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Prognostic assessment of sarcomatous histologic subtypes of ovarian carcinosarcoma.

ABSTRACT: Ovarian carcinosarcoma is a rare subtype of this disease that has not been thoroughly investigated. The aim of this study was to evaluate the prognostic factors and out comes in patients with ovarian carcinosarcoma.All patients with histologically confirmed ovarian carcinosarcoma who were treated at Cheil General Hospital and Women's Healthcare Center between January 2000 and December 2015 were identified and analyzed. Data were extracted from medical records, and statistical analyses were performed to determine correlations between clinicopathological parameters and survival outcomes.Of the 822 patients diagnosed with ovarian cancer over 16 years, 11 (1.3%) had ovarian carcinosarcoma histology. Every patient underwent surgery as the initial treatment followed by intravenous adjuvant chemotherapy. Only 18.1% of cases were early stage (I or II) while 81.8% were advanced stage (III or IV) according to the FIGO (International Federation of Gynecology and Obstetrics) classification. Six cases were of the homologous subtype (54.5%) and five were of the heterologous subtype (45.5%). There was no significant difference in survival according to stage (P=0.24). The heterologous subtype and residual disease were associated with poor disease-free survival (P=0.02 and P=0.04) and overall survival (P=0.02 and P=0.04), On multivariate analysis, the histological subtype was an independent prognostic factor (P=0.02).Optimal cytoreduction without gross residual disease and a homologous subtype are favorable prognostic factors in terms of disease relapse and survival.

SUBMITTER: Kim HJ

PROVIDER: S-EPMC5547082 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Prognostic factors and clinic-pathologic characteristics of ovarian tumor with different histologic subtypes-a SEER database population study of 41,376 cases.

Project description:BackgroundOvarian cancer is considered the leading cause of cancer-related deaths among all gynecological malignancies and a significant reason for mortality in women. This cohort study aimed to explore the survival trends of malignant ovarian tumors (MOT), cancer antigen 125 (CA125) level, and clinicopathological prognostic factors of MOT by histological subtype.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, a total of 41,411 MOT cases diagnosed between January 2005 and December 2014 were extracted. According to the histological classification of MOT, four categories were included: epithelial ovarian carcinoma (EOC), malignant ovarian germ cell tumors (MOGCTs), malignant ovarian sex cord-stromal tumors (MOSCSTs) and ovarian neuroendocrine tumors (ONTs). We analyzed disease-specific survival (DS) and overall survival (OS) among the four categories, and their histological subtypes. Kaplan-Meier method was used to estimate survival curves, and log-rank test was used to evaluate differences between curves. Univariate and multivariate Cox proportional hazards models were applied to evaluate the prognostic impact of MOT.ResultsSignificant predictors related to improved OS were younger age, low grade, early FIGO stage and localized SEER stage, while positive/elevated CA125 level was a risk factor. For MOGCT and MOSCST, 3-, 5- and 10-year DS rate estimates were all >80%, followed by ONT around 70%. Malignant epithelial cancer showed low DS rate at 3-year (70.7%), 5-year (58.7%), and 10-year (47.3%).ConclusionsEOC patients had the worst outcome, whereas MOGCT cases had the most favorable survival. Positive/elevated CA125 level led to poor prognosis. Furthermore, younger age, low grade, early FIGO stage and localized SEER stage were significant predictors for improved OS.

| S-EPMC10493794 | biostudies-literature

Characterization of fusion genes in common and rare epithelial ovarian cancer histologic subtypes.

