p53 In tumour pathology: Can we trust immunohistochemistry?—revisited!

Hall, Peter A.; Lane, David P.

doi:10.1002/path.1711720103

Cited by 548 publications

(337 citation statements)

References 16 publications

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“…Of particular note was that immunohistochemically detected p53 protein expression did not necessarily indicate the presence of p53 genetic mutations. The pattern of immunohistochemical expression of p53 protein, the proportion of p53-positive cells, should be crucial in discussing the relationship between p53 immunoreactivity and genetic mutation (Hall and Lane, 1994). For example, focal (heterogeneous) expression, the occurrence of dispersed positive cells, does not seem to correlate with the obvious abnormality of p53 gene (Baas et al, 1994;Shiao et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that the mean TS mRNA level in gastric cancers is 1.6-to 1.7-fold higher than that in colorectal cancers, and the TS mRNA level is closely correlated with immunohistochemical expression of TS (Johnston et al, 1995;Uchida et al, 2001). The pattern of immunohistochemical expression of p53 protein, the proportion of p53-positive cells, must be very important in discussing the relationship between p53 protein expression and gene mutation (Hall and Lane, 1994). The occurrence of occasional positive cells does not seem to correlate with obvious abnormality of p53 gene, but the positive staining in the majority of cells is frequently associated with gene mutation (Baas et al, 1994;Shiao et al, 2000).…”

Section: Evaluation Of Immunostainingmentioning

confidence: 99%

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Immunostaining of thymidylate synthase and p53 for predicting chemoresistance to S-1/cisplatin in gastric cancer

et al. 2007

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High expression of thymidylate synthase (TS) and inactivation of p53 are allegedly associated with chemoresistance. The authors evaluated TS and p53 expression in gastric cancer treated with neoadjuvant S-1/cisplatin chemotherapy. Paraffin sections of pretreatment biopsy and surgical specimens from 41 gastric cancers were immunostained for TS and p53 protein after appropriate antigen retrieval. Fifty-one cases without neoadjuvant chemotherapy were also studied. In the pretreatment biopsies, high expression of TS was seen in 8% of the histologic responders, in 28% of the nonresponders and in 31% of the controls. High expression of p53 was observed in 56% of the nonresponders, but in 8% of the responders and in 29% of the controls (Po0.01 and Po0.05, respectively). The TS-and/or p53-high phenotype was seen in 76% of the nonresponders and in 54% of the controls, but in 8% of the responders (Po0.0001 and Po0.005, respectively). The data of the surgical specimens were consistent with those of the pretreatment biopsies. These results suggest that immunostaining for TS and p53 protein is useful for pretreatment selection of gastric cancer patients unresponsive to S-1/cisplatin chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Evaluation Of Immunostainingmentioning

confidence: 99%

Immunostaining of thymidylate synthase and p53 for predicting chemoresistance to S-1/cisplatin in gastric cancer

et al. 2007

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“…Immunohistochemically demonstrated excess p53 protein may not necessarily reflect gene mutation (Hall and Lane, 1994). bcl-2 gene mutation may also lead to a functionally inactive protein product, which may still be detectable by immunohistochemistry.…”

Section: Cell Kinetics and Gene Expression In Lung Cancer 547mentioning

confidence: 97%

Cell proliferation, cell loss and expression of bcl-2 and p53 in human pulmonary neoplasms

