An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms

Baas, Inge O.; Mulder, Jan-Willem R.; Offerhaus, G. Johan A.; Vogelstein, Bert; Hamilton, Stanley R.

doi:10.1002/path.1711720104

Cited by 474 publications

(309 citation statements)

References 27 publications

Supporting

Mentioning

276

Contrasting

Unclassified

Order By: Relevance

“…Home et al (1996) recently concluded from a panel of MAbs used on breast cancers that pAbi 801 and DO-7 are among the most effective antibodies for IHC in routinely processed material. A similar study on colon cancers revealed that staining with DO-7 after an antigen retrieval method for paraffin sections was the most sensitive and specific procedure (Baas et al, 1994). It is therefore remarkable that Manne et al (1997), who used BP53-12-1 MAb after having established that it gave similar results as pAbI801, reported that the above antigen retrieval procedure abolished the relationship found between p53 positivity and patient survival.…”

Section: Bcl-2 Expressionmentioning

confidence: 94%

“…Tumours were assigned to one of three categories: high expression, more than 30% of cancer cells stained; low expression, 1-30% of cancer cells stained; and no expression, 0% cancer cells stained (Baas et al, 1994). Apart from nuclear staining, we also estimated the presence of cytoplasmic staining; staining intensity (SI) was scored as low, intermediate or high.…”

Section: Materials and Methods Patientsmentioning

confidence: 99%

“…In the present study we evaluated IHC of both p53 and Bcl-2 in a series of 238 paraffin-embedded colorectal carcinomas from patients that had a median follow-up of 40 months. We used the monoclonal antibody (MAb) D07 and the polyclonal antiserum CM-1 (Midgley et al, 1992) for p53 and the MAb Bcl-2:124 (Pezzella et al, 1990) for Bcl-2, analysing staining results as previously reported (Baas et al, 1994;Van Slooten et al, 1996). Our data clearly demonstrate that IHC with these antibodies does not provide information relevant to the prognosis of this series of colorectal cancer patients.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance

Tollenaar

Krieken²,

Slooten³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

Summary To evaluate the prognostic significance of immunohistochemically detected p53 and Bcl-2 proteins in colorectal cancer, tissue sections from 238 paraffin-embedded colorectal carcinomas were immunostained for p53 (MAb DO-7 and CM-1 antiserum) and Bcl-2 (MAb Bcl-2:124). Staining patterns were assessed semiquantitatively and correlated with each other and with sex, age, tumour site, Dukes' classification, tumour differentiation, mucinous characteristics, lymphocyte and eosinophilic granulocyte infiltration, and patient survival. In our series, 35% of carcinomas showed no nuclear staining and 34% (DO-7) to 40% (CM-1) showed staining in over 30% of tumour cell nuclei. A majority of carcinomas that had been immunostained with CM-1 showed cytoplasmic staining, but this was not observed with DO-7. With respect to Bcl-2, 51% of tumours were completely negative, 32% displayed weak and 15% moderate staining; only 3% showed strong positive staining. No evidence was found for reciprocity between Bcl-2 expression and nuclear p53 accumulation. From 13 cases containing tumour-associated adenoma, four were Bcl-2 negative in premalignant and malignant cells, in another four cases these cells showed similar staining intensities and in the remaining cases only the malignant colorectal cells were Bcl-2 negative. Therefore, our data indicate that Bcl-2 is dispensable in the progression towards carcinoma. Except for an association between nuclear p53 accumulation and mucinous tumours (P = 0.01), no significant correlation was found between the clinicopathological parameters mentioned above and immunostaining pattern of (nuclear or cytoplasmic) p53 or Bcl-2.Keywords: colorectal neoplasm; p53; Bcl-2; immunohistochemistry; prognosis At present, prognostication for colorectal cancer is based mainly on tumour stage, but, because marked differences in clinical outcome occur within each stage, there is an obvious need for better prognostic markers. Ideally, these markers should predict the chance that the tumour has disseminated at the time of primary surgery, thereby facilitating selection of subgroups of patients who might benefit from adjuvant chemotherapy and radiation therapy. For this purpose we selected a population of patients who underwent a curative resection without adjuvant chemotherapy and for whom post-operative follow-up was available.In normal colorectal mucosa there exists a stringently controlled balance between cell proliferation and cell death, and it has been hypothesized that a reduced capacity to undergo apoptotic cell death could be an important step in the development of neoplasia. (Bedi et al, 1995). Both the product of the tumour suppressor gene p53 and the products of the bcl-2 gene family are involved in regulation of cell proliferation and apoptosis, and alterations in these genes are related to oncogenesis and disease progression.Loss of p53 function has been strongly linked to development of malignancy (Hollstein et al, 1991) -about 70% of colorectal cancers were shown to bear p53 mutations and a simila...

