Immunohistochemically detectable p53 and mdm-2 oncoprotein expression in colorectal carcinoma: prognostic significance

Öfner, Dietmar; Maier, Hans; Riedmann, B; Holzberger, Peter T.; Nogler, M; Tötsch, Martin; Bànkfalvi, Àgnes; Winde, G; Böcker, W.; Schmid, K. W.

doi:10.1136/mp.48.1.m12

Cited by 22 publications

(17 citation statements)

References 12 publications

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“…The same authors also showed that both nuclear and p53 protein expression appeared to be important in a multivariate analysis (Sun et al, 1993). A further study (Ofner et al, 1995) showed that there was no relationship between p53 protein expression and grade or stage parameters, such as Dukes' stage, in colorectal cancer. This finding has been reiterated (Mulder et al, 1995) in a study of 109 colorectal cancers.…”

Section: Discussionmentioning

confidence: 92%

p53 and Rb1 protein expression: are they prognostically useful in colorectal cancer?

Poller

Baxter²,

Shepherd³

1997

Br J Cancer

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Section: Discussionmentioning

confidence: 92%

p53 and Rb1 protein expression: are they prognostically useful in colorectal cancer?

Poller

Baxter²,

Shepherd³

1997

Br J Cancer

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“…In immunohistochemical studies using monoclonal anti-MDM2 protein antibody, the incidence of MDM2 immunohistochemical (over)expression in human cancers has been reported to be 30% in bladder cancers (Lianes et al, 1994), 20% in colorectal cancers (Ofner et al, 1995), 3% in ovarian cancers (Foulkes et al, 1995), 40% in oral carcinoma (Matsumura et al, 1996) and 22-41% in breast cancers (Marchetti et al, 1995b;McCann et al, 1995). In NSCLC, whereas Marchetti et al (1995a) reported that MDM2 oncogene product expression was detected immunohistochemically only in three (6%) patients with gene amplification, it was detected in the present study in 24% of patients, independently of MDM2 gene amplification status.…”

Section: Post-operative Prognosismentioning

confidence: 99%

“…Incubation with the primary antibodies (monoclonal MDM2 antibody, IF-2, Oncogene Science, USA, and monoclonal p53 antibody, DO-7, Novocastra Laboratories, UK), British Journal of Cancer (1997) 75(9), [1302][1303][1304][1305][1306][1307][1308] . Cancer Research Campaign 1997 the enzyme colour reaction, haematoxylin counterstaining and mounting were carried out as described elsewhere (Foulkes et al, 1995;Marchetti et al, 1995a and b;McCann et al, 1995;Ofner et al, 1995;Matsumura et al, 1996). Immunostaining results were assessed, taking into account the cancer cells whose nuclei showed positive immunoreactivity for MDM2 ( Figure 1) or p53 protein.…”

Section: Immunohistochemical Analysismentioning

confidence: 99%

“…Before staining, sections were pretreated with microwave irradiation for antigen retrieval, as described previously (Cattoretti et al, 1992;Marchetti et al, 1995b;McCann et al, 1995;Ofner et al, 1995). Incubation with the primary antibodies (monoclonal MDM2 antibody, IF-2, Oncogene Science, USA, and monoclonal p53 antibody, DO-7, Novocastra Laboratories, UK), British Journal of Cancer (1997) 75(9), [1302][1303][1304][1305][1306][1307][1308] .…”

Section: Immunohistochemical Analysismentioning

confidence: 99%

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MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation

