Expression and mutational analysis of Nm23-H1 in liver metastases of colorectal cancer

Heide, I.; Thiede, Christian; Poppe, K; Kant, E. de; Hühn, D; Rochlitz, Christoph

doi:10.1038/bjc.1994.485

Cited by 23 publications

(12 citation statements)

References 22 publications

(23 reference statements)

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“…Loss or gain of function of these genes may cause deregulated c-myc expression [ 14], Since we have studied a number of genet ic alterations in the same collection of métastasés from colorectal cancer before, we analyzed our data on Ki-ras [48], nm23 [49], p53 [29], mdrl, and bcl-2 in the context of the findings on c-myc presented here. No correlation of the c-myc status and expression level or mutations in most of these genes was detected.…”

Section: Discussionmentioning

confidence: 99%

Overexpression and Amplification of c-<i>myc</i> during Progression of Human Colorectal Cancer

1996

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Overexpression and amplification of the c-myc oncogene occur in approximately 70 and 10% of human primary colorectal carcinomas, respectively, indicating the importance of this gene in colorectal tumorigenesis. Little, however, is known about the involvement of c-myc in the progression of colorectal cancer. We therefore determined c-myc gene expression and amplification in a group of primary tumors and metastases from patients with colorectal cancer using quantitative PCR-based tests. While the percentage of metastases over-expressing c-myc (13/26 =50%) was in the same range as reported for primary tumors by others, gene amplification of c-myc was significantly (p = 0.001) more frequent in metastases (16/27 = 59%) compared to primary tumors (1/23 = 4%) in our series. Interestingly, in 23 metastases where both expression and amplification of c-myc could be determined, there was no correlation between gene copy number and expression level (p = 0.18; r = 0.19). We conclude that amplification but not overexpression of c-myc is related to metastatic progression of colorectal cancer and that overexpression of c-myc is driven by mechanisms other than the number of c-myc copies in the tumors studied.

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Section: Discussionmentioning

confidence: 99%

Overexpression and Amplification of c-<i>myc</i> during Progression of Human Colorectal Cancer

1996

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“…Conflicting observations have been reported on the protein level (Ayhan et al, 1993;Haut et al, 1991;Lacombe et al, 1991;Royds et al, 1994;Tannapfel et al, 1995; Yamaguchi et al, 1993;Zeng et al, 1994); on the mRNA level (Haut et al, 1991;Myeroff and Markowitz, 1993; Yamaguchi et al, 1993;Zeng et al, 1994); and on the DNA-level (Bafico et al, 1993; Campo et al, 1994; Cawkwell et al, 1994;Cohn et al, 1991;Heide et al, 1994; lacopetta et al, 1994;Okada et al, 1994;Steeg et al, 1991;Wang et al, 1993;Whitelaw and Northover, 1994).…”

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confidence: 99%

“…Steeg et al (1991) claimed that colorectal cancer provides an example where nm23 mRNA levels remain constant, but allelic deletion is correlated with the development of distant metastasis, and furthermore, that this retained nm23 mRNA level may be explained by the fact that the remaining allele compensates for the lost one. No changes on the nm23-HI DNA level in primary colorectal cancer (Bafico et al, 1993;Cawkwell et al, 1994;Whitelaw and Northover, 1994), or in liver metatases (Heide et al, 1994) Nm23-H1 allelic losses are considered as secondary events, and specific nm23-H 1 mutations have not been observed frequently in colorectal cancer (Bafico et al, 1993. A lateacting suppressor gene at or near the nm23-H1 locus has been suggested (Cohn et al, 1991).…”

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NM-23 H1 immunohistochemistry is not useful as predictor of metastatic potential of colorectal cancer

