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Expression of apoptosis-related proteins and response to chemoradiotherapy and prognosis in esophageal cancer

Expresión de proteinas implicadas en la apoptosis y su relación con la respuesta a la quimiorradioterapia y al pronóstico en el cáncer de esófago

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Abstract

Purpose

Defects in the apoptotic pathway confer insensitiviry to the cytotoxic effects of chemotherapy and hence represent an important distal mechanism for the development of chemoresistance. In this study, we sought to obtain results on which to base clinical hypotheses about this mechanism. The aim of this study was to analyze the correlation of the expression of three of these apoptotic molecules, Bc1-2, Bax and Bc1-X, with chemoradiotherapy response and clinical outcome in patients with esophageal tumors.

Patients and methods

Tumor biopsy specimens from 42 patients were assessed by immunohistochemistry for expression of Bc1-2, Bax and Bc1-X proteins. The expression of these proteins was correlated with response to chemoradiotherapy in 24 patients.

Results

The overall expression of Bc1-2, Bax and Bc1-X was 29%, 68% and 88%, respectively. Bax expression was lower in lymph-node-positive tumors (p = 0.01). Probability of response to chemoradiotherapy was higher in Bax-negative tumors than in Bax-positive tumors (80% vs 35%, p = 0.1). In addition, 62% of patients with low Bc1-X expression (< 50% stained cells) showed response to chemoradiotherapy, as opposed to only 33% of patients with higher Bc1-X expression (p = 0.2). Patients with low Bc1-X expression showed a significantly better prognosis than those with high Bc1-X expression (p =0.02), and a tendency towards higher survival was detected in Bc1-2 positive patients.

Conclusion

The correlation detected between Bax and Bc1-X expression and response to chemoradiotherapy suggests that screening for these apoptosisrelated proteins could be useful in determining patients who would benefit from chemoradiotherapy. However, further investigation is warranted to elucidate the potential role of Bax in taxane-treated patients. Clearly, since high Bc1-X expression conferred poor survival in our study, it could be a useful prognostic marker in esophageal cancer.

Resumen

Propósito

Las alteraciones en el patrón de apoptosis confieren insensibilidad a los efectos citotóxicos de la quimioterapia y representan un importante mecanismo en el desarrollo de quimiorresistencia. Este estudio se ha realizado para analizar el papel que desempefian los mecanismos de apoptosis en la práctica clínica. El objetivo del estudio fue establecer la correlación entre la expresión de Bcl-2, Bax y Bcl-X con la respuesta a la quimiorradioterapia y el pronósitco en pacientes con cancer de esófago.

Pacientes y métodos

Se han analizado, mediante inmunohistoquímica, las biopsias de 42 pacientes para determinar la expresión de las proteínas Bcl-2, Bax y Bcl-X. En 24 de estos pacientes la expresión de estas proteínas se correlacionó con la respuesta a quimiorradioterapia.

Resultados

La expresión de Bcl-2, Bax y Bcl-X se detectó en un 29, un 68 y un 88% de los tumores, respectivamente. La expresión de Bax fue inferior en tumores con afectación de los ganglios linfáticos (p = 0,01). La probabilidad de respuesta a la quimiorradioterapia fue superior en los tumores Bax negativos respecto a los positivos para dicha proteína (80 y 35%, respectivamente; p = 0,1). El 62% de pacientes con expresión baja de Bc1-X (< 50% de células teñidas) respondieron al tratamiento con quimiorradioterapia; por el contrario, sólo un 33% de los pacientes con expresión elevada de Bcl-X respondieron al tratamiento (p = 0,2). En los pacientes con expresión baja de Bcl-X el pronóstico fue significativamente mejor que en los pacientes con expresión elevada (p = 0,02); así mismo, los pacientes con tumores con expresión de Bcl-2 demostraron una tendencia a una supervivencia mejor.

Conclusiones

La relación entre la expresión de Bax y Bcl-X y la respuesta a la quimiorradioterapia sugiere que el estudio de las proteínas relacionadas con la apoptosis podría ser de utilidad para deter — minar qué pacientes pueden beneficiarse de dicho tratamiento. Se requieren más estudios para definir el papel de la proteína Bax en los pacientes tratados con taxanos. En nuestro estudio, la expresión elevada de Bcl-X se correlacionó con un peor pronóstico y, por tanto, podría ser un marcador pronóstico en el cáncer de esófago.

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Authors and Affiliations

  1. Department of Medical Oncology, Hospital Germans Trias i Pujol, Badalona, Spain

    Albert Font & Rafael Rosell

  2. Departments of Medical Oncology, Dartmouth Hitchcock Medical Center, 03756-0001, Lebanon, NH

    James R. Rigas

  3. Departments of Molecular Therapeutics, Dartmouth Hitchcock Medical Center, 03756-0001, Lebanon, NH

    Alan Eastman

  4. Departments of Pathology, Dartmouth Hitchcock Medical Center, 03756-0001, Lebanon, NH

    Vincent A. Memoli

  5. Departments of Biostatistics, Dartmouth Hitchcock Medical Center, 03756-0001, Lebanon, NH

    Bernard F. Cole

  6. Departments of Data Coordination, Dartmouth Hitchcock Medical Center, 03756-0001, Lebanon, NH

    Sue Hammond

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  1. Albert Font
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  2. James R. Rigas
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  7. Rafael Rosell
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Correspondence to James R. Rigas.

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Font, A., Rigas, J.R., Eastman, A. et al. Expression of apoptosis-related proteins and response to chemoradiotherapy and prognosis in esophageal cancer. Rev Oncología 2, 146–153 (2000). https://doi.org/10.1007/BF02979482

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