Kennedy

Lamb²,

King³

et al. 1997

Br J Cancer

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Summary Immunohistochemical staining of bcl-2 and p53 proteins was compared with thymidine labelling index (TLI) and cell loss factor (0) in lung cancer. Neither bcl-2 nor p53 overexpression was associated with high cell loss but strong bcl-2 staining was associated with higher TLI. Concomitant strong p53 and bcl-2 expression, not the usual inverse relationship, plus high cell-loss factor was present in three neuroendocrine carcinomas. Other factors presumably have a role in controlling cell death in these tumours.Keywords: lung carcinoma; neuroendocrine; thymidine labelling index; cell loss factor; bcl-2; p53; apoptosis; immunohistochemistry Apoptosis is a major mechanism of tumour cell loss, itself a major determinant of tumour growth rate, and the protein products of both the p53 and bcl-2 genes have a role in this process. The functions of both these genes and their relationship to other regulatory proteins has been extensively reviewed (Lane, 1993;Piepentol and Vogelstein, 1993;Lu et al, 1996;Yang and Korsmeyer, 1996).In an earlier study (Kerr and Lamb, 1984), we derived data on cell proliferation and cell loss in 17 human lung tumours. Tumour thymidine labelling index (TLI) was measured in vitro and, using recognized methods and formulae (Collins et al, 1956; Steel 1967), a cell loss factor (0) was calculated. Cell loss factor expresses the proportion of cells being lost from a population relative to the number being added to it by mitotic activity. Thus a cell loss factor of 0.90 implies that for every 100 cells being added to a population by mitosis, 90 are lost by whatever means.In this study, we investigate the relationship between the cell proliferation/loss data in these 17 human lung tumours and their expression of the p53 and bcl-2 genes assessed immunohistochemically. MATERIALS AND METHODSThe histological classification of the tumours required revision of the original (Kerr and Lamb, 1984). 'Large-cell carcinoma with stratification' is now classified as poorly differentiated squamous carcinoma. One tumour, thought originally to be a metastatic deposit of large-cell carcinoma, now, with follow-up, fulfils criteria of a primary large-cell neuroendocrine cancer. Thirteen of the cases were typical bronchogenic carcinomas (six squamous, three adenocarcinoma, two small-cell undifferentiated, one largecell neuroendocrine and one large-cell undifferentiated carcinoma). Two were renal cell carcinoma metastases and one a primary clear cell carcinoma.Tumour thymidine labelling index (TLI) was obtained by in vitro incubation of tumour fragments with tritiated thymidine

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“…Immunohistochemistry is reasonably sensitive and easy to implement in diagnostic laboratories. However, truncated forms of p53 resulting from frameshift and nonsense mutations are not reliably detected by this approach (Hall and Lane, 1994;SjoÈ gren et al, 1996). Furthermore, wild-type p53 can be overexpressed without mutations (Moll et al, 1992;Cesarman et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

High frequency of p53 mutations in human oral epithelial dysplasia and primary squamous cell carcinoma detected by yeast functional assay

et al. 1997

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To determine the timing and actual incidence of p53 mutations in oral epithelial lesions, we examined 33 primary squamous cell carcinomas (SCCs), 14 dysplasias and six hyperplasias from Japanese patients by a combination of yeast functional assay and DNA sequencing. The assay detects mutations of p53 mRNA between codons 67 and 347 on the basis of the DNAbinding activity of the protein. Twenty-six SCCs (79%) and ®ve dysplasias (36%) were positive for p53 mutation, while all six hyperplasias were negative for the mutation. Human papillomavirus type 16 E6 mRNA was detected in one of seven p53 mutation-negative SCCs by reverse transcription polymerase chain reaction (RT ± PCR). We further examined p53 mutations in 17 Sri Lankan oral SCCs using the yeast functional assay and the singlestrand conformation polymorphism analysis of PCRampli®ed DNA fragments (PCR ± SSCP) of exon 5 ± 8. The mutations were con®rmed by DNA sequencing and the detection sensitivity was compared between the two methods. Six samples (35%) were positive for p53 mutation in PCR ± SSCP analysis, while nine samples (53%) were positive in yeast functional assay. This suggests that the incidence of p53 mutations has been considerably underestimated in the conventional SSCP analysis. The present data indicate that p53 mutations are extremely frequent in oral cancers in the Japanese, and suggest that the timing and signi®cance of p53 mutation in oral tumor progression vary in di erent ethnic populations and areas.

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p53 In tumour pathology: Can we trust immunohistochemistry?—revisited!

Cited by 548 publications

References 16 publications

Immunostaining of thymidylate synthase and p53 for predicting chemoresistance to S-1/cisplatin in gastric cancer

Immunostaining of thymidylate synthase and p53 for predicting chemoresistance to S-1/cisplatin in gastric cancer

Cell proliferation, cell loss and expression of bcl-2 and p53 in human pulmonary neoplasms

High frequency of p53 mutations in human oral epithelial dysplasia and primary squamous cell carcinoma detected by yeast functional assay

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