PubMed:9028739 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/9028739","sourcedb":"PubMed","sourceid":"9028739","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/9028739","text":"Clinicopathologic analysis of k-ras, p53, and ERBB-2 gene alterations in pulmonary adenocarcinoma.\nWe compared PCR-SSCP detected mutations of k-ras (codon 12) and p53 (exons 5-8) to ERBB-2 immunostaining and clinicopathologic features in 31 pulmonary adenocarcinomas. There were nine tumors (29%) with mutations of ras, 13 tumors (42%) with mutations of p53, and three tumors (10%) with mutations of both. Neither k-ras nor p53 mutation alone was significantly correlated with stage, grade, or survival. However, tumors with k-ras mutation were more frequently associated with an invasive growth pattern, defined as \u003e 30% tumor volume composed of infiltrative nests of cells within desmoplastic, scar-like stroma [\u003c 30% volume invasive--1/13 (8%) with k-ras mutation vs. \u003e 30% volume invasive--8/18 (44%) with k-ras mutation, p = 0.02]. Accordingly, k-ras mutations were observed in only 1/9 (15%) predominantly bronchoalveolar or papillary tumors versus 6/22 (28%) acinar or scar carcinoma tumors. All three patients with combined k-ras/p53 mutation had advanced stage (III/IV) at presentation and died of the disease. In contrast to k-ras, staining for ERBB-2 was more frequently observed in tumors exhibiting \u003c 30% invasive growth pattern (12/13, 92%) than in tumors with \u003e 30% invasive growth pattern (10/18, 56%, p = 0.03). ERBB-2 immunoreactivity was more frequent in Stage I (14/15, 93%) versus Stage II-IV (8/16, 50%) cases, but it did not correlate with survival. There was a reciprocal relationship between k-ras mutation and ERBB-2 staining; only 4/9 (44%) k-ras mutated cases were ERBB-2 positive versus 18/22 (82%) cases without k-ras mutation (p = 0.005). In contrast, 8/13 cases with p53 mutation were ERBB-2 positive. We conclude that well-differentiated and less invasive papillary and bronchoalveolar tumors are more often ERBB-2 positive/k-ras negative (i.e. at codon 12), whereas less well differentiated acinar or scar carcinomas are more often ERBB-2 negative/k-ras mutated at codon 12. These findings imply that the divergent histogenesis of pulmonary adenocarcinoma may reflect specific differences in genetic pathology.","tracks":[{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":46,"end":52},"obj":"gene:2064"},{"id":"T1","span":{"begin":83,"end":97},"obj":"disease:C0001418"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"9028739-0#46#52#gene2064","span":{"begin":1329,"end":1335},"obj":"gene2064"},{"id":"9028739-0#83#97#diseaseC0001418","span":{"begin":2032,"end":2089},"obj":"diseaseC0001418"},{"id":"9028739-1#64#67#gene7157","span":{"begin":163,"end":166},"obj":"gene7157"},{"id":"9028739-1#152#167#diseaseC0001418","span":{"begin":251,"end":266},"obj":"diseaseC0001418"}],"relations":[{"id":"46#52#gene206483#97#diseaseC0001418","pred":"associated_with","subj":"9028739-0#46#52#gene2064","obj":"9028739-0#83#97#diseaseC0001418"},{"id":"64#67#gene7157152#167#diseaseC0001418","pred":"associated_with","subj":"9028739-1#64#67#gene7157","obj":"9028739-1#152#167#diseaseC0001418"}],"attributes":[{"subj":"9028739-0#46#52#gene2064","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"9028739-0#83#97#diseaseC0001418","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"9028739-1#64#67#gene7157","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"9028739-1#152#167#diseaseC0001418","pred":"source","obj":"DisGeNET5_gene_disease"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET","color":"#93c4ec","default":true},{"id":"DisGeNET5_gene_disease","color":"#deec93"}]}]}}