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, Marshall

doi:10.1002/(sici)1097-0142(19980701)83:1<7::aid-cncr2>3.3.co;2-8

Cited by 32 publications

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“…18,19) With regard to esophageal cancers, the relationship of p53 status to prognosis also remains controversial. 8,9) Among the relatively large number of patients we examined, it appeared that those whose tumors carried p53 mutations tended to have poorer prognoses than the others. However, when we divided the patients with p53 mutations according to the intragenic locations of the alterations, the difference became more evident; tumors that contained p53 mutations within the L2 or L3 zinc-binding domains conferred statistically worse prognoses than the other tumors.…”

Section: Discussionmentioning

confidence: 98%

“…[5][6][7] However, the claim that p53 mutation can be a general prognostic indicator, or a predictor for response to therapy, remains controversial. 8,9) In the study reported here we examined the mutational status of p53 in esophageal cancers from 138 patients, and investigated the correlation of mutations with either the patients' prognoses or their response to chemotherapy or radiation. We determined that mutations in a specific region of the p53 gene may be predictive of both clinical outcome and response to these types of therapy for patients with esophageal cancers.…”

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confidence: 99%

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Mutations in Zinc‐binding Domains of p53 as a Prognostic Marker of Esophageal‐cancer Patients

Kihara

Seki

Furukawa

et al. 2000

Japanese Journal of Cancer Research

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Some investigators have suggested that mutations of the p53 gene may be molecular markers for poor prognosis of cancer patients, although others have reported conflicting results. We examined esophageal cancers from 138 patients to investigate whether mutational status of p53 could be correlated either with prognosis or with response to chemotherapy or radiation. We detected p53 mutations in the tumors of 78 (56.5%) patients. Kaplan-Meier analysis showed that these 78 patients tended to have shorter survival times and greater resistance to either form of therapy than patients whose tumors carried two wild-type p53 alleles. The difference became more evident when we focused on mutations in zinc-binding domains of p53 (L2 and L3); the prognosis was significantly poorer among the 29 patients with tumors in this category than among patients whose tumors had no p53 mutations, or p53 mutations outside L2 or L3 (P = = = =0.0060). Moreover, those tumors as a group were more resistant to chemotherapy or radiation than the others (P = = = =0.0105).Our results underscore the importance of the zinc-binding domains of p53 with respect to clinical prognosis for patients with esophageal carcinomas.

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Section: Discussionmentioning

confidence: 98%

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confidence: 99%

Mutations in Zinc‐binding Domains of p53 as a Prognostic Marker of Esophageal‐cancer Patients

Kihara

Seki

Furukawa

et al. 2000

Japanese Journal of Cancer Research

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“…As shown in Table 4, the reported frequencies of p53 gene mutation in esophageal cancer varied widely from 17 to 84%. (1)(2)(3)(4)(5)(6)(7)(8)10,11,(18)(19)(20)(21) There are several reasons for this variation. First, the variation may depend on the sensitivity of the mutation detection system.…”

Section: Discussionmentioning

confidence: 99%

p53 Gene mutations in esophageal squamous cell carcinoma and their relevance to etiology and pathogenesis: Results in Japan and comparisons with other countries

et al. 2007

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Esophageal squamous cell carcinoma is a form of cancer that has varying incidence rates among different countries, distinct geographic areas and different ethnic groups. According to previous reports, p53 gene mutations have been identified in 20-80% of these tumors, and these mutations have occurred at an early stage. These findings suggest that such mutations play an important role in esophageal carcinogenesis, and highlight the importance of mutagens, which cause sequence alterations in the p53 gene. In order to clarify the environmental factors and the molecular mechanisms that may be responsible for the occurrence and prevention of a specific mutation in the process of esophageal carcinogenesis, we analyzed p53 gene mutations in 95 samples of esophageal squamous cell carcinoma. We further reviewed published reports investigating the frequency of p53 gene mutations in esophageal cancer from high-risk areas to normal-risk areas and compared these findings to our results in Japan E sophageal cancer is the sixth most common cause of cancer death in the world. There are two major histological types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. Although the incidence of the latter type has been increasing, especially in the USA and Europe, the former histological type is predominant worldwide, including in Japan. There is a marked geographic and ethnic variation in the incidence of this cancer. The high-risk regions are North Central China, (1)(2)(3) Northern Iran, (4,5) Normandy in France (6,7) and some areas in South Africa.(8) The different etiological factors, such as thermal irritation, dietary factors, and nutritional deficiencies in antioxidants, could therefore play a role in carcinogenesis. Alcohol consumption and tobacco smoking have been shown to be major risk factors for esophageal cancer in most Western countries. The development and progression of esophageal cancer are multistep processes that require the accumulation of specific alterations in the genes regulating cell growth, differentiation, apoptosis, and so on. Among them, the wild-type p53 protein plays a crucial role in cell proliferation by arresting the cell cycle in G 1 phase, regulating apoptosis and suppressing angiogenesis. Mutations in the p53 gene have been reported in over half of all human cancers and they appear to occur at an early stage of esophageal cancer, thus indicating the important role of such mutations in esophageal carcinogenesis. Alcohol and tobacco are well-known factors contributing to the induction of p53 gene mutation in ESCC. Moreover, dietary carcinogens or habits have also been reported to be causal factors inducing p53 mutations in ESCC in some high-risk areas such as China, Southern Brazil and Taiwan. (3,10 -12) Ionizing irradiation, ultraviolet exposure and chemical mutagens are all known to cause various kinds of DNA damage. In addition to those exogenous factors, endogenous factors such as oxygen radicals, deamination and the loss of bases can also cause DNA damage. Under normal condit...

