[Prognostic value of ERBB2 amplification and protein expression in small cell lung cancer]. / Valor pronóstico de la expresión y amplificación genética de c-erbB-2 en el carcinoma microcítico de pulmón.

OBJECTIVE: Our objective was to evaluate ERBB2 oncogene amplification using fluorescence in situ hybridization (FISH) and protein overexpression using immunohistochemical techniques, and to explore their possible prognostic value in a series of patients with small cell carcinoma. PATIENTS AND METHODS: Included in the study were 99 patients with small cell tumors, classified in 2 broad groups: patients with limited locally advanced disease and patients with disseminated disease. Material for study was obtained in 97% of the cases (96/99) by means of endoscopic biopsy and by tomography-guided needle biopsy in the remaining 3% (3/99). Survival was analyzed using the Kaplan-Meier method. RESULTS: The 92 men (92.9%) and 7 women (7.1%) in the study had a mean (SD) age of 62.9 (10.4) years (range, 36-81 years); 39.4% (n=39) and 60.6% (n=60) of the subjects had limited and disseminated disease, respectively. ERBB2 protein overexpression was observed in 26.3% of the patients (n=26), 15.4% (n=4) of whom had limited disease and 84.6% (n=22) of whom had disseminated disease (P=.005). Although mean survival was slightly longer for patients who were negative for ERBB2 protein overexpression, the difference was not statistically significant. FISH identified gene amplification in 6.3% (1 in 16) of the studied cases (ratio, 2.3). CONCLUSIONS: The protein product of the ERBB2 oncogene is overexpressed in 33.3% of small cell lung carcinomas and is associated with the presence of disseminated disease. Further studies are necessary to evaluate the possible benefits of specific treatment.

Lung carcinoma with rhabdoid component. A series of seven cases associated with uncommon types of non-small cell lung carcinomas and alveolar entrapment.

Rhabdoid tumor, included in the WHO classification among large cell carcinomas of the lung, is an uncommon type of lung carcinoma with poor prognosis. We report a series of 7 cases of lung carcinomas with rhabdoid component in 10% and 80% of the tumor. The associated tumor was adenocarcinoma in 3 cases--one of them with focal micropapillary pattern--large cell carcinoma in 2 cases, squamous cell carcinoma in 1 case and pleomorphic carcinoma in 1 case. Two adenocarcinomas showed a focal spindle cell component. Micropapillary and pleomorphic types had not been reported before as a component associated with rhabdoid carcinomas. All cases were positive for vimentin, and AE1/AE3 cytokeratin and 5 cases for cytokeratin 7. All cases were negative for muscle and endothelial markers and for chromogranin A. Synaptophysin was focally positive only in one case. Alveolar trapping inside the tumor was present in 3 cases--a phenomenon not well studied in lung carcinomas and also not reported in tumors with rhabdoid component. Five patients died because of the tumor within 2 to 31 months after diagnosis, one of myocardial infarction and only one is alive and disease free 123 months after the diagnosis. In summary, we describe 7 new cases of this uncommon lung tumor with aggressive clinical course, associated with infrequent histological types in nonrhabdoid component and with alveolar trapping, a nondescribed finding.

Valor pronóstico de la expresión y amplificación genética de c-erbB-2 en el carcinoma microcítico de pulmón / Prognostic value of ERBB2 amplification and protein expression in small cell lung cancer

Objetivo: El propósito de nuestro estudio ha sido evaluar la sobreexpresión proteica de c-erbB-2 mediante técnicas de inmunohistoquímica y la amplificación del oncogén mediante hibridación in situ fluorescente, en una serie de carcinomas microcíticos, correlacionándola con las posibles implicaciones pronósticas. Pacientes y métodos: Se incluyó a 99 pacientes con tumores microcíticos clasificados en 2 grandes grupos: enfermedad limitada o localmente avanzada y enfermedad diseminada. El material para estudio se obtuvo mediante biopsia endoscópica en el 97% de los casos (96/99) o mediante punción guiada por tomografía computarizada en el 3% restante (3/99). La supervivencia se analizó con el método de Kaplan-Meier. Resultados: La media de edad ± desviación estándar de los pacientes fue de 62,9 ± 10,4 años (rango: 36-81). El 92,9% (n = 92) eran varones y el 7,1% mujeres (n = 7). Un 39,4% (n = 39) presentaba enfermedad limitada y el 60,6% (n = 60) enfermedad diseminada. La sobreexpresión proteica de c-erbB-2 se observó en el 26,3% de los casos (n = 26), de los cuales un 15,4% (n = 4) presentaba enfermedad limitada y el 84,6% restante (n = 22) enfermedad diseminada (p = 0,005). La media de supervivencia fue ligeramente mayor para los pacientes con c-erbB-2 negativo que en aquéllos con c-erbB-2 positivo, pero esta diferencia no fue estadísticamente significativa. La técnica de hibridación in situ fluorescente mostró amplificación génica en el 6,3% (1/16) de los casos estudiados, con un índice de 2,3. Conclusiones: El producto proteico del oncogén c-erbB-2 se sobreexpresa en un 33,3% de los carcinomas microcíticos pulmonares y se asocia a la presencia de enfermedad diseminada. Son necesarios nuevos estudios para evaluar el posible beneficio del tratamiento específico

Objective: Our objective was to evaluate ERBB2 oncogene amplification using fluorescence in situ hybridization (FISH) and protein overexpression using immunohistochemical techniques, and to explore their possible prognostic value in a series of patients with small cell carcinoma. Patients and methods: Included in the study were 99 patients with small cell tumors, classified in 2 broad groups: patients with limited locally advanced disease and patients with disseminated disease. Material for study was obtained in 97% of the cases (96/99) by means of endoscopic biopsy and by tomography-guided needle biopsy in the remaining 3% (3/99). Survival was analyzed using the Kaplan-Meier method. Results: The 92 men (92.9%) and 7 women (7.1%) in the study had a mean (SD) age of 62.9 (10.4) years (range, 36-81 years); 39.4% (n=39) and 60.6% (n=60) of the subjects had limited and disseminated disease, respectively. ERBB2 protein overexpression was observed in 26.3% of the patients (n=26), 15.4% (n=4) of whom had limited disease and 84.6% (n=22) of whom had disseminated disease (P=.005). Although mean survival was slightly longer for patients who were negative for ERBB2 protein overexpression, the difference was not statistically significant. FISH identified gene amplification in 6.3% (1 in 16) of the studied cases (ratio, 2.3). Conclusions: The protein product of the ERBB2 oncogene is overexpressed in 33.3% of small cell lung carcinomas and is associated with the presence of disseminated disease. Further studies are necessary to evaluate the possible benefits of specific treatment