RESUMEN
PURPOSE: To investigate the expression of sex steroid receptors in gastric cancer and to correlate their tumor expression profile with the clinicopathological parameters and overall survival of the patients. METHODS: Immunohistochemical methodology was employed in formalin-fixed paraffin-embedded sections from 86 patients with gastric carcinoma. Monoclonal antibodies against androgen (AR), estrogen (ER), and progesterone (PR) receptors were used. Survival rates were estimated by the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed by the Cox proportional hazards model. RESULTS: Fifteen (17.4%) cases of gastric adenocarcinomas were positive for AR, two (2.3%) were positive for PR and three (3.5%) were positive for ER. Significantly higher AR expression was found in tumors with metastases to lymph nodes (P = 0.03). Patients with AR-positive tumors (AR+) had worse prognosis than (AR-) patients (median survival 9 months vs 24 months, P = 0.03). Patients with AR- and heat shock protein 27 (HSP27)-positive tumors (AR+/HSP27+) had a median survival of 6 months, whereas (AR-/HSP27-) patients had a median survival of 42 months (P = 0.017). Multivariate analysis revealed that AR expression and UICC stage were independent factors of unfavorable prognosis (P = 0.037 and P = 0.0055, respectively). CONCLUSIONS: Identification of AR-positive gastric carcinomas in gastric biopsies may warrant a more aggressive therapeutic approach and anti-androgen or AR-targeted agents may represent a novel strategy in tackling this devastating malignancy.
Asunto(s)
Metástasis Linfática/patología , Receptores Androgénicos/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Femenino , Proteínas de Choque Térmico HSP27 , Proteínas de Choque Térmico/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Chaperonas Moleculares , Proteínas de Neoplasias/metabolismo , Estadificación de Neoplasias , Pronóstico , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
PURPOSE: The investigation of heat shock protein 27 (HSP27) expression in gastric cancer and adjacent normal, metaplastic, and dysplastic gastric mucosa and its correlation with clinicopathological parameters and survival of patients. METHODS: Immunohistochemical methodology was performed on formalin-fixed paraffin-embedded sections by using a monoclonal anti-HSP27 antibody. HSP27 expression was screened and compared in 86 cases of gastric carcinoma and adjacent normal, metaplastic, and dysplastic gastric mucosa. RESULTS: In the normal mucosa, HSP27 was detected in 68 out of 86 cases (79%) and was more intense in the surface and upper two-thirds of gastric foveolae. In dysplastic gastric mucosa, HSP27 immunoreactivity was usually higher than that of the adjacent normal epithelium and was parallel to the severity of dysplasia. HSP27 expression was found in 54 out of 86 (62.7%) gastric carcinomas and was significantly related to more than six metastatic lymph nodes ( P =0.03). HSP27 expression was also higher in tumors of advanced stage and in those of female patients. HSP27 expression was associated with shorter overall survival in univariate analysis ( P =0.04), but this relationship was not retained in multivariate analysis. CONCLUSIONS: Our findings indicate that: i) HSP27 is commonly expressed in normal gastric epithelium where it seems to exert a protective role; and ii) HSP27 is involved in gastric carcinogenesis and its expression appears to be associated with parameters of unfavorable prognosis and shorter overall survival.
