Overexpression of caspase-3 in hepatocellular carcinomas

Persad, Rajendra; Liu, Chen; Wu, Tsung–Teh; Houlihan, Patrick S.; Hamilton, Stanley R.; Diehl, Anna Mac; Rashid, Asif

doi:10.1038/modpathol.3800146

Cited by 94 publications

(65 citation statements)

References 31 publications

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“…Though caspase-3 is one of the most important molecules in the apoptosis cascade, studies of it in terms of lung cancer outcome have been limited. Several studies of caspase-3 expression have shown conflicting effects on survival [48][49][50]. Our study indicates that the total amount of caspase-3 expression was important for its function in NSCLC tissues, although the activity of the protein remains unclear.…”

mentioning

confidence: 71%

A multiple marker analysis of apoptosis-associated protein expression in non-small cell lung cancer in a Chinese population

Fan

Xu²,

Lin³

et al. 2011

Folia Histochem Cytobiol.

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mentioning

confidence: 71%

A multiple marker analysis of apoptosis-associated protein expression in non-small cell lung cancer in a Chinese population

Fan

Xu²,

Lin³

et al. 2011

Folia Histochem Cytobiol.

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“…Overexpression of CASP3 has also been reported in hepatocellular carcinomas. 39 Coexistence of high levels of CASP3 or CASP8 and BIRC5 or XIAP has been described in other tumor cell lines and tissues. 40 Thus, our data showed IAPs and CASP3, being functionally adversarial molecules, could be coexpressed at higher levels in urothelial carcinoma than in normal urothelium as well.…”

Section: Discussionmentioning

confidence: 98%

Survivin nuclear labeling index: a superior biomarker in superficial urothelial carcinoma of human urinary bladder

Chen

Zhang

et al. 2006

Modern Pathology

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The caspase family proteases are key proapoptotic proteins while the inhibitor of apoptosis proteins (IAP) prevent apoptosis by antagonizing the caspases or other key proapoptotic proteins. Limited studies of IAPs suggested their deregulation contributed to urothelial neoplasia. However, the expression status and biologic or prognostic significance of the caspase and IAP family proteins in urothelial neoplasms is not clear. In the present study, we first systematically evaluated the expression profile of the major apoptosis regulators, including caspases (CASP3,6,7,8,9,10,and 14), IAPs (survivin/BIRC5, CIAP1, CIAP2, XIAP, and LIVIN), APAF1, SMAC, and BCL2, as well as proliferation markers Ki67 and PHH3, in Ta/T1 human urinary bladder urothelial carcinomas and normal urothelium samples by immunohistochemistry. The analysis showed that survivin/ BIRC5 nuclear labeling index (BIRC5-N), but not cytoplasmic staining, was the only apoptotic marker which correlated significantly with tumor grade, stage, and patient outcome. We further analyzed the prognostic value of BIRC5-N in 101 Ta/T1 urinary bladder urothelial carcinomas by univariate analysis, which showed that BIRC5-N as well as the more classical prognosticators (stage, grade, and Ki67 index) were of prognostic significance. However, multivariate analysis by Cox proportional hazard regression demonstrated BIRC5-N was a stronger prognosticator than tumor grade, stage, and Ki67 labeling index. BIRC5-N index of 8% or more predicted unfavorable disease-specific survival (relative risk (RR) ¼ 6.6, 95% confidence interval ¼ 1.6-26.7, P ¼ 0.0080) as well as progression-free survival (RR ¼ 4.4, 95% confidence interval ¼ 1.3-14.6, P ¼ 0.0151). We conclude that BIRC5-N is a superior biologic and prognostic marker for Ta/T1 urothelial carcinomas of urinary bladder.

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“…Similarly, lower expression of caspase 3 has been previously reported as present in less differentiated prostate adenocarcinomas [23] . Conversely, Persad et al [24] showed increased expression of caspase 3 in 52% of resected HCC samples, a distinguishing feature from the surrounding non-HCC tissue. The results from our study, presented herein, probably reflect a larger sample of poorly differentiated HCC with a higher proportion of caspase 3 loss.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemistry panel segregates molecular types of hepatocellular carcinoma in Brazilian autopsy cases

Felipe-Silva¹,

Wakamatsu²,

Cirqueira³

et al. 2016

WJG

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AIM:To assess the distribution of proteins coded by genes reported as relevant for the molecular classification of hepatocellular carcinoma (HCC). METHODS:In this retrospective cross-sectional study, the following clinicopathological data were analyzed in 80 autopsied HCC patients: sex, age, ethnicity, alcohol intake, infection with hepatitis B and/or C virus, infection with human immunodeficiency virus, prior treatment, basic and immediate causes of death, liver weight, presence of cirrhosis, number and size of nodules, gross pattern, histological grade and variants, architectural pattern, invasion of large veins, and presence and location of extrahepatic metastases. The protein products of genes known to be involved in molecular pathogenesis of HCC, including epidermal growth factor receptor (EGFR), MET, keratin 19 (K19), vimentin, beta-catenin, mechanistic target of rapamycin (mTOR), extracellular signaling-related RESULTS:Infection with hepatitis C virus was identified in 49% of the 80 autopsy patients, cirrhosis in 90%, advanced tumors in 95%, and extrahepatic metastases in 38%. Expression of K19, p53 and ERK1 correlated to high-grade lesions. Expression of ERK1, nuclear beta-catenin, cyclin D1 and ERK2 correlated to higher rates of cell proliferation as determined by Ki67. Expression of MET, EGFR (> 0) and caspase 3 correlated with lower histological grades. Expression of EGFR correlated to that of caspase 3, and overexpression of EGFR (≥ 200/300) was observed in low-grade tumors more frequently (grades 1 and 2: 67% vs grade 3: 27% and grade 4: 30%). Expression of ERK1 was associated with that of K19 and vimentin, whereas expression of ERK2 was associated with that of cyclin D1, MET and membrane beta-catenin. Expression of vimentin was strongly correlated with that of K19. CONCLUSION:Expression of K19, p53, ERK1, ERK2, vimentin and nuclear beta-catenin was related to highergrade markers, as opposed to expression/overexpression of EGFR, MET and caspase 3.

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Overexpression of caspase-3 in hepatocellular carcinomas

Cited by 94 publications

References 31 publications

A multiple marker analysis of apoptosis-associated protein expression in non-small cell lung cancer in a Chinese population

A multiple marker analysis of apoptosis-associated protein expression in non-small cell lung cancer in a Chinese population

Survivin nuclear labeling index: a superior biomarker in superficial urothelial carcinoma of human urinary bladder

Immunohistochemistry panel segregates molecular types of hepatocellular carcinoma in Brazilian autopsy cases

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