Apoptosis and immunohistochemicalbcl-2 expression in colorectal adenomas and carcinomas: Aspects of carcinogenesis and prognostic significance

Baretton, Gustavo; Diebold, Joachim; Christoforis, Gregor; Vogt, Michael; Müller, Christian; Dopfer, Karin; Schneiderbanger, Karin; Schmidt, Michael; Löhrs, U.

doi:10.1002/(sici)1097-0142(19960115)77:2<255::aid-cncr6>3.0.co;2-l

Cited by 216 publications

(181 citation statements)

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“…Among the different approaches to evaluate cell susceptibility to the activation of apoptosis, we focused on the expression of two negative and positive regulatory proteins, bcl-2 and bax, whose immunocytochemical determination proved to be feasible on archival specimens and associated with tumour progression and treatment response in different clinical situations involving various tumour types (Krajewski et al, 1995;Barretton et al, 1996;Apolinario et al, 1997;Bonetti et al, 1998;Silvestrini et al, 1998;Tai et al, 1998;Daidone et al, 1999;Ogura et al, 1999;Sturm et al, 1999). Bax represents a pro-apoptotic member of the bcl-2 family which controls important checkpoints during the apoptotic process and whose transcriptional activation is induced by wild-type p53.…”

Section: Discussionmentioning

confidence: 99%

Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer

Paradiso¹,

Simone²,

Lena³

et al. 2001

Br J Cancer

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SummaryThe clinical relevance of bax and bcl-2 protein expression has been investigated in 84 patients with recurrent or metastatic colorectal cancer submitted to a chemotherapy regimen including methotrexate and fluorouracil/leucovorin. Cytoplasmic immunostaining of bax and bcl-2 was present in 65.5% and 38%, respectively, of the tumours. No association was found between bax and bcl-2 or between p53 and bax or bcl-2 protein expression. Moreover, the biomarkers were unrelated to patient and tumour characteristics known to affect the clinical outcome of colorectal cancer patients. In general, the apoptosis-related markers did not appear indicative of short-and long-term clinical response nor of prognosis. Bcl-2-negative lesions were more frequent among patients who reached an objective clinical response, which is in agreement with previously reported data regarding other tumour types. When the interrelationship between p53 and bax expression was examined, a better response rate (40%) was found for patients whose tumours did not express p53 and bax, and a better prognosis (2-year probability of overall survival 75%) for patients with p53-positive and bax-negative tumours. In the present series of patients with advanced colorectal cancer submitted to systemic chemotherapy we did not find a clear association between expression of apoptosis-related markers and clinical outcome, even in the subset of patients in which the apoptotic index as determined by the TUNEL approach was investigated.

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Section: Discussionmentioning

confidence: 99%

Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer

Paradiso¹,

Simone²,

Lena³

et al. 2001

Br J Cancer

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“…British Joural of Cancer (1998) 77(11), [1842][1843][1844][1845][1846][1847] TNM as stratification factor (Offner et al, 1995;Manne et al, 1997), but others could not confirm this independence (Baretton et al, 1996) and neither we nor Bosari et al (1993) could find any correlation with a better clinical course. Moreover, using a MAb different from that used in the above studies, Schneider et al (1997) concluded Bcl-2 expression not to be associated with survival or response to 5-fluorouracil-based chemotherapy.…”

Section: Bcl-2 Expressionmentioning

confidence: 91%

“…Reported correlations include tumour differentiation (Watson et al, 1996;Schneider et al, 1997), lymphocyte infiltration and tumour size (Ofner et al, 1995), and factors such as bowel wall and regional lymph node invasion and presence of distant metastases (Manne et al, 1997). It was also reported that Bcl-2-negative tumours tend to have higher apoptotic indices (Baretton et al, 1996). But, as with p53, the literature is far from equivocal on this subject.…”

Section: Bcl-2 Expressionmentioning

confidence: 99%

“…(Bosari et al, 1995;Baretton et al, 1996;Flohil et al, 1996;Watson et al, 1996;Ward et al, 1997). With respect to the prognostic significance of Bcl-2 staining in colorectal carcinomas, data were not conclusive (Bosari et al, 1995;Ofner et al, 1995;Baretton et al, 1996). Moreover, whereas in adenomas an inverse relationship was found between Bcl-2 expression and p53 accumulation, this could not be confirmed in carcinomas (Sinicrope et al, 1995;Baretton et al, 1996).…”

mentioning

confidence: 99%

“…With respect to the prognostic significance of Bcl-2 staining in colorectal carcinomas, data were not conclusive (Bosari et al, 1995;Ofner et al, 1995;Baretton et al, 1996). Moreover, whereas in adenomas an inverse relationship was found between Bcl-2 expression and p53 accumulation, this could not be confirmed in carcinomas (Sinicrope et al, 1995;Baretton et al, 1996). However, a dual staining technique for both Bcl-2 and p53 suggested reciprocity of expression within individual tumours (Watson et al, 1996).…”

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confidence: 99%

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

Tollenaar

Krieken²,

Slooten³

et al. 1998

Br J Cancer

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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...

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Apoptosis in colorectal carcinoma occurring in patients aged 45 years and under: relationship to prognosis, mitosis, and immunohistochemical demonstration of p53, c-myc and bcl-2 protein products

et al. 1997

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Apoptosis and immunohistochemicalbcl-2 expression in colorectal adenomas and carcinomas: Aspects of carcinogenesis and prognostic significance

Cited by 216 publications

References 40 publications

Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer

Expression of apoptosis-related markers and clinical outcome in patients with advanced colorectal cancer

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

Apoptosis in colorectal carcinoma occurring in patients aged 45 years and under: relationship to prognosis, mitosis, and immunohistochemical demonstration of p53, c-myc and bcl-2 protein products

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