Thyroid carcinomas of an additional series of 34 children exposed to radioactive fall-out after the Chernobyl reactor accident were analysed for mutations in the H-, K- and N-RAS and the p53 gene. Allele-specific oligonucleotide hybridization, single-strand conformation polymorphism (SSCP) and direct sequencing did not disclose mutations in codons 12, 13 and 61 of RAS genes nor mutations in exons 5, 7 and 8 of p53. Considering the recently reported high prevalence of RET rearrangements of the PTC3 type in childhood tumours after Chernobyl (Klugbauer et al, 1995, Oncogene 11: 2459-2467), it follows that RET rearrangements are the most relevant molecular aberration in these radiation-induced tumours. RAS or p53 mutations do not play a role in childhood thyroid carcinogenesis after Chernobyl.
Activating mutation in K-ras gene is a key event in the pathogenesis of colon carcinoma. This study analyses frequency of this mutation in different age groups of colorectal cancer patients residing in North-Western Russia, and examines its relationship with essential clinical characteristics of tumor disease.
We have examined restriction fragment length polymorphisms of the H-ras-1 gene in germ-line DNA from 214 lung cancer patients and 309 unaffected controls. When DNA samples were digested with MspI/HpaII, Southern blot analysis revealed at least 22 different alleles, grouped according to their frequencies as common, intermediate, and rare. The frequency of rare alleles in lung cancer patients (16/428) is significantly different (p = 0.002) from that in the control group (5/618). Individuals with rare alleles were found to be at 4.7-fold greater risk of lung cancer than those with no rare alleles.
After the nuclear accident of Chernobyl, in the population of zones contaminated the malignant renal tumors was increased from 4.7 to 7.5 per 100,000 of total population. Cesium 137 (137Cs) constitutes 80-90% of the internal exposure of these people as well as eliminated through kidneys becomes an important risk factor. We present a case of a patient, residing in radiocontamined area, who consulted for abdominal pain and left flank mass. We review relevant literature and the management of these patients.
The association of ability to grow in vitro, non-random chromosome abnormalities, DNA ploidy and oncogene amplification with prognosis may lead to a better understanding of the biology of neuroblastomas. In a pilot study fresh tumour tissue was obtained from 4 consecutive patients at the Department of Paediatric Surgery, Rigshospitalet, Denmark. Chromosome abnormalities were detected in 3 out of 3 successfully karyotyped tumours, and one or more aneuploid stem lines were detected in 4 out of 4 tumours using flow cytometry. The N-myc oncogene was amplified in 1 out of 3 tumours tested. Continuous cell lines could be established from all 3 advanced stage tumours. This pilot study has shown that fresh tumour tissue can be obtained and successfully studied for various fundamental aspects of the biology of neuroblastomas.
BACKGROUND: Increasing evidence suggests that a substantial proportion of colorectal carcinomas develop without a preexisting polypoid adenomatous lesion, but it is difficult to detect the possible origin of advanced carcinomas. The purpose of this study was to test the validity and significance of a new histopathologic classification system based on the histologic analysis of the tumor edge. METHODS: One hundred eighty-six unselected cases of colorectal carcinoma were included. A new classification method to distinguish polypoid and nonpolypoid growth type was based on the presence or absence of elevation of tumor as compared with adjacent mucosa. Inter- and intraobserver agreement of classification was tested. Association with other clinicopathologic features including histopathologic characteristics of the tumors, presence or absence of lesional and concurrent adenoma, K-ras mutations, and prognosis was evaluated. RESULTS: Classification could be made in 75% of the tumors, and 25% were unclassifiable, mostly due to absence of tumor margin in sections. Of the classifiable carcinomas, 45% were classified as polypoid, of which 52% had lesional adenoma. Nonpolypoid tumors formed 48% of classifiable cases, and only 2% had lesional adenoma. Features of both polypoid and nonpolypoid carcinomas were present in 7% of cases. Concurrent extralesional adenomas were found more frequently in association with polypoid carcinomas. K-ras mutations were more common in polypoid (43%) than in nonpolypoid tumors (8%; P = 0.018). Nonpolypoid carcinomas were significantly (P = 0.03) more aggressive than polypoid carcinoma, with 38% and 20% recurrence rates, respectively. CONCLUSIONS: The authors' results indicate that advanced colorectal carcinomas can be classified according to growth pattern by observing the tumor edge. This classification has prognostic significance because nonpolypoid carcinomas appeared to have a worse prognosis than polypoid ones.
