p53 and Bcl-2 as significant predictors of recurrence and survival in rectal cancer

Schwandner, O.; Schiedeck, Thomas; Bruch, Hans–Peter; Duchrow, M.; Windhoevel, U.; Broll, R.

doi:10.1016/s0959-8049(99)00271-3

Cited by 54 publications

(39 citation statements)

References 29 publications

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“…A study from the UK by Ilyas et al [31] demonstrated, similar to our study, that in patients with moderately differentiated Stage II CRCs (n = 66) with low Bcl-2 expression was associated with increased incidence of recurrence when adjusted for tumor stage and other clinicopathologic factors. Schwandner et al [32] from Germany also reported similar findings in rectal carcinomas (Stages I to III analyzed together). These results reinforce our current findings that decreased or lack of Bcl-2 expression is an important biomarker in the prediction of recurrence in Caucasians with Stage II CRCs.…”

Section: Discussionsupporting

confidence: 53%

“…The prognostic significance of Bcl-2 expression in CRCs has been reported in several studies [8,[27][28][29][30]; however, its value in predicting disease recurrence has not been studied extensively [30][31][32][33]. A study of Stage II CRCs from the US has demonstrated a positive association with increased expression of Bcl-2 and better relapse free survival; however, its role in predicting the recurrence of the disease has not been studied [30].…”

Section: Discussionmentioning

confidence: 99%

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Recurrence and survival predictive value of phenotypic expression of Bcl-2 varies with tumor stage of colorectal adenocarcinoma

Chatla

Jhala

Katkoori

et al. 2005

CBM

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Although decreased or lack of expression of Bcl-2 has been correlated with advanced tumor stage and shortened patient survival in colorectal cancer (CRC), its value in predicting the recurrence has not been well explored. Therefore, we assessed the usefulness of phenotypic expression of Bcl-2 in non-Hispanic Caucasian patients with CRCs in identifying risk of recurrence. Archival tissues of 92 Stage II and 66 Stage III primary CRCs were evaluated for immunohistochemical expression of Bcl-2. None of these patients received either pre-or post-surgical adjuvant therapies. Kaplan-Meier and Cox proportional hazards methods were used to estimate the rates of recurrence and survival according to Bcl-2 expression. Decreased expression of Bcl-2 was associated with an increased rate of recurrence in patients with Stage II CRCs (5-year log-rank test P = 0.0015; Hazard-Ratio (HR) = 3.90, 95%C.I.: 1.55-9.77) but not with Stage III CRCs (5-year log-rank test P =0.6058; HR =1.07, 95%C.I.: 0.47-2.45) after adjusting for other demographic and clinicopathological features. Furthermore, decreased expression of Bcl-2 was an indicator of short survival in patients with Stage II CRCs but not with Stage III CRCs. Thus, decreased or lack of Bcl-2 expression in primary CRCs may serve as a molecular biomarker of high risk of recurrence for Caucasian patients with Stage II CRCs. These findings might be useful in identifying biologically aggressive phenotypes of Stage II CRCs, and may aid the oncologist in designing maximally appropriate therapeutic regimens.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Recurrence and survival predictive value of phenotypic expression of Bcl-2 varies with tumor stage of colorectal adenocarcinoma

Chatla

Jhala

Katkoori

et al. 2005

CBM

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“…Technical differences can be expected for settings, antibodies, methods of antigenic retrieval, staining scores and interpretation criteria. Immunoreactivity can range from less than 10% to nearly 100%, depending on the tissue sample and interpretation criteria of the reaction (2,4,6,10,12,16,17,19,24,26) . In this study, 29.5 % of the cases were bcl-2 positive, similar to the results of other authors (6,10,24) , despite differences on the immunohistochemistry method.…”

Section: Discussionmentioning

confidence: 99%

“…Some authors (3) had demonstrated that bcl-2 overexpression seems to be associated with advanced histological grade, resulting in a more aggressive tumour. Others (2,4,9,14,24) had showed that patients with bcl-2 positive colorectal carcinoma had a more favourable clinical course. Finally, some studies (5,12,16,19,23) had failed to demonstrate any correlation between bcl-2 expression and well-known prognostic features, in agreement with our results.…”

Section: Discussionmentioning

confidence: 99%

Bcl-2 expression in rectal cancer

Contu

Moreira

2006

Arq. Gastroenterol.

