Cui L, Chen X, Yang M, Liu H, Wei W, Liu S, Wang H - Diagn Pathol (2013)

Immunohistochemical staining of USP9X expression in the progression from normal epithelium to ESCC. Paraffin-embedded tissue sections were stained using an immunoperoxidase method, as described in Materials and methods. Representative images (200×) are shown: A In normal esophageal epithelium, immunostaining for weak USP9X signal was found only in the basal layer. B In low grade intraepithelial neoplasia (left side), positive staining was observed in most of the heterogeneous cells from the basal layer to the granular layer of epithelium. The USP9X expression increased gradually in the transformation from low grade intraepithelial neoplasia to high grade intraepithelial neoplasia as carcinoma in situ in which the full-thickness epithelium showed diffuse immunoreactivity for USP9X (right side). C, D In ESCC, intense immunostaining for USP9X was presented in the cytoplasm of most of the cancer cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016599&req=5

Figure 1: Immunohistochemical staining of USP9X expression in the progression from normal epithelium to ESCC. Paraffin-embedded tissue sections were stained using an immunoperoxidase method, as described in Materials and methods. Representative images (200×) are shown: A In normal esophageal epithelium, immunostaining for weak USP9X signal was found only in the basal layer. B In low grade intraepithelial neoplasia (left side), positive staining was observed in most of the heterogeneous cells from the basal layer to the granular layer of epithelium. The USP9X expression increased gradually in the transformation from low grade intraepithelial neoplasia to high grade intraepithelial neoplasia as carcinoma in situ in which the full-thickness epithelium showed diffuse immunoreactivity for USP9X (right side). C, D In ESCC, intense immunostaining for USP9X was presented in the cytoplasm of most of the cancer cells.
Mentions: As shown in Figure 1, positive immunostaining for USP9X could be observed in a cytoplasmic pattern. In normal epithelium, weak positive signals were seen only in the basal layer and some of the lower spinous layer in the epithelium, whereas in precursor lesions positive staining was observed in most of the heterogeneous cells of the epithelium (Figure 1A,B). We also noticed that the USP9X expression increased gradually in the transformation from low grade intraepithelial neoplasia to high grade intraepithelial neoplasia as carcinoma in situ in which the full-thickness epithelium showed intensive immunostaining for USP9X (Figure 1B). Moreover, most of ESCC showed diffusely strong positive immunostaining of USP9X (Figure 1C,D).

Bottom Line: Interestingly, the most intensive staining for USP9X was usually observed in the basal and lower spinous layers of the esophageal epithelium with precursor lesions which often resulted in the earliest malignant lesion.USP9X expression status was positively associated with both depth of invasion (p = 0.046) and lymph node metastasis (p = 0.032).When adjusted by multivariate analysis, USP9X expression (HR 2.066, P = 0.005), together with TNM stage (HR 1.702, P = 0.042) was an independent predictor for overall survival.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Genetics, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu 610041, China. sunny630@126.com.

ABSTRACT

Background: Ubiquitination is a reversible process of posttranslational protein modification through the action of the family of deubiquitylating enzymes which contain ubiquitin-specific protease 9x (USP9X). Recent evidence indicates that USP9X is involved in the progression of various human cancers. The aim was to detect the expression of USP9X in the progression from normal epithelium to invasive esophageal squamous cell cancer (ESCC) and evaluate the relevance of USP9X expression to the tumor progression and prognosis.

Methods: In this study, USP9X immunohistochemical analysis was performed on tissues constructed from ESCC combined with either normal epithelium or adjacent precursor tissues of 102 patients. All analyses were performed by SPSS 13.0 software.

Results: We observed that the level of high USP9X expression increased gradually in the transformation from normal epithelium (4.0%), to low grade intraepithelial neoplasia (10.5%), then to high grade intraepithelial neoplasia (28.6%), and finally to invasive ESCC (40.2%). The expression of USP9X was found to be significantly different between the normal mucosa and ESCC (P < 0.001), and between low grade intraepithelial neoplasia and high grade intraepithelial neoplasia (p = 0.012). However, no difference was observed between the high expression of USP9X in normal mucosa and low grade intraepithelial neoplasia (P = 0.369), nor between high grade intraepithelial neoplasia and ESCC (p = 0.115). Interestingly, the most intensive staining for USP9X was usually observed in the basal and lower spinous layers of the esophageal epithelium with precursor lesions which often resulted in the earliest malignant lesion. USP9X expression status was positively associated with both depth of invasion (p = 0.046) and lymph node metastasis (p = 0.032). Increased USP9X expression was significantly correlated to poorer survival rate in ESCC patients (p = 0.001). When adjusted by multivariate analysis, USP9X expression (HR 2.066, P = 0.005), together with TNM stage (HR 1.702, P = 0.042) was an independent predictor for overall survival.

Conclusions: Up-regulation of USP9X plays an important role in formation and progression of precancerous lesions in ESCC and USP9X expression levels were significantly correlated with the survival of ESCC patients. Thus, USP9X could be considered as a potential biomarker and prognostic predictor for ESCC.

Virtual slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1945302932102737.

Show MeSH
Related in: MedlinePlus