Aim of the work is to estimate the role of the metastases molecular signs (MMS) in paraaortal lymphatic nodes, revealed using combined molecular-biological method with application of K-RAS markers and cytokeratine 20 (CK20) for the survival prognostication in the pancreatic head cancer patients after performing pancreatoduodenal resection. Actuarial index of general survival of the patients with MMS in paraaortal lymphatic nodes was trustworthy lower than in patients without such a signs. The two-year survival index in patients without MMS was 60%, the survival mediana--32 mo. Any of the patients with MMS did not survive two years, the survival mediana was 13 mo.
Codon 12 of the K-ras gene is a generally recognized example of a mutational hot spot. By the approach of gel retardation and specific antibodies, a double-stranded oligonucleotide corresponding to the codon 12 region of the mouse K-ras gene (from 20 to 50 bp with respect to the exon 1 start) was found to be a site for cooperative binding of the transcription factors GATA-6 and NF-Y. GATA-6 and NF-Y were selectively activated with lung carcinogens 3-methylcholanthrene and nitrosoethylurea in mice of strains susceptible to lung tumorigenesis but not in animals of resistant strains. The interaction of GATA-6 and NF-Y with the codon 12 region of the K-ras gene is suggested to be involved in the mechanism of lung carcinogenesis.
BACKGROUND, MATERIALS AND METHODS: The role of epithelial cell growth and neoplastic transformation on collagen formation and deposition in the extracellular matrix (ECM) was analyzed by culturing immortalized human epidermal cell lines and Ras-transformed benign and malignant clones on collagen gels as transplants. The lesions were analyzed for extent of growth and morphology of epithelial and mesenchymal components as well as synthesis and deposition of different collagens. RESULTS: Immortalized cell lines required up to 5 weeks of growth for a well-organized mesenchyme to develop; transplants of Ras-transformed benign clones needed 3 weeks and transplants of highly malignant clones only 2 weeks to form an organized stroma. In transplants of immortalized cells after 2 weeks of growth newly-synthesized collagen type I and type III were deposited in the mesenchyme adjacent to the muscle, forming a mature ECM, while ECM was absent adjacent to growing, differentiated, immortalized cells. In transplants of Ras-transformed benign clones the subepithelial ECM was immature at day 14, but it was forming fibers at the same time in transplants of malignant clones. These were seen as thin irregular fibers in immunohistochemistry, ultimately organized into fibrillar structures in similar locations to active synthesis detected by in situ hybridization. Depositions of crosslinked mature type I collagen occurred later in similar locations. Type III collagen synthesis and deposition was most prominent in transplants of malignant cell clones, with degradation and destruction of the extracellular matrix around invading islets of malignant cells. CONCLUSION: The development of mesenchyme was directly related to duration of growth of transplants and degree of malignancy; mesenchyme organization was inversely related to differentiation of the epithelial cells. The results showed the usefulness of the transplant model in studies on cell and tissue growth and organization.
Colorectal cancer is one of the most common malignancies in Norway. Many cases of the disease are detected at a stage where surgery is unlikely to result in cure. Currently used screening tests based on faecal occult blood and other tumour markers are poor indicators of colorectal neoplasia. Multiple gene alterations are associated with colorectal carcinogenesis. Mutations in the Ki-ras oncogene occur in 50% of colorectal carcinomas and also in 50% of the precursor lesions, the adenomas. These mutations have proved to be detectable in the faeces of patients with colorectal tumours, but the techniques used so far have been impractical for screening purposes. We have developed a rapid and simple laboratory technique, based on the polymerase chain reaction, for detecting mutated Ki-ras in the faeces. In eight of 12 patients with mutated Ki-ras in adenomas or carcinomas we found the corresponding mutations in stool samples. Our results represent a significant progression towards a simple and effective DNA-based screening strategy for early detection of curable colorectal cancer.