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ALK gene has been identified as a major neuroblastoma (NBL) predisposition gene. But ALK gene copy number and protein expression in ganglioneuroblastoma (GNBL) and ganglioneuroma (GN) are poorly described in the literature. Furthermore, there are controversies on the correlation between ALK protein expression and clinical outcome in NBL.We evaluated MYCN/ALK gene copy number by fluorescence in situ hybridization (FISH) and detected ALK protein expression by immunohistochemistry (IHC) in 188 NBL, 52 GNBL and 6 GN samples and analyzed their association with clinical outcome of the patients.Although ALK gene copy number increase is a recurrent genetic aberration of neuroblastic tumors (NTs) (39.1%, 96/246), ALK amplification was only present in three NBLs (1.2%, 3/246). The frequency of ALK positivity in NBL (50.5%, 51/101) was significantly higher than in GNBL (22.6%, 7/31) and in GN (0.0%, 0/4) (P0.05). In addition, ALK positivity also significantly correlates with MYCN/ALK gene copy number increases (P0.05). Kaplan-Meier survival analysis indicated that MYCN/ALK amplification is correlated with decreased overall survival in NBL. A better prognosis trend was observed in patients with MYCN/ALK gain tumors compared with those with MYCN/ALK normal tumors. Furthermore, ALK positivity significantly correlated with inferior survival in NBL (P=0.044).ALK positivity in NTs correlated with advanced tumor types and MYCN/ALK gene copy number increases. ALK positivity predicts inferior prognosis in NBL and IHC is a simplified strategy to screen ALK positivity in clinical practice.

Anthracosis is the deposition of black dusty material in the pulmonary parenchyma. Previous reports showed anthracosis and p16(ink4a) gene aberrant methylation are closely related to the promotion and progression of small-sized pulmonary adenocarcinoma. In this study, we investigated the influence of anthracosis and p16(ink4a) gene aberrant methylation on clinical samples from patients with small-sized adenocarcinoma.DNA was bisulfite modified and methylation-specific PCR was performed to detect p16(ink4a) gene aberrant methylation; black dusty material was extracted from lung tissues. Anthracotic index (AI) was defined as the absolute absorbance by densitometry. The histopathological diagnosis was concluded according to Noguchi's classification for small-sized pulmonary adenocarcinoma. The mean AI and the frequency of p16(ink4a) gene aberrant methylation of heavy smokers were significantly higher than that of nonsmokers (Ｐ0.01 andＰ0.05, respectively). The frequency of p16(ink4a) gene aberrant methylation of early stage small-sized adenocarcinoma was lower than that of advanced and poorly differentiated, while p16(ink4a) protein expression level of early stage small-sized adenocarcinoma was significantly higher than that of poorly differentiated small-sized adenocarcinoma (P0.05).AI and p16(ink4a) gene aberrant methylation may provide a potential universal biomarker for small-sized adenocarcinoma.