Mutation of the nm23 gene, loss of heterozygosity at the nm23 locus and K-ras mutation in ovarian carcinoma: correlation with tumour progression and nm23 gene expression

Mandai, Michiko; Konishi, Ikuo; Komatsu, Takayuki; Mori, Takahide; Arao, Shinji; Nomura, Hiroshi; Kanda, Yusuke; Hayashi, Hiroshi; Fukumoto, Manabu

doi:10.1038/bjc.1995.395

Cited by 32 publications

(23 citation statements)

References 14 publications

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“…Recently, HER2/neu gene ampli®cations has been found to occur only in the subset of ovarian tumors which display LOH of a number of chromosome 17 loci (Papp et al, 1996). In some studies, an increased expression of NME1 has been associated with a more aggressive phenotype (Leary et al, 1995;Mandai et al, 1995;Schneider et al, 1996), although this association remains controversial (Harlozinska et al, 1996). These data are all consistent with the high frequency of LOH chromosome 17 loci harboring these genes in tumors of high grade and stage.…”

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confidence: 77%

Allelotyping defines minimal imbalance at chromosomal region 17q25 in non-serous epithelial ovarian cancers

et al. 2000

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Allelic deletions of multiple chromosome 17q loci in sporadic ovarian cancer of epithelial origin suggest that inactivation of tumor suppressor gene(s) in these regions may be important for ovarian tumorigenesis. To further de®ne the pattern of allelic imbalance in epithelial ovarian tumors of di erent histologies, a PCR-based assay was used to assess loss of heterozygosity (LOH) of polymorphic markers representative of TP53, BRCA1, NME1 and GH1, and region 17q23-25. LOH was observed for at least one marker in 68% of malignant tumors (n=60) and in 18% tumors of borderline malignancy (n=11), but not in benign tumors (n=5). The highest frequency of LOH in malignant tumors (64%) was observed with D17S801 on 17q25. Ten of 39 malignant ovarian tumors displaying LOH of at least one 17q marker, displayed a LOH pattern enabling the determination of a minimal region of overlapping deletion de®ned by D17S795 and D17S801. One borderline tumor also displayed an interstitial LOH pattern that overlapped this 17q25 minimal region of deletion. The histologies of malignant tumors displaying a pattern indicative of interstitial 17q deletions were of the endometrioid, clear cell and mucinous epithelial types. As the minimal region of overlap de®ned by these tumors overlap regions deleted in malignant tumors of all histologic types, and in a tumor of borderline malignancy, the 17q25-tumor suppressor may be implicated in the development of all types of epithelial ovarian tumors.

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confidence: 77%

Allelotyping defines minimal imbalance at chromosomal region 17q25 in non-serous epithelial ovarian cancers

et al. 2000

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“…Although NM23-H2 has been widely investigated as a metastasis suppressor in a great variety of neoplasms, Progesterone-regulated, anti-tumor genes for ovarian cancer V Syed et al studies on OCa are limited. Mandai et al (1995) reported that OCa patients with metastatic lymph node involvement had lower NM23-H2 expression in their cancers than those with lymph node-negative disease. Tas et al (2002) found higher levels of NM23-H2 expression to be associated with better prognosis in OCa patients.…”

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confidence: 99%

Identification of ATF-3, caveolin-1, DLC-1, and NM23-H2 as putative antitumorigenic, progesterone-regulated genes for ovarian cancer cells by gene profiling

et al. 2005

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“…In a stratified univariate analysis and a complete multivariate model of 247 ovarian cancer patients, it was found that nm23 overexpression was an independent predictor of an ominous outcome. 37 Schneider et al 9 demonstrated that nm23 overexpression had a negative impact on prognosis and that the nm23 overexpression was to a wildtype nm23 gene rather than to mutant variants. It is possible that nm23-H1 functions similarly to nm23-H2, which has been shown in vitro to initiate transcription of c-myc, 38 or another related oncogene associated with more malignant phenotypes in human ovarian cancer.…”

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confidence: 99%

NM23 as a prognostic biomarker in ovarian serous carcinoma

Youn

Kim²,

Kim

et al. 2008

Modern Pathology

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The nm23 gene is a reported metastasis suppressor gene. Recent studies have shown that its expression has tissue specificity. The role of nm23 in human ovarian cancer is still controversial. This study examines the prognostic significance of nm23 expression in patients with serous ovarian carcinoma. Following comparative proteomics in 13 fresh frozen ovarian serous cancer tissues with other histological types of ovarian cancers, validation was performed using immunohistochemistry on clinically well-designed 73 ovarian serous carcinoma microarray samples that were retrieved from ovarian cancer patients from 1990 to 2003. Statistical analysis of the results was performed using v 2 test, Cox proportional regression, the Kaplan-Meier method and log-rank test. We found that the expression of nm23 inversely correlated with peritoneal seeding (P ¼ 0.009). However, strong nm23 expression was associated with mortality in patients with ovarian carcinoma in univariate analysis (P ¼ 0.04). Poor prognostic factors of disease-free survival included tumor residue more than 2 cm (P ¼ 0.02), bilaterality (P ¼ 0.01) and peritoneal seeding (Po0.01), whereas poor prognostic factors affecting overall survival included peritoneal seeding (P ¼ 0.05). In Kaplan-Meier analysis, strong nm23 immunoreactivity correlates with poor overall survival (P ¼ 0.04) but not with poor disease-free survival. In conclusion, overexpression of nm23 is independently associated with decreased overall survival in patients with ovarian carcinoma and also significantly correlates with mortality. Nm23 may have a biological function that leads to poor clinical outcomes in ovarian carcinoma.

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Mutation of the nm23 gene, loss of heterozygosity at the nm23 locus and K-ras mutation in ovarian carcinoma: correlation with tumour progression and nm23 gene expression

Cited by 32 publications

References 14 publications

Allelotyping defines minimal imbalance at chromosomal region 17q25 in non-serous epithelial ovarian cancers

Allelotyping defines minimal imbalance at chromosomal region 17q25 in non-serous epithelial ovarian cancers

Identification of ATF-3, caveolin-1, DLC-1, and NM23-H2 as putative antitumorigenic, progesterone-regulated genes for ovarian cancer cells by gene profiling

NM23 as a prognostic biomarker in ovarian serous carcinoma

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