RESUMEN
The purpose of this study is to investigate the relationship between mutation status, copy number, and protein expression of epidermal growth factor receptor (EGFR) in lung adenocarcinoma, and to correlate the genetic status and clinicopathologic features. Forty-nine adenocarcinomas were tested by polymerase chain reaction (PCR) for EGFR gene mutations, by fluorescence in situ hybridization (FISH) for increased EGFR gene copy number, and by immunohistochemistry (IHC) for EGFR protein expression. Terminal respiratory unit (TRU) morphology, tumor grade, mitotic count, and pleural and lymphovascular invasion were also examined. Five of 49 tumors (10%) had EGFR mutation by PCR. Eighteen (36%) had high EGFR gene copy number by FISH, all of which were polysomies without gene amplification. Fifteen (31%) had EGFR protein overexpression by IHC, 13 (87%) of which were also positive by FISH. Of the PCR-positive cases, 4/5 (80%) were positive by FISH and 3/5 (60%) were positive by IHC. TRU morphology was observed in all PCR-positive cases and in about 50% of FISH-positive and IHC-positive cases. Pleural invasion was significantly more common in IHC and FISH-positive cases, and lymphovascular invasion was more often present in FISH-positive cases. No statistically significant differences in mitotic count, age, sex, smoking status, degree of differentiation, or stage were seen. Our findings suggest that a staged approach, with FISH testing as the first step, followed by PCR for the FISH-negative cases would be most effective in the identification of patients with EGFR gene alterations.
Asunto(s)
Adenocarcinoma/patología , Receptores ErbB/biosíntesis , Receptores ErbB/genética , Inmunohistoquímica/métodos , Hibridación Fluorescente in Situ/métodos , Neoplasias Pulmonares/patología , Reacción en Cadena de la Polimerasa/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Dosificación de Gen , Expresión Génica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , MutaciónRESUMEN
Although pulmonary meningothelial-like nodules (MLNs) have been recognized for decades, their nature and significance remain uncertain. This study was undertaken to evaluate MLNs in a wide range of specimens to clarify their incidence, distribution, relation to age and underlying disease, and histogenesis. Five hundred surgical lung biopsies, 25 extensively sampled lobectomies, 20 resections for pneumothoraces in persons younger than 30 years, and 92 pediatric autopsies were examined. Immunohistochemistry was performed in selected cases. One hundred eighty-six MLNs were identified in 81 cases, including 69 of 500 (13.8%) surgical biopsies and 12 of 25 (48%) lobectomies. No MLNs were found in pneumothorax resections or pediatric autopsies. Patients ranged from 22 to 84 years (mean, 62), with only 4 younger than 40 years. There were 56 women and 25 men (female:male=2.2:1). The highest incidence of MLNs was in thromboembolic disease/infarcts (5/12; 42%) and respiratory bronchiolitis-associated interstitial lung disease/desquamative interstitial pneumonia (9/35; 26%). MLNs were randomly distributed in alveolar septa with no consistent relation to small blood vessels. Immunohistochemistry demonstrated positivity for CD56 (18/18) in addition to progesterone receptor (18/18), epithelial membrane antigen (11/11), and vimentin (2/2). The high incidence of MLNs in our study may be related to underlying chronic lung disease. The finding of MLNs in almost half of extensively sampled lobectomies suggests that they may be present in all abnormal lungs if sufficiently sampled. Their absence in infants and children indicates that they are not congenital rests. The positive staining for CD56 is novel, and as CD56 has been reported in meningiomas, this finding supports meningothelial differentiation.