Ki-67 and ProExC are useful immunohistochemical markers in esophageal squamous intraepithelial neoplasia

Wang, Wen Chuang; Wu, Tsung Teh; Chandan, Vishal S.; Lohse, Christine M.; Zhang, Lizhi

doi:10.1016/j.humpath.2010.12.009

Cited by 36 publications

(31 citation statements)

References 30 publications

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“…Wang et al . showed that Ki67 and ProExC exhibited high sensitivity and specificity for distinguishing reactive hyperplasia from LGIN and HGIN [50]. In this study, we found that c-Jun, cystatin A, involucrin and SPRR3 expressed exclusively in the basal layer, are detected in all epidermal layers, but low in LGIN and HGIN.…”

Section: Discussionsupporting

confidence: 53%

Differentiation-Associated Genes Regulated by c-Jun and Decreased in the Progression of Esophageal Squamous Cell Carcinoma

Luo

et al. 2014

PLoS ONE

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Transcription factor c-Jun plays a key role in controlling epithelium cell proliferation, apoptosis and differentiation. However, molecular mechanism and biological functions of c-Jun in squamous differentiation and the progression of esophageal squamous cell carcinoma (ESCC) remain elusive. In this study, we found that c-Jun bound directly to the promoter region, and activated the transcription of differentiation-associated genes including cystatin A, involucrin and SPRR3 in vivo. Ectopic expression of c-Jun enhanced SPRR3 transactivation in KYSE450 cells. Conversely, TAM67, a dominant negative mutant of c-Jun, inhibited SPRR3 transactivation. c-Jun increased expression of SPPR3 mainly via a PKC/JNK pathway in response to TPA in KYSE450 cells. Furthermore, c-Jun was remarkably reduced in esophageal cancer. Interestingly, cystatin A, involucrin and SPRR3 were significantly downregulated as well, and associated with differentiation grade. Expression of c-Jun was correlated with the expression of these genes in normal epithelium and ESCC. Importantly, the expression of these genes was remarkably decreased during the malignant transformation from normal epithelium to low-grade intraepithelial neoplasia (LGIN) or high-grade intraepithelial neoplasia (HGIN). The expression of cystatin A and involucrin was significantly reduced from LGIN to HGIN. These results suggest c-Jun was involved in the regulation of differentiation-associated genes in ESCC. These genes might serve as the potential markers in distinguishing normal epithelium from esophageal squamous intraepithelial neoplasia.

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Section: Discussionsupporting

confidence: 53%

Differentiation-Associated Genes Regulated by c-Jun and Decreased in the Progression of Esophageal Squamous Cell Carcinoma

Luo

et al. 2014

PLoS ONE

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“…Compared with other quantification methods, such as calculating percentage of immunoreactive cells [27], advantages of the method are speed, ease, and reproducibility. ProExC expression as a cell-proliferation marker was reported to show a similar pattern to that of Ki-67 in LIN, HIN, and CIS [31].…”

Section: Discussionmentioning

confidence: 79%

“…Thus, the up-regulation of CK14 in an early phase of esophageal carcinogenesis may be associated with increased cell proliferation, failure of terminal differentiation, and oncogenic aberration. We adopted a quantification method for Ki-67 positivity in esophageal SIN focusing on height of staining within the squamous epithelium, in accordance with a recent study [31], with some modification. Compared with other quantification methods, such as calculating percentage of immunoreactive cells [27], advantages of the method are speed, ease, and reproducibility.…”

Section: Discussionmentioning

confidence: 99%

Stepwise overexpression of p63, p53, and cytokeratin 14 during progression of esophageal squamous intraepithelial neoplasia: useful immunohistochemical markers for differential diagnosis

et al. 2011

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Background Esophageal squamous intraepithelial neoplasia (ESIN) as a precursor for invasive carcinoma is classified into low-grade IN (LIN) and high-grade IN (HIN), the latter including carcinoma in situ (CIS). Increasing grades of ESIN are associated with increasing risk of invasive carcinoma, but differentiation among LIN, HIN, and CIS is subjective and challenging. As p63, a member of the p53 family, is known to regulate differentiation and proliferation in epithelial progenitor cells, its expression, along with that of cytokeratin (CK) 14 (basal squamous marker) and Ki-67 (proliferation marker), might be of diagnostic assistance. Methods Immunohistochemical staining was performed on endoscopically resected specimens from 69 patients (73 lesions) with ESIN between 2008 and 2010. Specimens having no atypical cells distant from ESIN were defined as negative for IN (NIN). Results There were 13 LIN, 29 HIN, and 31 CIS lesions. The size of CIS (mean 20.1 mm) was significantly larger than that of HIN (14.3 mm) or LIN (10.0 mm). Immunolabeling scores (ILS) for p63, p53, CK14, and Ki-67 showed stepwise increase with ESIN progression (NIN vs. LIN and LIN vs. HIN, P \ 0.05-0.0001; HIN vs. CIS, P \ 0.05-0.001). Mean total ILSs of all four markers were 2.0 for NIN, 4.3 for LIN, 7.4 for HIN, and 9.1 for CIS (P \ 0.0001). A cutoff value for total ILS of B5 versus C6 demonstrated highest sensitivity (96.0%) and specificity (85.7%) in distinguishing HIN from LIN.Conclusions This study suggests that p63 and p53 are coordinately upregulated in esophageal squamous carcinogenesis, and assessment of their expression might provide a useful adjunct tool for differential diagnosis of ESIN.

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“…11,12 Intermediate and strong Ki-67 staining is highly sensitive and specific in distinguishing reactive or hyperplastic squamous epithelium from squamous IN. Immunohistochemistry of p53 protein expression showed high specificity but low sensitivity in distinguishing reactive hyperplasia from squamous IN.…”

Section: Differential Diagnosis and Pitfalls With Respect To Squamous Inmentioning

confidence: 99%

Histopathological diagnoses of squamous intraepithelial neoplasia, carcinoma in situ and early invasive cancer of the oesophagus: the Japanese viewpoint

Arai

Matsuda

Nishimura

et al. 2015

Diagnostic Histopathology

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Ki-67 and ProExC are useful immunohistochemical markers in esophageal squamous intraepithelial neoplasia

Cited by 36 publications

References 30 publications

Differentiation-Associated Genes Regulated by c-Jun and Decreased in the Progression of Esophageal Squamous Cell Carcinoma

Differentiation-Associated Genes Regulated by c-Jun and Decreased in the Progression of Esophageal Squamous Cell Carcinoma

Stepwise overexpression of p63, p53, and cytokeratin 14 during progression of esophageal squamous intraepithelial neoplasia: useful immunohistochemical markers for differential diagnosis

Histopathological diagnoses of squamous intraepithelial neoplasia, carcinoma in situ and early invasive cancer of the oesophagus: the Japanese viewpoint

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