Toward the development of a universal grading system for ovarian epithelial carcinoma

Shimizu, Yoshio; Kamoi, Seiryu; Amada, Satoshi; Akiyama, Futoshi; Silverberg, Steven G.

doi:10.1002/(sici)1097-0142(19980301)82:5<893::aid-cncr14>3.0.co;2-w

Cited by 212 publications

(68 citation statements)

References 17 publications

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“…For grading of tumors, the Silverberg grading system, which is composed of architectural, nuclear, and mitotic features, was used. 19 The number of mitoses per 10 high-power fields (HPF) was evaluated and separated into 3 groups, <9 of 10 HPF, 10 to 23 of 10 HPF, and >24 of 10 HPF. For statistical evaluation and survival analysis, only the patients with invasive ovarian carcinomas were included.…”

Section: Study Population and Tissue Samplesmentioning

confidence: 99%

Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancer

Noske

Weichert

Niesporek

et al. 2008

Cancer

199

175

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BACKGROUNDThe human nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 (CRM1) mediates the nuclear export of proteins and messenger RNAs and, thus, is an important regulator of subcellular distribution of key molecules. Whereas cell‐biologic studies have suggested a fundamental role for CRM1 in the regulation of mitosis, the expression of this protein in human tumor tissue has not been investigated to date.METHODSIn this study, the expression of CRM1 was analyzed in a cohort of 88 ovarian tumors and 12 ovarian cell lines for the first time to the authors' knowledge.RESULTSImmunohistochemistry revealed increased nuclear (52.7%) and cytoplasmic (56.8%) expression of CRM1 in 74 carcinomas compared with the expression revealed in borderline tumors and benign lesions. Similarly, CRM1 expression was increased in ovarian cancer cell lines compared with human ovarian surface epithelial cells. Cytoplasmic CRM1 expression was related significantly to advanced tumor stage (P = .043), poorly differentiated carcinomas (P = .011), and higher mitotic rate (P = .008). Nuclear CRM1 was associated significantly with cyclooxygenase‐2 (COX‐2) expression (P = .002) and poor overall survival (P = .01). Because it was demonstrated previously that blocking of CRM1 by leptomycin B (LMB) contributes to the inhibition of nuclear export, the authors used a set of mechanistic assays to study the effects of CRM1 inhibition in cancer cells. Treatment of OVCAR‐3 cells with LMB revealed a significant reduction of cell proliferation and increased apoptosis as well as suppressed interleukin‐1β‐induced COX‐2 expression.CONCLUSIONSThe current results indicated that CRM1 is expressed in a subpopulation of ovarian carcinomas with aggressive behavior and is related to poor patient outcome. A correlation also was demonstrated between CRM1 and COX‐2 expression in ovarian cancer tissue. Furthermore, the treatment of ovarian cancer cells with LMB revealed a reduction in COX‐2 expression. Therefore, the authors suggest that CRM1 may be an interesting biomarker for the assessment of patient prognosis and a molecular target for anticancer treatment. Cancer 2008. © 2008 American Cancer Society.

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Section: Study Population and Tissue Samplesmentioning

confidence: 99%

Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancer

Noske

Weichert

Niesporek

et al. 2008

Cancer

199

175

View full text Add to dashboard Cite

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“…Histology and grade were re-evaluated by an experienced gynecopathologist (CD). Hematoxylin and eosin (H&E)-stained sections were cut from paraffin-embedded blocks and used for histopathological evaluation; grading of tumors was assessed using Silverberg grading system; 24 and staging of tumors was carried out according to the International Federation of Gynecology and Obstetrics (FIGO) staging system.…”

Section: Study Populationmentioning

confidence: 99%

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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“…according to the Silverberg grading system composed of architectural, nuclear and mitotic features. 17 …”

Section: Histopathological Examinationmentioning

confidence: 99%

Expression of mitogen‐activated protein kinase phosphatase‐1 (MKP‐1) in primary human ovarian carcinoma

Denkert

Schmitt

Berger

et al. 2002

Intl Journal of Cancer

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The mitogen-activated protein kinase phosphatase-1, MKP-1 (CL100) is involved in inactivation of MAP-kinase pathways, regulation of stress-responses and suppression of apoptosis. We investigated expression of MKP-1 in 90 cases of primary ovarian tumors, 11 normal ovaries as well as 4 ovarian carcinoma cell lines. Immunohistochemical expression of MKP-1 protein was reduced in tissue from LMP tumors and invasive ovarian carcinomas compared to normal ovaries and cystadenomas. A moderate to strong expression of MKP-1 was detected in 57.6% of invasive ovarian carcinomas. In a descriptive univariate survival analysis, MKP-1 expression was a prognostic marker for shorter progressionfree survival of patients with invasive ovarian carcinomas. Patients with carcinomas positive for MKP-1 had a median progression-free survival of only 18.3 months compared to 40.6 months for patients with carcinomas negative for MKP-1 (log-rank test, p ‫؍‬ 0.019). Other prognostic parameters for progression-free survival were FIGO stage, grade and pT stage. In an exploratory multivariate analysis, we found that MKP-1 expression as well as FIGO stage and grade were independent prognostic factors for progression-free survival. In contrast to progression-free survival, we did not find any influence of MKP-1 expression on patient overall survival. We investigated expression and regulation of MKP-1 mRNA by Northern Blot in vitro using 4 ovarian carcinoma cell lines (SKOV-3, OVCAR-3, CAOV-3, OAW-42). MKP-1 mRNA was inducible by interleukin-1␤ and tumor necrosis factor-␣ in SKOV-3 and OVCAR-3 cells, whereas CAOV-3 and OAW-42 expressed MKP-1 mRNA constitutively. In OVCAR-3 cells MKP-1 mRNA levels were strongly inducible upon treatment of cells with cisplatin. Our data indicate that MKP-1 is expressed in a subset of ovarian carcinomas and regulated by inflammatory mediators. Expression of MKP-1 may be associated with shorter progression-free survival times. Further studies are needed to determine whether MKP-1 expression is a clinically useful marker to estimate patient prognosis as well as the response to chemotherapy.

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Toward the development of a universal grading system for ovarian epithelial carcinoma

Cited by 212 publications

References 17 publications

Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancer

Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancer

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

Expression of mitogen‐activated protein kinase phosphatase‐1 (MKP‐1) in primary human ovarian carcinoma

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