Project description:Gene fusions play a critical role in some cancers and can serve as important clinical targets. In epithelial ovarian cancer (EOC), the contribution of fusions, especially by histological type, is unclear. We therefore screened for recurrent fusions in a histologically diverse panel of 220 EOCs using RNA sequencing. The Pipeline for RNA-Sequencing Data Analysis (PRADA) was used to identify fusions and allow for comparison with The Cancer Genome Atlas (TCGA) tumors. Associations between fusions and clinical prognosis were evaluated using Cox proportional hazards regression models. Nine recurrent fusions, defined as occurring in two or more tumors, were observed. CRHR1-KANSL1 was the most frequently identified fusion, identified in 6 tumors (2.7% of all tumors). This fusion was not associated with survival; other recurrent fusions were too rare to warrant survival analyses. One recurrent in-frame fusion, UBAP1-TGM7, was unique to clear cell (CC) EOC tumors (in 10%, or 2 of 20 CC tumors). We found some evidence that CC tumors harbor more fusions on average than any other EOC histological type, including high-grade serous (HGS) tumors. CC tumors harbored a mean of 7.4 fusions (standard deviation [sd] = 7.4, N = 20), compared to HGS EOC tumors mean of 2.0 fusions (sd = 3.3, N = 141). Few fusion genes were detected in endometrioid tumors (mean = 0.24, sd = 0.74, N = 55) or mucinous tumors (mean = 0.25, sd = 0.5, N = 4) tumors. To conclude, we identify one fusion at 10% frequency in the CC EOC subtype, but find little evidence for common (> 5% frequency) recurrent fusion genes in EOC overall, or in HGS subtype-specific EOC tumors.

| S-EPMC5564530 | biostudies-literature

Pediatric Differentiated Thyroid Carcinoma of Follicular Cell Origin: Prognostic Significance of Histologic Subtypes.

Project description:BackgroundThyroid cancers are rare in the pediatric age group, and unlike in adults, few data are available regarding the clinical implication of histologic subtypes in the pediatric population. The purpose of the current study was to determine the prognostic significance of histologic subtypes of differentiated thyroid cancer (DTC) in a large series of children and adolescents followed at a single institution.MethodsA retrospective review was conducted of all pediatric DTC patients who were treated and followed between 1988 and 2012. Sixty-two patients (median age at diagnosis 13.8 years, median age at follow-up 18 years, 77% female) were assessed. The most common subtypes included classic papillary thyroid carcinoma (PTC; 48%), diffuse sclerosing PTC (16%), and follicular variant PTC (15%); 37% were considered "high-risk" histologies based on adult criteria.ResultsIn a multivariate model, only extensive extrathyroidal extension (ETE), defined as the presence of two or more microscopic foci of tumor cells ≤1 mm in size each or any foci >1 mm in size invading beyond the thyroid capsule into perithyroid soft tissue or organs, was significantly associated with extent of disease at presentation. At last follow-up, 76% of subjects had no evidence of disease, 18% had persistent disease, and 5% had recurrent/progressive disease. Event-free survival was associated with extent of disease at presentation (p = 0.01), extensive ETE at diagnosis (p < 0.01), and male sex (p = 0.01), but not histologic subtype (p = 0.20).ConclusionsPediatric DTC carries an excellent prognosis. Extensive ETE at diagnosis was found to be an independent predictor of extent of disease at presentation, as well as event-free survival. Unlike in the adult population, "high-risk" histologic subtypes did not independently predict extent of disease at presentation or event-free survival in this pediatric population with DTC.

| S-EPMC4855728 | biostudies-literature

Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort.

Project description:Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (phet ?=?0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; phet ?=?0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.

| S-EPMC6284794 | biostudies-literature

SPME-LC/MS-based serum metabolomic phenotyping for distinguishing ovarian cancer histologic subtypes: a pilot study.

Project description:Epithelial ovarian cancer (EOC) is the most common cause of death from gynecological cancer. The outcomes of EOC are complicated, as it is often diagnosed late and comprises several heterogenous subtypes. As such, upfront treatment can be highly challenging. Although many significant advances in EOC management have been made over the past several decades, further work must be done to develop early detection tools capable of distinguishing between the various EOC subtypes. In this paper, we present a sophisticated analytical pipeline based on solid-phase microextraction (SPME) and three orthogonal LC/MS acquisition modes that facilitates the comprehensive mapping of a wide range of analytes in serum samples from patients with EOC. PLS-DA multivariate analysis of the metabolomic data was able to provide clear discrimination between all four main EOC subtypes: serous, endometrioid, clear cell, and mucinous carcinomas. The prognostic performance of discriminative metabolites and lipids was confirmed via multivariate receiver operating characteristic (ROC) analysis (AUC value > 88% with 20 features). Further pathway analysis using the top 57 dysregulated metabolic features showed distinct differences in amino acid, lipid, and steroids metabolism among the four EOC subtypes. Thus, metabolomic profiling can serve as a powerful tool for complementing histology in classifying EOC subtypes.

| S-EPMC8599860 | biostudies-literature

Prognostic significance of stem cell-related marker expression and its correlation with histologic subtypes in lung adenocarcinoma.

