Ultrastructural features and platelet-derived growth factor receptor A gene mutations in CD117-negative gastrointestinal stromal tumor / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the ultrastructural features and mutation status of platelet-derived growth factor receptors A (PDGFRA) and c-kit in gastrointestinal stromal tumors that were immunohistochemically negative for CD117 antigen.</p><p><b>METHODS</b>Six cases of gastrointestinal stromal tumors that were CD117 immunostain negative were studied by electron microscopy. Direct PCR sequencing was used to investigate the mutation status of c-kit gene exons 9, 11, 13, 17 and PDGFRA gene exons 12 and 18.</p><p><b>RESULTS</b>The ultrastructural features of all 6 cases were similar to those of the interstitial cell of Cajal (ICC). None of the 6 cases were found to have c-kit gene mutations. However, three tumors were found to harbor PDGFRA exon 18 activating mutations, including two tumors having an Asp-->Val842 missense mutation and one having an Arg-->Ser841 missense mutation.</p><p><b>CONCLUSIONS</b>PDGFRA mutations may provide an important alternative molecular mechanism for the development of gastrointestinal stromal tumor.</p>

The clinical significance of p16 protein non-expression and p16 gene inactivation by deletions and hypermethylation in nasopharyngeal carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinical significance of p16 protein non-expression and p16 gene inactivation by deletions and hypermethylation in nasopharyngeal carcinoma.</p><p><b>METHODS</b>Immunohistochemical study for p16 protein was carried out in 90 cases of non-keratinizing carcinoma (NKC) of nasopharynx. P16 gene deletions and hypermethylation were also analyzed by polymerase chain reaction (PCR) and methylation-specific PCR in 23 randomly selected NKC cases.</p><p><b>RESULTS</b>Among the 90 NKC cases studied, 42 cases (46.7%) were negative for p16 protein. The non-expression rate of p16 protein also correlated with the 5-year survival rate. The non-expression rate was 60.0% in patients who died within 5 years, in contrast to 20.0% in those alive for over 5 years after diagnosis. The non-expression rate of p16 protein in cases with or without distant metastasis was 81.8% and 41.8% respectively (P < 0.05), while that in cases with or without local invasion into skull base was 41.7% and 48.5% respectively (P > 0.05). As for molecular analysis, deletion of p16 gene exon 2 was found in 10 of the 23 cases (43.4%) studied, while deletion of p16 gene exon 1 was not detected in these samples. Hypermethylation of p16 gene exon 1 was also noted in 2 of the 23 cases (8.7%). The overall mutation rate of these cases was 52.1%.</p><p><b>CONCLUSIONS</b>There is a high incidence of p16 protein non-expression, deletion of p16 gene exon 2 and hypermethylation of p16 gene exon 1 in NKC. P16 gene inactivation may thus play an important role in the pathogenesis of NKC, especially in terms of its metastatic potential.</p>