Lindmark

1996

Br J Cancer

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(Cawkwell et al., 1994;Fearon, 1994). Accumulation of these and other unknown genetic changes is considered to be necessary for tumorigenesis, but none of the known changes can foretell metastatic potential (Fearon, 1994).It was not long ago that the new human potential metastasis-suppressor gene family, 'non-metastatic' nm23, was identified (Steeg et al., 1988). nm23-H1 has been mapped to human chromosome locus 17q21.3-22, and the gene encodes a Mr 17 000 protein of unknown function (Backer et al., 1993;. Potential roles for the nm23 protein have been suggested, such as in the formation of a basement membrane, in tumour differentiation and cell proliferation (Caligo et al., 1995;Howlett et al., 1994;Lombardi et al., 1995).A down-regulated expression of nm23-H 1, on either mRNA and/or protein level, has been reported in various human cancers (some with highly metastatic activities), such as malignant melanoma (Florenes et al., 1992;Xerri et al., 1994) (Nakayama et al., 1993). Similar findings have been reported for breast cancer (Bevilacqua et al., 1989;Hennessy et al., 1991;Hirayama et al., 1991;Royds et al., 1993;Stahl et al., 1991; Tokunaga et al., 1993), although this was not the case in a study by SastreGarau et al. (1992). Mutations and deletions of the nm23 gene have been shown in a number of primary tumours, such as neuroblastomas, lung, breast and renal cancer (Leone et al., , 1993, but not in prostatic cancer (Brewster et al., 1994). Taken together, these results suggest that the nm23 gene may have an important role in the mechanism of metastasis in many solid tumour forms.However, the role of the nm23-H 1 gene in tumour progression and for metastatic potential of colorectal cancer, is not clear. Conflicting observations have been reported on the protein level (Ayhan et al., 1993;Haut et al., 1991;Lacombe et al., 1991;Royds et al., 1994;Tannapfel et al., 1995; Yamaguchi et al., 1993;Zeng et al., 1994); on the mRNA level (Haut et al., 1991;Myeroff and Markowitz, 1993; Yamaguchi et al., 1993;Zeng et al., 1994); and on the DNA-level (Bafico et al., 1993; Campo et al., 1994; Cawkwell et al., 1994;Cohn et al., 1991;Heide et al., 1994; lacopetta et al., 1994;Okada et al., 1994;Steeg et al., 1991;Wang et al., 1993;Whitelaw and Northover, 1994).We have previously explored DNA ploidy, cell proliferative index (Lindmark et al., 1991) and p53 status (Kressner et al., 1996) in colorectal cancer, without being able to detect any substantial correlation to common clinicopathological characteristics and to patient survival time. Nevertheless, continued search for prognostic predictors in colorectal cancer is essential. Thus far, no factors have been identified capable of discriminating between patients truly cured by surgery and patients having subclinical micrometastases in Dukes' stages B and C (Dukes and Bussey, 1958). If such factors were to be available, additional therapy could be offered to selected patients running a high risk for tumour relapse. Furthermore, selected patients could be included in survei...

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“…Moreover, reproducibility of results may vary (13,17,23,29) . Nevertheless, the study of tumor markers in neoplastic tissue is particularly interesting, because it allows analysis of tumor cells and intraindividual biological variability, providing a high degree of biological specificity concerning the cancer under study.…”

Section: Introductionmentioning

confidence: 99%

NM23 protein expression in colorectal carcinoma using TMA (tissue microarray): association with metastases and survival

Oliveira

Neto

Waisberg

et al. 2010

Arq. Gastroenterol.

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-Context -NM23, a metastasis suppressor gene, may be associated with prognosis in patients with colorectal carcinoma.Objective -To analyze NM23 expression and its association with the presence of lymph node and liver metastases and survival in patients operated on for colorectal carcinoma. Methods -One hundred thirty patients operated on for colorectal carcinoma were investigated. Tissue microarray blocks containing neoplastic tissue and tumor-adjacent non-neoplastic mucosa were obtained and analyzed by immunohistochemical staining using a monoclonal anti-NM23 antibody. Immunohistochemical expression was assessed using a semiquantitative scoring method, counting the percentage of stained cells. The results were compared regarding morphological and histological characteristics of the colorectal carcinoma, presence of lymph node and liver metastases, tumor staging, and patient survival. Statistical analysis was performed using the Mann-Whitney test, the Kruskal-Wallis test and Fisher's exact test. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. Results -NM23 expression was higher in colorectal carcinoma tissue than in adjacent non-neoplastic mucosa (P<0.0001). NM23 protein expression did not correlate with degree of cell differentiation (P = 0.57), vascular invasion (P = 0.85), lymphatic invasion (P = 0.41), perineural infiltration (P = 0.46), staging (P = 0.19), lymph node metastases (P = 0.08), or liver metastases (P = 0.59). Disease-free survival showed significant association (P = 0.01) with the intensity of NM23 protein immunohistochemical expression in colorectal carcinoma tissue, whereas overall survival showed no association with NM23 protein expression (P = 0.13). Conclusions -NM23 protein expression was higher in neoplastic colorectal carcinoma tissue than in adjacent non-neoplastic mucosa, showing no correlation with morphological aspects, presence of lymph node or liver metastases, colorectal carcinoma staging, or overall survival. Disease-free survival was higher in patients with increased NM23 expression.

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Expression and mutational analysis of Nm23-H1 in liver metastases of colorectal cancer

Cited by 23 publications

References 22 publications

Overexpression and Amplification of c-<i>myc</i> during Progression of Human Colorectal Cancer

Overexpression and Amplification of c-<i>myc</i> during Progression of Human Colorectal Cancer

NM-23 H1 immunohistochemistry is not useful as predictor of metastatic potential of colorectal cancer

NM23 protein expression in colorectal carcinoma using TMA (tissue microarray): association with metastases and survival

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