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BACKGROUND: Borderline ovarian tumors (BTs) must be recognized during the surgery by intraoperative consultation (IOC) to guide surgical treatment; however, this diagnosis can be imprecise. Therefore, this study aimed to evaluate the diagnostic accuracy of IOC for the diagnosis of BT. METHODS: A retrospective cohort study was carried out including all women diagnosed with a pelvic tumor consecutively surgically treated from 2005 to 2015 with IOC. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LR) for the IOC and BTs. RESULTS: A total of 758 patients were enrolled, the median age was 44 years, the median tumor size was 11.8 cm, and the median CA-125 levels were 45.65 U/µL. After IOC, 458 (64.1%) cases were diagnosed as benign, 111 (14.7%) as BT, and 161 (21.2%) as malignant. The definitive diagnosis was a benign tumor in 448 (59.1%) cases, BT in 110 (14.5%), and 200 (26.4%) cases were malignant. The diagnostic accuracy of the IOC for BT diagnosis was 89.8% (sensitivity =65.5%, specificity =93.9%). The diagnosis performance of IOC for the diagnosis between BT and benign tumors (n=546) had a sensitivity of 69.9%, a specificity of 98.4%, and a diagnostic accuracy of 84%; meanwhile for the diagnosis between BT and malignant tumors (n=242) IOC had a sensitivity of 92.3%, a specificity of 81.7%, and a diagnostic accuracy of 87%. CONCLUSIONS: For practitioners, knowing the accuracy and limitations of the IOC for BT enables the better selection of cases to perform a complete staging surgery.
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Liquid-based cytology (LBC) has been used as a diagnostic tool for cervical cancer for years and is now being adopted for other gynecological cancers. LBC represents an important challenge to ensure that the process yields representative biospecimens for quality control (QC) of diagnostic procedures. In this study, we compare QC parameters (integrity, yield and purity, and polymerase chain reaction [PCR] amplification) of DNA isolated from LBC (N = 296) using two different nucleic acid isolation methods, manual (n = 233) or automated (n = 63). We also evaluated two different types of cytological brushes for sampling from the cervix. Our results suggest that manual isolation (yield 22.81 ± 1.92 µg) resulted in increased DNA recovery when compared with automated isolation (yield 9.96 ± 1.11 µg) from LBC samples, with a p-value of <0.0003. We estimated that 98% (53/54) of the samples preserved the integrity of DNA and were suitable for standard molecular biology analyses. The ß-globin gene was amplified in 100% (296/296) of the DNA samples by endpoint PCR. We found no significant difference between the performance of the cytological brushes (p value of <0.6711) in a general overview. However, when looking at the results from using each brush individually, the manual isolation method was statistically superior to the automated method. Our work illustrates the impact of good QC of preanalytic conditions, which will be important for the application of LBC for developing early detection methods for gynecological cancers.
Assuntos
DNA de Neoplasias/isolamento & purificação , Manejo de Espécimes/métodos , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bancos de Espécimes Biológicos , Detecção Precoce de Câncer , Feminino , Humanos , Biópsia Líquida , Neoplasias do Colo do Útero/genética , Adulto JovemRESUMO
BACKGROUND: Heterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients. METHODS: We searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control. RESULTS: We identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53. CONCLUSIONS: Among Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.