show abstract

Section: Bcl-2 Expressionmentioning

confidence: 94%

Section: Materials and Methods Patientsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance

Tollenaar

Krieken²,

Slooten³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Non-neoplastic colorectal mucosa, lymphocytes and stromal cells did not show any immunoreactivity. Although detection of p53 overexpression by immunocytochemical means does not necessarily imply a mutant form of the gene, in most (85%) of the cases p53 overexpression coincides with an underlying mutation (Bass et al, 1994).…”

Section: P53 Immunostainingmentioning

confidence: 96%

Bcl-2 protein expression: association with p53 and prognosis in colorectal cancer

Kaklamanis

Savage²,

Whitehouse³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

Summary Bcl-2 expression in colorectal carcinomas was studied in a series of 224 patients and the relation to p53 expression, stage and survival assessed. Bcl-2 expression was down-regulated compared with normal mucosa in 67% (151) of the cases. In 144 cases staining was positive for p53 (MAB D07), and 41 of these 144 p53-positive cases were also bcl-2 positive (28%) comeared with 32 of the remaining 80 p53-negative cases (40%). Survival was significantly worse (P = 0.01) in the p53-positive cases. Bcl-2-positive cases, including patients in all Dukes' stages, had a slightly better prognosis which was not statistically significant. However, cases at an early stage (Dukes' stages A and B) and with negative p53 status, had a much better prognosis if they showed bcl-2 protein expression, suggesting that the bcl-2 status itself has an effect on prognosis (P= 0.01). Neither bcl-2 nor p53 alone was correlated with stage, but when examined by both p53 and bcl-2 status a group [bcl-2(+)/p53(-)] with better prognosis was defined. The last group was significantly lower Dukes' stage, with 26 out of 32 cases (81 %) being A or B compared with 22 (11 %) of the 202 remaining cases (P = 0.004). Thus, either loss of bcl-2 expression or gain of abnormal p53 expression is associated with high stage and poor prognosis. The bcl-2(+)/p53(-) phenotype is similar to that of normal mucosa, and these results suggest that such cases represent an indolent group at an early stage in the progression of colorectal cancer.

show abstract

“…5 Immunohistochemistry for microsatellite analysis of markers hMLH1 and hMSH2 was carried out according to the method of Alexander et al 18 Immunohistochemistry for p53 protein was also performed according to previously published method. 19 Overexpression of p53 protein was considered to be present when more than 50% of the nuclei of tumor cells were strongly stained.…”

Section: Molecules Analysesmentioning

confidence: 99%

Genetic analysis of sinonasal adenocarcinoma phenotypes: distinct alterations of histogenetic significance

et al. 2005

View full text Add to dashboard Cite

Sinonasal adenocarcinomas, a relatively rare entity, are composed of distinctly different morphologic subtypes with variable biological behavior. To investigate the genetic events associated with their development and clinicopathologic features, we analyzed the alterations in K-ras, APC, b-catenin, hMLH1 and hMSH2 and p53 genes expression in a cohort of 15 primary tumors comprising the two main sinonasal adenocarcinoma subtypes (enteric and seromucinous). The patients consisted of 13 men and two women, who ranged in age from 50 to 87 years. Tumors were predominantly located in the ethmoid sinus. Eight tumors were Enteric-type, and seven were seromucinous type. Nine patients were smokers and four were nonsmokers; and no information was available on two patients. Two of the eight enteric-type, had K-ras mutation at codons 12A and 12B, and one showed microsatellite instability at BAT-25. Two patients with enteric-type tumors had a history of wood-dust exposure, and one had a K-ras mutation at 12A codon as well as p53 overexpression. No patients with the seromucinous type had any genetic abnormalities, except for overexpression of p53 in two tumors. Our results show that (1) a subset of enteric-type sinonasal adenocarcinoma shares certain genetic alterations with colonic adenocarcinomas, (2) the seromucinous-type sinonasal adenocarcinoma lacks alterations and may develop through a different pathway, (3) high p53 expression is associated with aggressive tumor features in both subtypes and (4) the enteric-type runs a more malignant course than the seromucinous counterpart.

show abstract

An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms

Cited by 474 publications

References 27 publications

Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance

Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance

Bcl-2 protein expression: association with p53 and prognosis in colorectal cancer

Genetic analysis of sinonasal adenocarcinoma phenotypes: distinct alterations of histogenetic significance

Contact Info

Product

Resources

About