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“…Two possibilities were suggested based on these data: It is possible that cyclin B1 affects disease progression and prognosis directly and that p53 regulates disease progression indirectly , because the expression of cyclin B1 and cdc2 activated cdc2 kinase constitutively, with the cells passing through G2‐M regardless of p53 expression. 11 Another possibility is that mutation of the p53 gene is more critical than elevated levels of immunohistochemical expression, because they are not related directly to each other 2, 4, 5. Because p53 ‐mutated or p53 ‐deficient cells do not undergo G2‐M arrest, further analysis of the p53 mutation status will be required 7, 8…”

Section: Discussionmentioning

confidence: 99%

“…However, despite investigation, the role played by p53 in the pathogenesis and progression of esophageal carcinoma remains unclear. 2–6 p53 regulates the G2‐M transition, a critical cell cycle checkpoint, and p53 ‐deficient or p53 ‐mutant cells undergo cell cycle arrest in the G2 phase 7, 8. Wild type p53 regulates Gadd45 protein, which inhibits the activity of the cdc2/cyclin B1 complex.…”

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Prognostic value of cyclin B1 in patients with esophageal squamous cell carcinoma

Takeno

Noguchi

Kikuchi

et al. 2002

Cancer

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BACKGROUND It has been reported that p53 regulates the G2‐M checkpoint transition through cyclin B1, and it has been suggested that p53 plays an important role in the development and progression of various malignancies. The objective of the current study was to clarify the role of the cell cycle regulators, cyclin B1 and p53, in patients with esophageal squamous cell carcinoma (ESCC). METHODS Tissue samples from 71 patients with ESCC were included in the current study. Expression levels of cyclin B1 and p53 in samples of normal squamous epithelium, dysplasia, and tumor cells from patients with ESCC were analyzed by immunohistochemistry. RESULTS Several cells in the basement layer of normal epithelium expressed cyclin B1. The number of cyclin B1 positive cells tended to increase as the degree of dysplasia increased from low grade to high grade. More than 20% of tumor cells were cyclin B1 positive in 38 patients (49.3%). Several clinicopathologic parameters, including macroscopic configuration (P < 0.01), pathologic tumor status (P < 0.05), pathologic lymph node status (P < 0.001), pathologic metastatic status (P < 0.01), tumor stage (P < 0.0001), and invasion of lymphatic vessels (P < 0.05), were correlated with the overexpression of cyclin B1. Elevated expression levels of cyclin B1 also were correlated with a poor prognosis in patients with ESCC in univariate analysis (P < 0.0001) and multivariate analysis (P = 0.0135). In contrast, p53 expression exhibited no significant correlation with the level of cyclin B1 expression and was not associated with prognostic parameters in patients with ESCC. CONCLUSIONS These findings suggest that cyclin B1 is involved in the pathogenesis of carcinoma of the esophagus and that elevated levels of cyclin B1 expression, but not p53 expression, may indicate a poor prognosis for patients with ESCC. Cancer 2002;94:2874–81. © 2002 American Cancer Society. DOI 10.1002/cncr.10542

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

Cited by 32 publications

References 0 publications

Mutations in Zinc‐binding Domains of p53 as a Prognostic Marker of Esophageal‐cancer Patients

Mutations in Zinc‐binding Domains of p53 as a Prognostic Marker of Esophageal‐cancer Patients

p53 Gene mutations in esophageal squamous cell carcinoma and their relevance to etiology and pathogenesis: Results in Japan and comparisons with other countries

Prognostic value of cyclin B1 in patients with esophageal squamous cell carcinoma

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