Limits...
Leukemia inhibitory factor receptor is a novel immunomarker in distinction of well-differentiated HCC from dysplastic nodules.

Luo Q, Zhang Y, Wang N, Jin G, Jin H, Gu D, Tao X, Huo X, Ge T, Cong W, Wang C, Qin W - Oncotarget (2015)

Bottom Line: However, sensitivity or specificity of the individual marker is still limited.In addition, colony formation assay was used to explore the role of LIFR in tumorigenesis.Silencing of LIFR could significantly promote colony formation of HCC cells, whereas ectopic overexpression of LIFR resulted in impaired ability of colony formation of HCC cells.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT
Differential diagnosis of well-differentiated hepatocellular carcinoma (WD-HCC) and high-grade dysplastic nodules (HGDNs) represents a challenge for pathologists. Several immunohistochemistry markers have been identified to distinguish hepatocellular carcinoma (HCC) from HGDNs. However, sensitivity or specificity of the individual marker is still limited. In this study, we analyzed dynamic alteration of leukemia inhibitory factor receptor (LIFR) and CD34 during hepatocarcinogenesis from dysplastic nodules to small HCC. The diagnostic performance of LIFR and CD34 combination in WD-HCC and HGDNs was investigated by logistic regression models and validated in an independent validation cohort. LIFR was decreased and CD34 was increased along with stepwise progression of hepatocarcinogenesis from low-grade dysplastic nodules (LGDNs) to small HCC. The sensitivity and specificity of the LIFR and CD34 combination for WD-HCC detection were 93.5% and 90.5%, respectively. In addition, colony formation assay was used to explore the role of LIFR in tumorigenesis. Silencing of LIFR could significantly promote colony formation of HCC cells, whereas ectopic overexpression of LIFR resulted in impaired ability of colony formation of HCC cells. These findings indicate that LIFR and CD34 combination may be used as an available differential diagnostic model for WD-HCC from HGDNs in clinical practice.

Show MeSH

Related in: MedlinePlus

Representative images of HE staining and immunohistochemical staining of LIFR and CD34 in LGDN, HGDN, WD-sHCC, and MD-sHCC(A) Typical HE-stained images for LGDN (n = 25), HGDN (n = 21), WD-sHCC (n = 31), and MD-sHCC (n = 19). (B) Immunostaining of LIFR in LGDN, HGDN, WD-sHCC, and MD-sHCC. (C) Immunostaining scores distribution of LIFR expression. (D) Immunohistochemical expression of LIFR in LGDN, HGDN, WD-sHCC, and MD-sHCC. A scatter plot of IOD for LIFR was obtained from tissue microarray. (E) Immunostaining of CD34 in LGDN, HGDN, WD-sHCC, and MD-sHCC. (F) Immunoreaction score distribution of CD34. (G) A scatter plot of IOD for CD34 was obtained from tissue microarray.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4466664&req=5

Figure 4: Representative images of HE staining and immunohistochemical staining of LIFR and CD34 in LGDN, HGDN, WD-sHCC, and MD-sHCC(A) Typical HE-stained images for LGDN (n = 25), HGDN (n = 21), WD-sHCC (n = 31), and MD-sHCC (n = 19). (B) Immunostaining of LIFR in LGDN, HGDN, WD-sHCC, and MD-sHCC. (C) Immunostaining scores distribution of LIFR expression. (D) Immunohistochemical expression of LIFR in LGDN, HGDN, WD-sHCC, and MD-sHCC. A scatter plot of IOD for LIFR was obtained from tissue microarray. (E) Immunostaining of CD34 in LGDN, HGDN, WD-sHCC, and MD-sHCC. (F) Immunoreaction score distribution of CD34. (G) A scatter plot of IOD for CD34 was obtained from tissue microarray.

Mentions: Because differential diagnosis between HGDN and WD-sHCC based on morphologic characteristics alone is very difficult for pathologists, we further classified our specimens into LGDN (n = 25), HGDN (n = 21), WD-sHCC (n = 31), and MD-sHCC (n = 19). Representative images of HE and LIFR staining were shown in Figure 4A–4B. The negative immunoreactivity was demonstrated in 24% of LGDN, 9.52% of HGDN, 58.06% of WD-sHCC and 42.11% of MD-sHCC (Figure 4C). Decreased level of LIFR in WD-sHCC compared with HGDN was also confirmed based on analysis of IOD (Figure 4D, P = 0.0011).


