Patterns of p53 mutations separate ovarian serous borderline tumors and low- and high-grade carcinomas and provide support for a new model of ovarian carcinogenesis: A mutational analysis with immunohistochemical correlation

摘要: The infrequent association of serous borderline tumors (SBTs) with invasive carcinoma has led to the view that SBTs are unrelated carcinoma. Nonetheless, mortality associated is generally attributed malignant transformation, and traditionally these have been designated as "carcinomas low potential." Previous immunohistochemical studies evaluating p53 expression molecular genetic mutational status reported overexpression mutations in occur many 50% 80% carcinomas. different methodologies for determining failure correlate findings tumor grade make difficult interpret. current study was undertaken overcome deficiencies reconcile relationship by performing a morphologic, immunohistochemical, analysis comparing low- high-grade used highly stringent, carefully designed nucleotide-sequencing method. A total 96 sporadic including 25 (11 atypical proliferative 14 intraepithelial low-grade carcinomas [noninvasive micropapillary carcinomas, MPSCs]), 12 (invasive MPSCs), 59 were analyzed their exons 5 9. Functional mutations, defined resulting alteration structure encoded protein, detected 30 (50.8%) 1 (8.3%) compared 2 (8%) SBTs, both (noninvasive MPSCs). similar frequency contrast significantly higher (P < 0.0005) suggests common lineage supports usual type carcinoma, which neoplasm. Mutational also correlated immunoreactivity. Although immunoreactivity those specimens containing mutant p53, immunostaining neither sufficiently specific nor sensitive enough predict mutations. confirm our hypothesis dual pathways carcinogenesis based on previous analyses KRAS BRAF same set cases found 60% but not Based studies, we proposed model precursors whereas neoplasm develops "de novo" from situ alterations epithelial inclusion cysts.