p53 sequence analysis predicts treatment response and outcome of patients with esophageal carcinoma

Ribeiro, Ulysses; Finkelstein, Sydney; Safatle‐Ribeiro, Adriana Vaz; Landreneau, Rodney J.; Clarke, Martha; Bakker, Anke; Swalsky, Patricia A.; Gooding, William E.; Posner, Mitchell C.

doi:10.1002/(sici)1097-0142(19980701)83:1<7::aid-cncr2>3.0.co;2-r

Cited by 120 publications

(67 citation statements)

References 56 publications

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“…VEGF expression was also identified as an independent prognostic factor. In contrast to previous reports (Ribeiro et al, 1998;Yang et al, 1999), we found that p53 expression was not a predictive indicator The patients having neoadjuvant CRT followed by surgery (n=31). The P-values were determined using log-rank test.…”

Section: Discussioncontrasting

confidence: 99%

“…p53, TP and VEGF protein over-expression in the biopsy specimens was detected by antip53 monoclonal antibody (DO-7, DAKO, Carpenteria, CA, USA), anti-human TP (Nippon Roche Research Center, Kamakura, Japan; Nishida et al, 1996) and anti-human VEGF (A-20, Santa Cruz Biotechnology, Inc., Santa Cruz, CA, USA) using conventional peroxidase methods (Ribeiro et al, 1998). In brief, 4 mm thick sections were deparaffinized in xylene, dehydrated through graded alcohol concentrations and incubated in citrate buffer (pH=6.0) for 5 min using a household microwave oven at 800 W. After microwave exposure, the slides were allowed to cool to room temperature.…”

Section: Molecular and Cellular Pathologymentioning

confidence: 99%

“…Indeed, genetic alteration of p53 or p53 protein over-expression has already been reported to be a good predictor for treatment response and survival in oesophageal cancer (Sarbia et al, 1994;Nabeya et al, 1995;Casson et al, 1998;Ribeiro et al, 1998;Yang et al, 1999;Kobayashi et al, 1999;Shimada et al, 2000).…”

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confidence: 99%

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Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma

et al. 2002

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The ability to predict patients' responses to chemoradiotherapy by analyzing pre-treatment biopsy specimens would be valuable for managing oesophageal squamous-cell cancer. To this end, the expression of p53, thymidine phosphorylase and vascular endothelial cell growth factor was analyzed by immunohistochemistry in 52 patients with oesophageal squamous-cell cancer prior to chemoradiotherapy. Treatment consisted of radiotherapy (40 Gy) and 5 day-infusion of 5-Fluorouracil (500 mg m 72 per day) combined with cisplatin (10 mg m 72 per day). Following treatment, imaging and endoscopic reassessment was performed to establish treatment response. Thirty-one patients underwent radical surgery and 21 patients were treated with an additional 20 Gy of radiotherapy. Of the tumours studied, 58% were p53-positive, 40% thymidine phosphorylase-positive and 44% vascular endothelial cell growth factor-positive. A clinical response was observed in 36 patients (69%) and was negatively associated with thymidine phosphorylase expression (P=0.02) and vascular endothelial cell growth factor expression (P50.001). However, the 5-year survival rate was significantly lower only in patients with vascular endothelial cell growth factor-positive tumours (P=0.037). Multivariate analysis identified vascular endothelial cell growth factor as a significant independent prognostic factor (P=0.0147). These results suggest that expression of angiogenic factors has predictive value for the treatment response and outcome of patients with oesophageal cancer.

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Section: Discussioncontrasting

confidence: 99%

Section: Molecular and Cellular Pathologymentioning

confidence: 99%

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Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma

et al. 2002

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“…However, the results have been equivocal. Thus, whereas some studies have indicated that p53 gene mutation and/or p53 protein accumulation in tumour cells may be significantly associated with resistance to multimodal therapy and/or poor survival (Seitz et al, 1995;Ribeiro et al, 1998;Sarbia et al, 1998;Krasna et al, 1999;Gibson et al, 2003), others have not found such a correlation (Soontrapornchai et al, 1999;Ito et al, 2001;Shimada et al, 2002;Pühringer-Oppermann et al, 2006). With regard to EGFR, two studies indicated that tumours with strong EGFR expression show a relatively poor response to chemoradiotherapy (Hickey et al, 1994;Gibson et al, 2003), whereas another study did not find such a correlation (Miyazono et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

The predictive value of molecular markers (p53, EGFR, ATM, CHK2) in multimodally treated squamous cell carcinoma of the oesophagus

et al. 2007

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Pretherapeutic identification of oesophageal squamous cell carcinomas that will respond to neoadjuvant chemoradiotherapy is an important attempt for improvement of patient's prognosis. In the current study, pretherapeutic biopsies from 94 oesophageal squamous cell carcinomas (cT3, cN0/ þ , cM0) in patients who underwent neoadjuvant chemoradiotherapy (RCTx: 45 Gy plus cisplatin and 5-fluorouracil) and subsequent oesophagectomy in the setting of a single-centre prospective treatment trial were investigated by means of immunohistochemistry. Expression of proteins involved in DNA repair and/or cell-cycle regulation, that is p53, p53 (phosphorylated at Ser15), EGFR, ATM protein kinase (phosphorylated at Ser1981) and checkpoint kinase 2 (CHK2) (phosphorylated at Thr68) was correlated with the response to RCTx and with overall survival. Tumours that were positive for CHK2 expression more frequently showed clinically determined regression after RCTx (69.4%) than tumours that were negative for CHK2 expression (32.1%; P ¼ 0.0011), whereas other parameters did not correlate with tumour regression. Expression of ATM correlated with expression of CHK2 (P ¼ 0.0061) and p53-phospho (P ¼ 0.0064). Expression of p53 correlated with expression of p53-phospho (Po0.0001). In contrast to clinical and histopathological response evaluation, none of the molecular parameters under investigation correlated with overall survival. In conclusion, expression analysis of p53, EGFR CHK2 and ATM has no predictive value in multimodally treated oesophageal squamous cell carcinoma.

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“…A detecção de mutação do p53 e a perda de alelo representam marcadores de prognóstico desfavorável (10,12,14) , todavia a utilidade da imunoistoquímica ainda é duvidosa e apresenta resultados conflitantes (2,9,11,13) . Apesar disso, geralmente ocorre forte associação entre imunoexpressão do p53 e análise gênica nos tumores retais, havendo falhas ao redor de 10% a 20% dos casos (18) .…”

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p53 na prática clínica: sim ou não?

Ribeiro

Safatle‐Ribeiro

2006

Arq. Gastroenterol.

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p53 sequence analysis predicts treatment response and outcome of patients with esophageal carcinoma

Cited by 120 publications

References 56 publications

Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma

Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma

The predictive value of molecular markers (p53, EGFR, ATM, CHK2) in multimodally treated squamous cell carcinoma of the oesophagus

p53 na prática clínica: sim ou não?

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