Leukemia inhibitory factor receptor is a novel immunomarker in distinction of well-differentiated HCC from dysplastic nodules.

Luo Q, Zhang Y, Wang N, Jin G, Jin H, Gu D, Tao X, Huo X, Ge T, Cong W, Wang C, Qin W - Oncotarget (2015)

Representative images of HE staining and immunohistochemical staining of LIFR and CD34 in LGDN, HGDN, WD-sHCC, and MD-sHCC(A) Typical HE-stained images for LGDN (n = 25), HGDN (n = 21), WD-sHCC (n = 31), and MD-sHCC (n = 19). (B) Immunostaining of LIFR in LGDN, HGDN, WD-sHCC, and MD-sHCC. (C) Immunostaining scores distribution of LIFR expression. (D) Immunohistochemical expression of LIFR in LGDN, HGDN, WD-sHCC, and MD-sHCC. A scatter plot of IOD for LIFR was obtained from tissue microarray. (E) Immunostaining of CD34 in LGDN, HGDN, WD-sHCC, and MD-sHCC. (F) Immunoreaction score distribution of CD34. (G) A scatter plot of IOD for CD34 was obtained from tissue microarray.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4466664&req=5

Figure 4: Representative images of HE staining and immunohistochemical staining of LIFR and CD34 in LGDN, HGDN, WD-sHCC, and MD-sHCC(A) Typical HE-stained images for LGDN (n = 25), HGDN (n = 21), WD-sHCC (n = 31), and MD-sHCC (n = 19). (B) Immunostaining of LIFR in LGDN, HGDN, WD-sHCC, and MD-sHCC. (C) Immunostaining scores distribution of LIFR expression. (D) Immunohistochemical expression of LIFR in LGDN, HGDN, WD-sHCC, and MD-sHCC. A scatter plot of IOD for LIFR was obtained from tissue microarray. (E) Immunostaining of CD34 in LGDN, HGDN, WD-sHCC, and MD-sHCC. (F) Immunoreaction score distribution of CD34. (G) A scatter plot of IOD for CD34 was obtained from tissue microarray.
Mentions: Because differential diagnosis between HGDN and WD-sHCC based on morphologic characteristics alone is very difficult for pathologists, we further classified our specimens into LGDN (n = 25), HGDN (n = 21), WD-sHCC (n = 31), and MD-sHCC (n = 19). Representative images of HE and LIFR staining were shown in Figure 4A–4B. The negative immunoreactivity was demonstrated in 24% of LGDN, 9.52% of HGDN, 58.06% of WD-sHCC and 42.11% of MD-sHCC (Figure 4C). Decreased level of LIFR in WD-sHCC compared with HGDN was also confirmed based on analysis of IOD (Figure 4D, P = 0.0011).

Bottom Line: However, sensitivity or specificity of the individual marker is still limited.In addition, colony formation assay was used to explore the role of LIFR in tumorigenesis.Silencing of LIFR could significantly promote colony formation of HCC cells, whereas ectopic overexpression of LIFR resulted in impaired ability of colony formation of HCC cells.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT
Differential diagnosis of well-differentiated hepatocellular carcinoma (WD-HCC) and high-grade dysplastic nodules (HGDNs) represents a challenge for pathologists. Several immunohistochemistry markers have been identified to distinguish hepatocellular carcinoma (HCC) from HGDNs. However, sensitivity or specificity of the individual marker is still limited. In this study, we analyzed dynamic alteration of leukemia inhibitory factor receptor (LIFR) and CD34 during hepatocarcinogenesis from dysplastic nodules to small HCC. The diagnostic performance of LIFR and CD34 combination in WD-HCC and HGDNs was investigated by logistic regression models and validated in an independent validation cohort. LIFR was decreased and CD34 was increased along with stepwise progression of hepatocarcinogenesis from low-grade dysplastic nodules (LGDNs) to small HCC. The sensitivity and specificity of the LIFR and CD34 combination for WD-HCC detection were 93.5% and 90.5%, respectively. In addition, colony formation assay was used to explore the role of LIFR in tumorigenesis. Silencing of LIFR could significantly promote colony formation of HCC cells, whereas ectopic overexpression of LIFR resulted in impaired ability of colony formation of HCC cells. These findings indicate that LIFR and CD34 combination may be used as an available differential diagnostic model for WD-HCC from HGDNs in clinical practice.

Show MeSH
Related in: MedlinePlus