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-Background -Proteins involved in apoptosis process seem to play an important role in colorectal carcinogenesis.Aim -To determine the prevalence of bcl-2 protein immunohistochemical expression and its relation with clinical and histopathological variables of rectal adenocarcinoma. Patients and methods -One hundred and thirty-two patients operated at "Hospital de Clínicas de Porto Alegre", Porto Alegre, RS, Brazil, between 1988 and 1999 were studied through immunohistochemical reaction using a monoclonal antibody anti-bcl-2 on formalin-fi xed, paraffi n-embedded tissue samples.Results -The prevalence of bcl-2 protein was 29.5%. There was a signifi cant increased number of positive bcl-2 cases among women as compared to men. There was no signifi cant association between bcl-2 and age, tumour site, histological grade, mucin production, depth of invasion, lymphatic involvement, distant metastasis or stage, despite a trend showing decreased immunoreactivity to bcl-2 among poorly and moderately differentiated tumours, as well as disseminated disease.Conclusions -Analysis of bcl-2 protein expression in tumour tissues, as well as other oncoproteins, may have a role in predict therapeutic response and prognosis of colorectal cancer. However, the potential use of bcl-2 protein assessment in the clinical set for management of rectal cancer remains to be determined.

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“…2,25,26 However, several large studies, including the present one, have failed to demonstrate that p53 confers any consistent and significant prognostic impact, which argues against a prognostic role for p53 immunostaining in rectal cancer. 12,27,28 p53 inhibits expression of the antiapoptotic Bcl-2 protein and mediates apoptosis via the Bcl-2/BAX pathway. A high degree of Bcl-2 expression has been demonstrated in distal colorectal cancers, and Bcl-2 has been implicated as a prognostic factor in colorectal cancer, with Bcl-2 expression signifying a favorable prognosis; especially poor prognosis has been observed for the subset of tumors with the molecular phenotype p53 ϩ /Bcl-2 -.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical patterns in rectal cancer: Application of tissue microarray with prognostic correlations

Fernebro

Bendahl²,

Dictor³

et al. 2004

Intl Journal of Cancer

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We utilized the high-throughput tissue microarray method to characterize immunohistochemical expression patterns with correlations to prognosis in rectal cancer. Immunostaining for the markers Ki-67, Bcl-2, p53, EGFR, Ecadherin, ␤-catenin, MLH1 and MSH2 was performed in 269 rectal cancers. Expression profiles were correlated to metastasis-free survival. Colorectal cancer is estimated to be the second leading cause of cancer death worldwide. 1 Differences in etiology, clinical behavior, pathologic features and genetic alterations apply to right-sided vs. left-sided colorectal tumors, which indicate that different mechanisms drive tumorigenesis at these sites. 2,3 Approximately 35% of colorectal cancers are located in the rectum, and rectal cancer affects males at a rate of 1.5:1 compared to females, with 75% of cases diagnosed after 65 years of age. Treatment advances such as the standardized surgical technique TME, preoperative radiotherapy and adjuvant chemotherapy have reduced the previously high local recurrence rate and improved survival in rectal cancer patients. Despite these advances, about 40% of patients still die from disseminated disease. 4 -6 Hence, there is a need for novel markers that allow improved identification of high-risk patients who would benefit from adjuvant treatment. 7 Colorectal cancer is one of the best-characterized tumor types at the molecular level. Numerous genetic alterations in oncogenes, tumor-suppressor genes and DNA MMR genes are acquired during tumorigenesis, which occurs through successive waves of clonal expansion according to 2 major mutational pathways, the CIN and MSI pathways. 8,9 Although the sequential accumulation of genetic changes that characterize the adenoma-carcinoma sequence of colorectal cancer applies also to rectal cancer, few studies have separately analyzed these tumor types. Rectal cancer has been associated with high proliferative activity, frequent aneuploidy and loss of heterozygosity at 17p and 18q, mutation/overexpression of p53 and consequently low frequencies of diploid tumors and MSI. 2,3,10 -12 Since the frequencies of the different genetic alterations vary according to tumor location within the bowel, studies investigating a possible prognostic role of biologic parameters should optimally analyze these tumor types separately.Several tumor-associated proteins may be relevant prognostic markers in rectal cancer. However, no single molecular marker has been demonstrated to provide consistent and independent prognostic information, and despite advances in our understanding of the pathogenesis of rectal cancer, molecular markers have not gained utility in clinical decision making. 7,13,14 The TMA technology allows high-throughput analysis of molecular markers and thereby facilitates studies of multiple markers in large tumor series. 15 Our aim was to apply TMA to investigate the expression patterns of multiple markers and their prognostic correlations in a large series of rectal cancer patients. These markers, which included Ki-67, p53, Bcl-2, EGF...

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p53 and Bcl-2 as significant predictors of recurrence and survival in rectal cancer

Cited by 54 publications

References 29 publications

Recurrence and survival predictive value of phenotypic expression of Bcl-2 varies with tumor stage of colorectal adenocarcinoma

Recurrence and survival predictive value of phenotypic expression of Bcl-2 varies with tumor stage of colorectal adenocarcinoma

Bcl-2 expression in rectal cancer

Immunohistochemical patterns in rectal cancer: Application of tissue microarray with prognostic correlations

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