Immunohistochemical staining for DNA topoisomerase II-alpha in benign, premalignant, and malignant lesions of the prostate

Willman, Joseph H.; Holden, Joseph A.

doi:10.1002/(sici)1097-0045(20000301)42:4<280::aid-pros5>3.0.co;2-p

Cited by 34 publications

(21 citation statements)

References 25 publications

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“…15,16 Similar to our finding of a significant inverse correlation of Top IIa expression and survival, other groups have detected an unfavorable prognostic impact of Top IIa expression in ovarian cancer as well as in other series of neoplasms, such as breast cancer, synovial sarcoma, lung cancer and endometrial carcinoma. 20,[36][37][38][39][40] One explanation for the shorter survival rate associated with elevated Top IIa levels could be an enhancement of tumor cell proliferation, which results in an increased tumor aggressiveness.…”

Section: Discussionsupporting

confidence: 85%

“…13,14 Top IIa expression, genetic alteration and enzyme activity have been studied in malignancies of different types. [15][16][17][18][19][20] However, earlier studies investigated Top IIa mRNA expression using frozen tissues as it had been expected that formalin fixation and paraffin embedding result in fragmentation of nucleic acids and chemical modification by protein-protein and protein-nucleic acid cross-links, making RNA extracted from such processed tissues unsuitable for molecular analysis techniques. Nevertheless, recent studies have proved the reliable gene expression measurement of RNA isolated from formalin-fixed paraffin-embedded (FFPE) tissues.…”

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confidence: 99%

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Topoisomerase IIα mRNA and protein expression in ovarian carcinoma: correlation with clinicopathological factors and prognosis

et al. 2009

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Topoisomerase IIa (Top IIa) is a nuclear enzyme that plays a central role in DNA metabolism, and is a molecular target for a variety of chemotherapeutic agents. Top IIa has recently gained attention as a biomarker for therapy response and patient survival. In this study, we attempted to assess the feasibility of measuring Top IIa gene expression in RNA, isolated from archival formalin-fixed paraffin-embedded tissue specimens, which are used routinely in pathology laboratories. We have employed a new technique on the basis of magnetic particles' separation and purification of nucleic acids, and evaluated both protein and mRNA expressions from the same routinely processed tissue blocks. We investigated the expression of Top IIa mRNA and protein by real-time reverse transcription polymerase chain reaction and immunohistochemistry, in a cohort of 133 primary ovarian carcinomas, and evaluated the association between Top IIa expression and clincopathological variables as well as patient outcome. Elevated Top IIa mRNA expression was observed in high-grade tumors (P ¼ 0.003) and advanced stage disease (P ¼ 0.011). In univariate Kaplan-Meier analysis, patients with higher expression of Top IIa nuclear protein had a significantly decreased overall survival (P ¼ 0.045). Interestingly, we detected cytoplasmic protein expression of Top IIa in a subset of samples. Cytoplasmic expression of Top IIa was associated with the expression of chromosomal region maintenance/exportin 1 (CRM1)-a nuclear export protein (P ¼ 0.008). Our study suggests that Top IIa overexpression is involved in the progression of ovarian cancer in a subset of the patients. Our results encourage the further evaluation of the prognostic and predictive values of Top IIa expression in ovarian carcinoma, which might help to assess the patients' risk profile, and the planning of an individualized therapy.

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Section: Discussionsupporting

confidence: 85%

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confidence: 99%

Topoisomerase IIα mRNA and protein expression in ovarian carcinoma: correlation with clinicopathological factors and prognosis

et al. 2009

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“…High-grade prostatic intraepithelial neoplasia (HG-PIN) and invasive prostatic adenocarcinoma are neoplastic proliferations with similar, but not identical, histochemical, immunophenotypic, and genotypic features, [1][2][3][4][5][6][7] as well as gene expression profiles. 8 In addition, HG-PIN, especially cribriform and flat HG-PIN, can mimic invasive prostatic adenocarcinoma and immunohistochemistry may be needed to document the presence of basal cells in the former.…”

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confidence: 91%

Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade prostatic intraepithelial neoplasia

Hameed

Humphrey

2006

Modern Pathology

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Typically glands of prostatic adenocarcinoma have a single cell lining, although stratification can be seen in invasive carcinomas with a cribriform architecture, including ductal carcinoma. The presence and diagnostic significance of stratified cells within non-cribriform carcinomatous prostatic glands has not been well addressed. The histomorphological features and immunohistochemical profile of cases of non-cribriform prostatic adenocarcinoma with stratified malignant glandular epithelium were analyzed. These cases were identified from needle biopsy cases from the consultation files of one of the authors and from a review of 150 consecutive in-house needle biopsy cases of prostatic adenocarcinoma. Immunohistochemistry was performed utilizing antibodies reactive against high molecular weight cytokeratin (34bE12), p63 and a-methylacylcoenzyme-A racemase (AMACR). A total of 8 cases were identified, including 2 from the 150 consecutive inhouse cases (1.3%). In 4 cases, the focus with glands having stratified epithelium was the sole carcinomatous component in the biopsy, while such a component represented 5-30% of the invasive carcinoma seen elsewhere in the remaining cases. The main attribute in all these foci was the presence of glandular profiles lined by several layers of epithelial cells with cytological and architectural features resembling flat or tufted high-grade prostatic intraepithelial neoplasia, but lacking basal cells as confirmed by negative 34bE12 and/or p63 immunostains in all cases. The AMACR staining profile of the stratified foci was variable, with 4 foci showing positivity, and 3 foci being negative, including two cases that displayed AMACR positivity in adjacent non-stratified prostatic adenocarcinoma. Prostatic adenocarcinoma with stratified malignant glandular epithelium can be identified in prostate needle biopsy samples harboring non-cribriform prostatic adenocarcinoma and resembles glands with high-grade prostatic intraepithelial neoplasia. These 'PIN-like' carcinomas can present in pure form. Recognition of this pattern of prostatic adenocarcinoma is necessary to correctly diagnose such cases as invasive carcinoma.

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“…1,[99][100][101][102] For example, the frequent 8p12-21 allelic loss commonly found in prostate cancer was also found in microdissected PIN. 99 Other examples of genetic changes found in carcinoma that already exist in PIN include loss of heterozygosity (LOH) at 8p22, 12pter-p12, 10q11.2, 21,99 and gain of chromosomes 7, 8, 10, and 12.…”

Section: Genetic and Molecular Changesmentioning

confidence: 99%

High-grade prostatic intraepithelial neoplasia

2004

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High-grade prostatic intraepithelial neoplasia (PIN) is now accepted as the most likely preinvasive stage of adenocarcinoma, almost two decades after its first formal description. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent invasive carcinoma. The only method of detection is biopsy; PIN does not significantly elevate serum prostate-specific antigen (PSA) concentration or its derivatives and cannot be detected by current imaging techniques, including ultrasound. Most patients with PIN will develop carcinoma within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype, which are similar to cancer rather than normal prostatic epithelium, indicating impairment of cell differentiation with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.

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Immunohistochemical staining for DNA topoisomerase II-alpha in benign, premalignant, and malignant lesions of the prostate

Cited by 34 publications

References 25 publications

Topoisomerase IIα mRNA and protein expression in ovarian carcinoma: correlation with clinicopathological factors and prognosis

Topoisomerase IIα mRNA and protein expression in ovarian carcinoma: correlation with clinicopathological factors and prognosis

Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade prostatic intraepithelial neoplasia

High-grade prostatic intraepithelial neoplasia

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