p53 gene mutations and protein accumulation in human ovarian cancer.

Kupryjańczyk, Jolanta; Thor, Ann D.; Beauchamp, Roberta L.; Merritt, Victor; Edgerton, Susan M.; Bell, Debra A.; Yandell, David W.

doi:10.1073/pnas.90.11.4961

Cited by 267 publications

(160 citation statements)

References 31 publications

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“…In contrast to previous findings (Kern et al, 1989), when tumours were classified according to their histological stage, a multivariate Cox model analysis showed that p53 mutation, rather than 17p allelic losses, was the only independent prognostic factor (Hamelin et al, 1994). Immunohistochemistry (IHC) studies have indicated that mutated p53 is overexpressed in premalignant head and neck lesions (Shin et al, 1994), oesophageal squamous cell carcinomas (Wagata et al, 1993), ovarian cancer (Kupryjanczyk et al, 1993), breast cancer (Faille et al, 1994) and hepatocellular carcinoma (Wolkmann et al, 1994). In colorectal cancer, overexpression of p53 protein has been correlated with poor short-term prognosis (Yamaguchi et al, 1992; p53 mRNA overexpression in colorectal cancer 529 1 00C 1OC 10 100'…”

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confidence: 68%

Overexpression of p53 mRNA in colorectal cancer and its relationship to p53 gene mutation

el-Mahdani

Vaillant²,

Guiguet³

et al. 1997

Br J Cancer

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We analysed the frequency of p53 mRNA overexpression in a series of 109 primary colorectal carcinomas and its association with p53 gene mutation, which has been correlated with short survival. Sixty-nine of the 109 cases (63%) demonstrated p53 mRNA overexpression, without any correlation with stage or site of disease. Comparison with p53 gene mutation indicated that, besides cases in which p53 gene mutation and p53 mRNA overexpression were either both present (40 cases) or both absent (36 cases), there were also cases in which p53 mRNA was overexpressed in the absence of any mutation (29 cases) and those with a mutant gene in which the mRNA was not overexpressed (four cases). Moreover, the mutant p53 tumours exhibited an increase of p53 mRNA expression, which was significantly higher in tumours expressing the mutated allele alone than in tumours expressing both wild- and mutated-type alleles. These data (1) show that p53 mRNA overexpression is a frequent event in colorectal tumours and is not predictive of the status of the gene, i.e. whether or not a mutation is present; (2) provide further evidence that p53 protein overexpression does not only result from an increase in the half-life of mutated p53 and suggest that inactivation of the p53 function in colorectal cancers involves at least two distinct mechanisms, including p53 overexpression and/or mutation; and (3) suggest that p53 mRNA overexpression is an early event, since it is not correlated with Dukes stage.

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confidence: 68%

Overexpression of p53 mRNA in colorectal cancer and its relationship to p53 gene mutation

el-Mahdani

Vaillant²,

Guiguet³

et al. 1997

Br J Cancer

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“…in ovarian carcinomas (Kupryjańczyk et al, 1993;Casey et al, 1996;DiCioccio et al, 1998;Wen et al, 1999), studies on TP53 status and tumour response to cisplatin-based chemotherapy have not so far given equivocal results (Righetti et al, 1996;de Feudis et al, 1997;Baekelandt et al, 1999;Eisenhauer et al, 1999;Fallows et al, 2001;Reles et al, 2001).…”

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confidence: 99%

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen

et al. 2003

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In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatinbased chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB -IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P ¼ 0.005) or the only (in FIGO IIIC, P ¼ 0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(À) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P ¼ 0.047) and by BCL2 expression in the TP53(À) group (P ¼ 0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P ¼ 0.049); its loss was found with advancing FIGO stage (P ¼ 0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.

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“…These genes include the TP53 tumor suppressor at 17p13 (Marks et al, 1991;Okamoto et al, 1991;Tsao et al, 1991;Eccles et al, 1992;Milner et al, 1993), the HER2/neu oncogene at 17q12 (Slamon et al, 1989), the BRCA1 breast-ovarian cancer susceptibility gene at 17q12 (Miki et al, 1994;Merajver et al, 1995), and the NME1 tumor metastasis marker on 17q21-23 (Viel et al, 1995;Scambia et al, 1996;Schneider et al, 1996). Somatic mutations and increased expression of TP53 have been more often reported in high grade and later stage tumors (Berchuck et al, 1994;Kupryjanczyk et al, 1993). Increased expression of HER2/neu accompanied with or without gene ampli®cation is also a feature of some tumors of high grade and late stage (Slamon et al, 1989).…”

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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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p53 gene mutations and protein accumulation in human ovarian cancer.

Cited by 267 publications

References 31 publications

Overexpression of p53 mRNA in colorectal cancer and its relationship to p53 gene mutation

Overexpression of p53 mRNA in colorectal cancer and its relationship to p53 gene mutation

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen

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

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