The Significance of c-erb B-2 and p53 Immunoreactivity in Patients with Adenocarcinoma of the Esophagus

Duhaylongsod, Francis G.; Gottfried, Marcia R.; Iglehart, J. Dirk; Vaughn, Anna; Wolfe, Walter G.

doi:10.1097/00000658-199506000-00007

Cited by 83 publications

(51 citation statements)

References 20 publications

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“…Casson et al (20) reported a series of 61 patients in which p53 alterations (gene mutation and protein accumulation) occurred mainly in poorly differentiated adenocarcinoma which showed significantly reduced postoperative survival. However, Duhaylongsod et al (43) and Coggi et al (44) failed to find any association between p53 gene mutation or protein accumulation and survival in patients with esophageal adenocarcinoma. In this study, we found no correlation between p53 mutation or nuclear overexpression and clinicopathological parameters.…”

Section: Discussionmentioning

confidence: 97%

p53 Gene Mutation and Protein Accumulation during Neoplastic Progression in Barrett's Esophagus

et al. 2001

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The aim of the present study was to characterize expression and mutation of p53 during the neoplastic progression from Barrett's esophagus to adenocarcinoma and to test the reliability of immunohistochemistry for p53 overexpression as an indicator of p53 mutation in this context. The association of both gene mutation and protein accumulation with clinicopathological findings and survival was also studied. A total of 77 samples from 30 esophagectomy specimens with Barrett's esophagus and adenocarcinoma of patients in longitudinal clinical follow-up were analyzed. Different lesions (intestinal metaplasia, dysplasia, and adenocarcinoma) as well as normal squamous-cell esophageal epithelia were sampled from formalin-fixed, paraffinembedded tissues by microdissection. Mutations in p53 Exons 5 to 9 were detected by polymerase chain reaction-single-strand conformation polymorphisms (PCR-SSCP) and confirmed by direct DNA sequencing. Nuclear accumulation of p53 protein was analyzed immunohistochemically from tissue sections adjacent to those used for microdissection. p53 gene mutations were found in 17 and p53 protein accumulation were found in 20 tumor samples. Of the 17 adenocarcinomas with a p53 mutation, 16 stained positive for p53 protein. p53 mutations were detected significantly more frequently in high-grade dysplastic than in low-grade dysplastic lesions (77% versus 29%, P < 0.01). In contrast, nuclear accumulation of p53 was detected in 85% of high-grade and 71% of low-grade dysplastic lesions. In eight cases with p53 mutation, the mutation identified in the tumors was also detected in premalignant lesions, mainly in high-grade dysplasia. In four cases of p53-mutated tumors, clones with different p53 mutations were detected in premalignant lesions. Neither p53 mutations nor p53 protein accumulations were found in metaplastic lesions. In summary, we found that p53 mutations occurred mainly during the transition from low-grade to high-grade dysplasia in the neoplastic progression of Barrett's esophagus but not in the nondysplastic Barrett's mucosa. Mutational analysis of p53 by PCR-SSCP and p53 accumulation by immunohistochemistry were mostly concordant in adenocarcinoma and high-grade dysplastic lesions but frequently discordant in low-grade dysplastic lesions. No correlation between p53 gene mutation or p53 accumulation and clinicopathological findings was observed in this study.

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Section: Discussionmentioning

confidence: 97%

p53 Gene Mutation and Protein Accumulation during Neoplastic Progression in Barrett's Esophagus

et al. 2001

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“…This result is in line with the results of most previous studies. 28,31,32,36 The existence of several published papers reporting associations of HER-2 amplification/overexpression with both poor 24,35,42 and improved prognosis 25,30 also rather argue against an important prognostic role of HER-2 in esophageal cancers. The general absence of an association of HER-2 amplification or overexpression with clinical parameters of malignancy is in line with previous studies.…”

Section: Discussionmentioning

confidence: 99%

Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus

et al. 2007

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HER-2 is the target for antibody based treatment of breast cancer (Herceptin s ). In order to evaluate the potential role of such a treatment in esophageal cancers, HER-2 amplification and overexpression was investigated in primary and metastatic cancers of the esophagus. A tissue microarray was constructed from 255 primary esophageal cancers (110 adenocarcinomas and 145 squamous cell carcinomas), 89 nodal and 33 distant metastases. Slides were analyzed by immunohistochemistry (HercepTestt; DAKO) and fluorescence in situ hybridization (FISH; PathVysiont; Vysis-Abbott) for HER-2 amplification and overexpression. Amplification was seen in 16/110 (15%) adenocarcinomas and in 7/145 (5%) squamous cell carcinomas. There was a strong association between HER-2 amplification and overexpression, especially in adenocarcinomas (Po0.0001, log rank). There was a 100% concordance of the HER-2 results in primary tumor and corresponding metastases in 84 analyzed pairs. Amplification was typically high-level with more than 10-15 HER-2 copies per tumor cell. Amplification was unrelated to survival, grading, pT, pN, pM or UICC stage. We conclude that esophageal adenocarcinomas belong to those cancer types with relevant frequency high-level HER-2 gene amplification clinical trials or individual case studies investigating the response of metastatic HER-2-positive esophageal cancers to Herceptin s should be undertaken. The strong concordance of the HER-2 status in primary and metastatic cancers argues for a possible response of metastases from patients with HER-2-positive primary tumors to Herceptin s .

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“…Akamatsu et al [72] found HER-2 expression to be a predictor of chemoresistance in esophageal squamous cell carcinoma. In contrast, others have shown that HER-2 expression predicts a favorable response to chemo-or radiotherapy and thus improves survival [73]. The reasons for these contradictory results need to be addressed in future studies.…”

Section: The Role Of Her-2 In Esophageal Cancermentioning

confidence: 92%

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

et al. 2007

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Esophageal cancer is a highly aggressive disease and is the seventh most common cause of cancer-related death in the western world. Worldwide, it ranks as the sixth most frequent cause of cancer death. Despite advances in surgical techniques and treatment, the prognosis of esophageal cancer remains poor, with very few longterm survivors. The need for novel strategies to detect esophageal cancer earlier and to improve current therapy is urgent.It is well established that growth factors and growth factor receptor-mediated signaling pathways are important components of the transformation process in many forms of cancer, including esophageal cancer. With the recent advances in drug development, there are emerging possibilities to use growth factor signal transduction pathways in targeted therapy. This review provides a summary of the role of growth factors and their receptors in esophageal cancer and discusses their potential roles as biomarkers and as targets in therapy.

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The Significance of c-erb B-2 and p53 Immunoreactivity in Patients with Adenocarcinoma of the Esophagus

Abstract: Although p53 protein overexpression is commonly observed in adenocarcinoma of the esophagus, its prognostic value appears limited. In contrast, c-erb B2 protein expression predicts a favorable response to therapy and improved survival.

Cited by 83 publications

References 20 publications

p53 Gene Mutation and Protein Accumulation during Neoplastic Progression in Barrett's Esophagus

p53 Gene Mutation and Protein Accumulation during Neoplastic Progression in Barrett's Esophagus

Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus

Activation of Growth Factor Receptors in Esophageal Cancer—Implications for Therapy

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