Higashiyama

Doi²,

Kodama³

et al. 1997

Br J Cancer

125

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Summary MDM2 is an oncoprotein that inhibits p53 tumour-suppressor protein. Amplification of the MDM2 gene and overexpression of its protein have been observed in some human malignancies, and these abnormalities have a role in tumorigenesis through inactivation of p53 function. To determine the clinicopathological and prognostic value of MDM2 abnormalities in non-small-cell lung cancer (NSCLC), MDM2 gene amplification and its protein expression status were analysed in surgically resected materials. MDM2 gene amplification was detected in only 2 (7%) of the 30 tested patients. MDM2 protein was found immunohistochemically in a total of 48 (24%) of the 201 patients. MDM2 protein was slightly frequently observed in patients with adenocarcinoma, but its presence or absence was not associated with clinicopathological factors such as T-factor, N-factor, stage, tumour size, differentiation or p53 protein status. Overall, MDM2-positive patients tended to have a better prognosis (P = 0.062). In particular, among immunohistochemically p53-negative patients (n = 110), those with positive MDM2 protein expression showed significantly better prognosis (P = 0.039) and, in a multivariate analysis, MDM2 protein status was a favourable prognostic factor (P = 0.037). In contrast, among p53-positive patients (n = 91), there was no difference in prognosis depending on MDM2 protein status. Thus, in the NSCLC patients studied, MDM2 gene amplification was a minor event, but expression of its protein, which was often observed immunohistochemically, was a favourable prognostic marker, especially among patients without p53 protein accumulation. Further study is needed to determine how MDM2 protein expression results in a better prognosis.Keywords: MDM2 gene; non-small-cell lung cancer; p53; prognosis; immunohistochemistry; amplification; fluorescence-based polymerase chain reaction single-strand conformation polymorphism The MDM2 gene was originally identified and cloned by amplification in a transformed tumorigenic Balb/c 3T3 fibroblast cell line (Cahilly-Snyder et al, 1987;Fakharzadeh et al, 1991;Oliner et al, 1992). Its product, p90, is now considered to form a tight complex with both the wild-type and mutant p53 tumour-suppressor gene protein and to inactivate wild-type p53 function by masking the Nterminal acidic transactivating domain of p53 protein, indicating that abnormalities of the MDM2 gene may be closely associated with tumorigenesis and/or tumour development (Olson et al, 1993; Haines et al, 1994). Indeed, MDM2 gene amplification and overexpression of its product have been described in several types of malignancies in humans. However, the clinicopathological role of these abnormalities has yet to be determined.In lung cancer, p53 abnormalities have been well examined but, to our knowledge, MDM2 abnormalities in this disease have been reported only by Marchetti et al (1995a

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“…In the study by MildeLangosch et al, (1995) on vulvar cancer, loss of p53 function was associated with a high risk of progression and an unfavourable prognosis. In the literature the prognostic value of p53 seems to be controversial, because in some studies p53 is considered prognostic relevant (Charpin et al, 1995;Esrig et al, 1994;Florenes et al, 1994;Shurbaji et al, 1995;Sun et al, 1992;Vogt et al, 1997), whereas in other studies it is not King et al, 1996;Ofner et al, 1995;Xerri et al, 1994;Younes et al, 1995). It may be that the prognostic value of p53 depends on whether mutation of p53 occurs during carcinogenesis, progression or metastasis of the tumour.…”

Section: Discussionmentioning

confidence: 95%

In squamous cell carcinoma of the vulva, overexpression of p53 is a late event and neither p53 nor mdm2 expression is a useful marker to predict lymph node metastases

et al. 1999

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SummaryTo offer more tailored treatment to individual patients with squamous cell carcinoma of the vulva, more accurate prediction of lymph node metastases is required. As p53 and mdm2 are genes known to be involved in the development of other tumours, we studied expression of p53 and mdm2 in carcinogenesis of squamous cell carcinoma of the vulva and their clinical relevance. Archival material of 141 T1 and T2 vulvar tumours were used. Of the 141 primary tumours, the corresponding 39 lymph node metastases (LNM) were studied, and in 90 cases the pre-existent epithelia adjacent to the tumour (EAT) and in 14 cases vulvar intraepithelial neoplasia adjacent to the tumour (VIN) was also investigated. Detection of p53 and mdm2 protein was immunohistochemically performed. Scoring categories were: negative (1); weakly positive (2); moderately to markedly positive (3); and markedly positive (4). Overexpression of p53 was seen in 56% of the LNM, 39% of the primary tumours, 21% of the VIN lesions and 0% in the group of EAT. No relation was found between overexpression of p53 in the primary tumour and LNM. Expression of mdm2 was seen in 14% of the primary tumours, of which four cases were marked positive. In the group of LNM no mdm2-positive staining was observed. In the group of EAT, 25% was mdm2-positive, of which six cases were marked positive. In the group of VIN, 36% showed moderate (score 3) mdm2 expression. No relation was found between expression of mdm2 and LNM. In squamous cell carcinoma, overexpression of p53 is a late event in carcinogenesis. Marked expression of mdm2 is rarely seen in vulvar carcinomas, indicating that aberrant p53 cannot induce mdm2 expression. LNM cannot be predicted by detection of these proteins.

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Immunohistochemically detectable p53 and mdm-2 oncoprotein expression in colorectal carcinoma: prognostic significance

Cited by 22 publications

References 12 publications

p53 and Rb1 protein expression: are they prognostically useful in colorectal cancer?

p53 and Rb1 protein expression: are they prognostically useful in colorectal cancer?

MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation

In squamous cell carcinoma of the vulva, overexpression of p53 is a late event and neither p53 nor mdm2 expression is a useful marker to predict lymph node metastases

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