Abstract
OBJECTIVE: Studies in breast cancer suggest that p53 and c-erb B2 protein overexpression are predictive of outcome. The authors determined whether these molecular markers correlated with treatment response and survival in patients with adenocarcinoma of the esophagus and esophagogastric junction. METHOD: Immunostaining for p53 and c-erb B2 was performed on paraffin-embedded specimens from 42 patients with esophageal adenocarcinoma. All patients received neoadjuvant chemotherapy (cisplatin and fluorouracil [5-FU] x 3 cycles) and irradiation (4500 rads) followed by resection. RESULTS: In this cohort of patients, 79% (33/42) were positive for p53, and 43% (18/42) were positive for c-erb B2. p53 positivity correlated with residual disease in the resection specimen but not with disease-free survival. Although c-erb B2 negatively correlated with residual disease after resection and a 5-year survival of 10%, c-erb B2 positivity was associated with a 5-year actuarial survival of 60%. CONCLUSIONS: 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.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blot W. J., Devesa S. S., Kneller R. W., Fraumeni J. F., Jr Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA. 1991 Mar 13;265(10):1287–1289. [PubMed] [Google Scholar]
- Boring C. C., Squires T. S., Tong T., Montgomery S. Cancer statistics, 1994. CA Cancer J Clin. 1994 Jan-Feb;44(1):7–26. doi: 10.3322/canjclin.44.1.7. [DOI] [PubMed] [Google Scholar]
- Fléjou J. F., Potet F., Muzeau F., Le Pelletier F., Fékété F., Hénin D. Overexpression of p53 protein in Barrett's syndrome with malignant transformation. J Clin Pathol. 1993 Apr;46(4):330–333. doi: 10.1136/jcp.46.4.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forastiere A. A., Orringer M. B., Perez-Tamayo C., Urba S. G., Husted S., Takasugi B. J., Zahurak M. Concurrent chemotherapy and radiation therapy followed by transhiatal esophagectomy for local-regional cancer of the esophagus. J Clin Oncol. 1990 Jan;8(1):119–127. doi: 10.1200/JCO.1990.8.1.119. [DOI] [PubMed] [Google Scholar]
- Harpole D. H., Jr, Herndon J. E., 2nd, Wolfe W. G., Iglehart J. D., Marks J. R. A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histopathology, and oncoprotein expression. Cancer Res. 1995 Jan 1;55(1):51–56. [PubMed] [Google Scholar]
- Herskovic A., Leichman L., Lattin P., Han I., Ahmad K., Leichman G., Rosenberg J., Steiger Z., Bendal C., White B. Chemo/radiation with and without surgery in the thoracic esophagus: the Wayne State experience. Int J Radiat Oncol Biol Phys. 1988 Sep;15(3):655–662. doi: 10.1016/0360-3016(88)90308-2. [DOI] [PubMed] [Google Scholar]
- Jankowski J., Coghill G., Hopwood D., Wormsley K. G. Oncogenes and onco-suppressor gene in adenocarcinoma of the oesophagus. Gut. 1992 Aug;33(8):1033–1038. doi: 10.1136/gut.33.8.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kavanagh B., Anscher M., Leopold K., Deutsch M., Gaydica E., Dodge R., Allen K., Allen D., Staub W., Montana G. Patterns of failure following combined modality therapy for esophageal cancer, 1984-1990. Int J Radiat Oncol Biol Phys. 1992;24(4):633–642. doi: 10.1016/0360-3016(92)90708-p. [DOI] [PubMed] [Google Scholar]
- Lackey V. L., Reagan M. T., Smith R. A., Anderson W. J. Neoadjuvant therapy of squamous cell carcinoma of the esophagus: role of resection and benefit in partial responders. Ann Thorac Surg. 1989 Aug;48(2):218–221. doi: 10.1016/0003-4975(89)90073-8. [DOI] [PubMed] [Google Scholar]
- MacFarlane S. D., Hill L. D., Jolly P. C., Kozarek R. A., Anderson R. P. Improved results of surgical treatment for esophageal and gastroesophageal junction carcinomas after preoperative combined chemotherapy and radiation. J Thorac Cardiovasc Surg. 1988 Mar;95(3):415–422. [PubMed] [Google Scholar]
