Expression of Bcl-2 protein is decreased in colorectal adenocarcinomas with microsatellite instability

Biden, Kelli G.; Simms, Lisa A.; Cummings, Margaret C.; Buttenshaw, Ron; Schoch, Estelle; Searle, Jeffrey; Gobé, Glenda C.; Jass, Jeremy R.; Meltzer, Stephen J.; Leggett, Barbara A.; Young, Joanne

doi:10.1038/sj.onc.1202413

Cited by 42 publications

(40 citation statements)

References 28 publications

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“…Our results also demonstrated the distinct correlations of p53 and Bcl-2 with tumor stage and grade (12,(17)(18)(19)(23)(24)(25). Bcl-2(+) lesions showed a trend for earlier stage and better grade, a finding supporting the connection of this marker with early tumorigenic steps (7,12,17,19) and also with a favorable prognostic impact (8,12,13,19).…”

Section: Discussionsupporting

confidence: 64%

“…One possible reason for this -apart from methodological factors (15,16) and the heterogeneity of CRC (11) -could be that the association between these markers and the conventional prognostic parameters remains unclear. p53 has been correlated with higher stage and poor grade (11,12,17,18); conversely, Bcl-2 has been linked to lower stage and better grade (12,17,19). Notwithstanding, these trends are generally inconsistent, as indicated by reviewing studies (6,10,14).…”

Section: Introductionmentioning

confidence: 95%

“…p53 expression was additionally scored as negative (<5%), low (5-30%), moderate (31-60%) and high (>60%). This classification was based on previous studies reporting prognostic, clinicopathological and molecular correlations of p53 using these thresholds (7,13,14,(17)(18)(19)(20). A similar categorization for Bcl-2 was deemed inappropriate because of the relatively lower proportion of positive staining (see Results).…”

Section: Study Populationmentioning

confidence: 99%

“…A similar categorization for Bcl-2 was deemed inappropriate because of the relatively lower proportion of positive staining (see Results). However, the chosen threshold (5%) was also found to reveal clinicopathological and molecular associations of this marker (17,19,21), whereas the previous use of multiple stratification did not provide any additional information (17,19). Staining intensity, considered as a less objective criterion, was not scored.…”

Section: Study Populationmentioning

confidence: 99%

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Disparate clinicopathological correlations of p53 and Bcl-2 in colorectal cancer

et al. 2011

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Abstract. p53 and Bcl-2 (both regulators of cell apoptosis) have been considered to be involved in the initiation and progression of the colorectal tumorigenic process, respectively. In this study, we investigated their association with tumor stage and grade -both substantially affecting prognosis. Immunohistochemical assessment of p53 and Bcl-2 was retrospectively conducted (using DO-7 and Ca-124 monoclonal antibodies, respectively) in 119 surgically resected colorectal carcinomas, and the results were correlated to tumor stage and grade. The proportion of tumors positively stained was 70% for p53 and 46% for Bcl-2, whereas co-expression of both markers was observed in 28% of cases. Tumors exhibiting the highest p53 staining (>60% stained cells) were more frequently found in disease stage IV (p=0.03), while Bcl-2 positivity showed a predilection for earlier stage (p=0.02) and better grade (p=0.028). The associations of both markers with stage, along with a reciprocal relationship between p53(+) and Bcl-2(+) tumors (p=0.02), stronger for cases with p53 staining >30% (p=0.007), remained significant only for distal tumors. The distinct correlations of p53 and Bcl-2 with disease progression and aggressiveness (being influenced by the extent of staining and tumor site) may be clinically useful in the determination of high-risk colorectal cancer cases.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 95%

Section: Study Populationmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

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Disparate clinicopathological correlations of p53 and Bcl-2 in colorectal cancer

et al. 2011

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“…This anti-proliferative property has been used to explain the putative tumour-suppressor activity of Bcl-2, which has been observed in transgenic mouse models of the mammary gland [13,14] and hepatic carcinogenesis [15,16]. In addition, elevated Bcl-2 levels have been associated with both a reduced proliferation rate and favourable prognosis in several human carcinomas, and a selective down-regulation of Bcl-2 has been observed during tumour progression in various human cancers [17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Bcl-2 activates a programme of premature senescence in human carcinoma cells

Crescenzi

Palumbo

Brady

2003

Biochemical Journal

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The apoptosis regulator Bcl-2 has been shown to modulate cellcycle progression, favouring a quiescent state over a proliferative state, in both normal and tumour cells. We show here that constitutive expression of Bcl-2 in human carcinoma cells results in a cell-cycle arrest that within a few days can become irreversible. Arrested cells acquire a senescent-like phenotype, which consists of several characteristic morphological alterations and increased activity of senescence-associated β-galactosidase. The induction of the premature senescence programme is mediated by inhibition of Cdk2 kinase activity, and p27 KIP1 is required to maintain the senescent phenotype. We propose that the ability to activate an endogenous premature senescence programme allows Bcl-2 to suppress tumour growth. These results suggest that the downregulation of Bcl-2 expression, which has been observed during the development and progression of human carcinoma, is related to the ability of Bcl-2 to severely hamper the growth of carcinoma cells and to induce a permanent cell-cycle arrest, with the features of senescence.

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