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The prevalence of human liver cancer shows a broad spectrum of variation in distinct geographical regions, depending on different risk factors, and their pathogenesis is poorly understood. We study the significance of molecular alterations of K-ras gene in human liver carcinomas in a low-incidence region such as a Mediterranean area of Spain (Valencia and Gerona). Our results reveal a low incidence of K-ras codon 12 mutations in hepatocellular carcinomas (HCC) and a higher incidence in cholangiocarcinomas (CCC). Similar results have been obtained in high-risk areas. We conclude that K-ras gene mutations are not a major event in the malignant transformation of hepatic cells in this region of the Mediterranean but that molecular implications of hepatocellular and cholangiocarcinomas appear to be different. Int J Surg Pathol 8(4):267-270, 2000

N-myc gene amplification and/or loss of heterozygosity of chromosome 1 (LOH lp) are important criteria for prognosis and progression in human neuroblastoma (NB). Despite the high incidence of alterations of the p53 gene in human cancers, very few p53 mutations have been reported in NB. The objective of our study was to search for p53 mutations in NB and their correlation with N-myc amplification and clinical or pathologic parameters. We analyzed 14 selected cases of NB from the Spanish Protocol N-II-92. We found a missense mutation in codon 248 CGG to GGG (Arg/Gly) in one case of stage 4 NB with no N-myc amplification. Our results confirm the low incidence of p53 gene mutation in neuroblastoma and the absence of correlation with histopathologic parameters.

Small cell sarcomas of bone are difficult to classify and diagnose. The present case deals with such a tumor in which the original biopsy and the resected specimen, studied by histology before chemotherapy, provided no final information about its real nature. Thus several techniques were applied to discern its histogenesis and biology. Myogenin proved positive in isolated cells of the primary neoplasm but was extensively expressed in nude mice xenografts. Electron microscopy confirmed the existence of myofilaments. The cytogenetic analysis revealed a large number of chromo somal abnormalities, but not those found in the Ewing's/PNET (peripheral neuroectodermal tumor) family of tumors. This was confirmed by polymerase chain reaction (RT-PCR) wherein no EWS/Fli 1 or PAX3/FKHR gene rearrangements were detected. Based upon these studies, a rhabdomyosarcoma of bone was diagnosed. Clinically the neoplasm showed a highly aggressive behavior, causing death of the patient within 2 years after diagnosis.

Gastrointestinal stromal tumors (GISTs) are c-KIT-signaling-driven mesenchymal tumors of the human digestive tract, many of which have c-KIT or PDGFRα activating mutations. The authors studied the immunohistochemical markers, c-KIT and PDGFRα mutations, in GISTs and their association with the clinicopathological and clinical follow-up in 145 GISTs. Tumors were located mainly in the stomach, the median tumor size being 7.5 cm. The mitotic index was ≤5 mitoses per 50 high-power fields in 61% of cases, 96% expressed CD117, and c-KIT or PDGFRα mutations were detected in 68% of cases. The median follow-up of the series was 52 months (range = 1 to 244.9 months). Tumor size, cell morphology, mitotic index, incomplete resection, Fletcher’s risk classification, Ki-67 overexpression, and c-KIT mutations were associated with progression-free survival. Incomplete resection and mitotic activity also provide information about overall survival. In conclusion, complete clinicopathological, immunohistochemical, and genetic descriptions are necessary to characterize this disease and optimize its clinical management.