Spinal muscular atrophy (SMA) is characterized by degeneration of lower motor neurons caused by mutations of the survival motor neuron 1 gene (SMN1). SMN is involved in various processes including the formation of the spliceosome, pre-mRNA splicing and transcription. To know whether SMN has an essential role in all mammalian cell types or an as yet unknown specific function in the neuromuscular system, deletion of murine Smn exon 7, the most frequent mutation found among SMA patients, has been restricted to liver. Homozygous mutation results in severe impairment of liver development associated with iron overload and lack of regeneration leading to dramatic liver atrophy and late embryonic lethality of mutant mice. These data strongly suggest an ubiquitous and essential role of full-length SMN protein in various mammalian cell types. In SMA patients, the residual amount of SMN allows normal function of various organs except motor neurons. However, data from mouse and human suggest that other tissues might be involved in severe form of SMA or during prolonged disease course which reinforce the need of therapeutic approaches targeted to all tissues. In addition, liver function of patients should be carefully investigated and followed up before and during therapeutic trials.

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The pathological findings of 26 consecutive resections for hepatocellular carcinomas developing in cirrhotic patients were analyzed morphologically with a special interest in the presence of a capsule, vascular extension and satellite nodules. Tumor sizes varied from 2 to 11 cm. There were 20 expanding (76.9%) and six infiltrating tumors. Infiltrating tumors were significantly larger than expanding tumors (p less than 0.01). Histologically, the most common subgroups were the trabeculated pattern (65.4%) and the Edmonson-Steiner Type II (53.9%). Of the 20 expanding tumors, only six had direct spread in the liver parenchyma adjacent to the tumor (p less than 0.02). There was a significant relationship between the presence of a tumor extension in the distal portal branches and the presence of satellite nodules around the tumor (p less than 0.01). Survival at 6 months was significantly lower in patients with infiltrating (16.7%) than in those with expanding tumors (75%), (p less than 0.05). The present results indicate that pathological features of hepatocellular carcinomas in cirrhotic patients in Western countries are similar to those encountered in the East: (a) tumors are frequently encapsulated; (b) the propensity for the tumor to spread is closely related to the presence of a tumor capsule. This study suggests that a thorough preoperative search for the capsule should be made whenever resection of a hepatocellular carcinoma in a cirrhotic patient is contemplated.

Insulin-like growth factor II is a fetal growth factor structurally and functionally related to insulin and insulin-like growth factor I. Its mRNA expression is developmentally regulated in human liver, the reexpression of insulin-like growth factor II fetal transcripts being often observed in primary liver cancer. Insulin-like growth factor II and alpha-fetoprotein mRNAs were studied in 16 human primary liver cancers, most of which were highly differentiated. Hepatitis B virus transcripts were also analyzed in the tumors from hepatitis B virus chronic carriers. alpha-Fetoprotein mRNA was detected in only four tumors and in one nontumorous cirrhotic tissue; all these samples also displayed insulin-like growth factor II fetal transcripts. Furthermore, fetal insulin-like growth factor II mRNAs were observed in five tumors and six nontumorous cirrhotic areas not expressing alpha-fetoprotein mRNA. The presence of hepatitis B virus RNA was only observed in tissues not expressing alpha-fetoprotein or fetal insulin-like growth factor II mRNA. In conclusion, fetal insulin-like growth factor II transcripts are more frequently observed than alpha-fetoprotein mRNA in highly differentiated liver cancers and in surrounding cirrhotic areas. The reexpression of fetal insulin-like growth factor II transcripts might then be a marker of early steps of liver cell transformation.