- Marks J. R., Humphrey P. A., Wu K., Berry D., Bandarenko N., Kerns B. J., Iglehart J. D. Overexpression of p53 and HER-2/neu proteins as prognostic markers in early stage breast cancer. Ann Surg. 1994 Apr;219(4):332–341. doi: 10.1097/00000658-199404000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mercke C., Albertsson M., Hambraeus G., Tennvall J., Lillo-Gil R., Samuelsson L., Willén R., Ranstam J. Cisplatin and 5-FU combined with radiotherapy and surgery in the treatment of squamous cell carcinoma of the esophagus. Palliative effects and tumor response. Acta Oncol. 1991;30(5):617–622. doi: 10.3109/02841869109092429. [DOI] [PubMed] [Google Scholar]
- Motojima K., Furui J., Kohara N., Izawa K., Kanematsu T., Shiku H. erbB-2 expression in well-differentiated adenocarcinoma of the stomach predicts shorter survival after curative resection. Surgery. 1994 Mar;115(3):349–354. [PubMed] [Google Scholar]
- Muss H. B., Thor A. D., Berry D. A., Kute T., Liu E. T., Koerner F., Cirrincione C. T., Budman D. R., Wood W. C., Barcos M. c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med. 1994 May 5;330(18):1260–1266. doi: 10.1056/NEJM199405053301802. [DOI] [PubMed] [Google Scholar]
- Poplin E., Fleming T., Leichman L., Seydel H. G., Steiger Z., Taylor S., Vance R., Stuckey W. J., Rivkin S. E. Combined therapies for squamous-cell carcinoma of the esophagus, a Southwest Oncology Group Study (SWOG-8037). J Clin Oncol. 1987 Apr;5(4):622–628. doi: 10.1200/JCO.1987.5.4.622. [DOI] [PubMed] [Google Scholar]
- Popp M. B., Hawley D., Reising J., Bongiovanni G., Weesner R., Moomaw C. J., Martelo O., Aron B. Improved survival in squamous esophageal cancer. Preoperative chemotherapy and irradiation. Arch Surg. 1986 Nov;121(11):1330–1335. doi: 10.1001/archsurg.121.11.1330. [DOI] [PubMed] [Google Scholar]
- Ramel S., Reid B. J., Sanchez C. A., Blount P. L., Levine D. S., Neshat K., Haggitt R. C., Dean P. J., Thor K., Rabinovitch P. S. Evaluation of p53 protein expression in Barrett's esophagus by two-parameter flow cytometry. Gastroenterology. 1992 Apr;102(4 Pt 1):1220–1228. [PubMed] [Google Scholar]
- Sasano H., Miyazaki S., Gooukon Y., Nishihira T., Sawai T., Nagura H. Expression of p53 in human esophageal carcinoma: an immunohistochemical study with correlation to proliferating cell nuclear antigen expression. Hum Pathol. 1992 Nov;23(11):1238–1243. doi: 10.1016/0046-8177(92)90291-a. [DOI] [PubMed] [Google Scholar]
- Seydel H. G., Leichman L., Byhardt R., Cooper J., Herskovic A., Libnock J., Pazdur R., Speyer J., Tschan J. Preoperative radiation and chemotherapy for localized squamous cell carcinoma of the esophagus: a RTOG Study. Int J Radiat Oncol Biol Phys. 1988 Jan;14(1):33–35. doi: 10.1016/0360-3016(88)90047-8. [DOI] [PubMed] [Google Scholar]
- Stewart J. R., Hoff S. J., Johnson D. H., Murray M. J., Butler D. R., Elkins C. C., Sharp K. W., Merrill W. H., Sawyers J. L. Improved survival with neoadjuvant therapy and resection for adenocarcinoma of the esophagus. Ann Surg. 1993 Oct;218(4):571–578. doi: 10.1097/00000658-199310000-00017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolfe W. G., Burton G. V., Seigler H. F., Crocker I. R., Vaughn A. L. Early results with combined modality therapy for carcinoma of the esophagus. Ann Surg. 1987 May;205(5):563–571. doi: 10.1097/00000658-198705000-00016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolfe W. G., Vaughn A. L., Seigler H. F., Hathorn J. W., Leopold K. A., Duhaylongsod F. G. Survival of patients with carcinoma of the esophagus treated with combined-modality therapy. J Thorac Cardiovasc Surg. 1993 Apr;105(4):749–756. [PubMed] [Google Scholar]