Project description:Cancer stem cells (CSCs) are a small subset of tumor cells that exhibit stem cell-like properties and contribute in treatment failure. To clarify the expression and prognostic significance of several CSC markers in non-small cell lung cancer, we retrospectively analyzed 368 patients with adenocarcinoma (n = 226) or squamous cell carcinoma (n = 142). We correlated the expression of six CSC markers - CD133, CD44, aldehyde dehydrogenase 1 (ALDH1), sex determining region Y-box 2 (SOX2), octamer binding transcription factor 4 (OCT4), and Nanog - with clinicopathologic and molecular variables and survival outcomes. In adenocarcinoma, CD133, ALDH1 and CD44 expression was associated with low pathologic stage and absence of lymphovascular invasion, while Nanog expression correlated with high histologic grade, lymphatic invasion and increased expression of Snail-1, a transcription factor associated with epithelial-mesenchymal transition. CSC marker expression was also associated with histologic subtypes in adenocarcinoma. Multivariate analysis showed that high Nanog expression was an independent factor associated with a poor prognosis in adenocarcinoma. CSC markers had no prognostic value in squamous cell carcinoma. These results suggest that Nanog is an independent negative prognostic factor that may be associated with epithelial-mesenchymal transition in lung adenocarcinoma.

| S-EPMC5173151 | biostudies-literature

Comprehensive assessment of the expression of the SWI/SNF complex defines two distinct prognostic subtypes of ovarian clear cell carcinoma.

Project description:Somatic mutations in the ARID1A tumor-suppressor gene have been frequently identified in ovarian clear cell carcinoma (CCC) cases. BAF250a encoded by ARID1A is a member of the SWI/SNF complex, but the expression and mutation status of other SWI/SNF subunits have not been explored. The current study aimed to elucidate the biological and clinical significance of the SWI/SNF complex subunits, by assessing the expression and mutation status of SWI/SNF subunits, and distinct genomic aberrations associated with their expression. Of 82 CCC specimens, 38 samples presented no BAF250a expression, and 50 samples exhibited the loss of at least one subunit of the SWI/SNF complex. Cases which lack at least one SWI/SNF complex component exhibited significantly more advanced stages, faster growth and stronger nuclear atypia compared with SWI/SNF-positive samples (p<0.05). Although BAF250a expression is not related to poor prognosis, the group presenting the loss of at least one SWI/SNF complex subunit exhibited significantly shorter overall and progression-free survivals (p<0.05). A multivariate analysis suggested that the expression status of the SWI/SNF complex serves as an independent prognostic factor (p<0.005). The cases positive for all SWI/SNF subunits demonstrated significantly greater DNA copy number alterations, such as amplification at chromosomes 8q.24.3 and 20q.13.2-20q.13.33 (including ZNF217) and deletion at chromosomes 13q12.11-13q14.3 (including RB1), 17p13.2-17p13.1 (including TP53) and 19p13.2-19p13.12. In conclusion, the CCCs exhibiting the loss of one or multiple SWI/SNF complex subunits demonstrated aggressive behaviors and poor prognosis, whereas the CCCs with positive expression for all SWI/SNF components presented more copy number alterations and a favorable prognosis.

| S-EPMC5342379 | biostudies-literature

Comparing molecular assessment of implantation biopsies with histologic and demographic risk assessment.

Project description:In deceased donor kidney transplantation, acute kidney injury (AKI) prioir to surgery is a major determinant of delayed graft function (DGF), but AKI is histologically silent and difficult to assess. We hypothesized that a molecular measurement of AKI would add power to conventional risk assessments to predict the early poor allograft function at first week post transplantation.

2013-02-13 | GSE37838 | GEO

Breast cancer histologic subtypes show excess familial clustering.

Project description:BACKGROUND:The inherited predisposition to developing specific histologic subtypes of invasive breast carcinoma has been incompletely investigated. By using a large, population-based database, the authors sought to investigate familial clustering of breast cancer by histologic subtype. METHODS:By using the Utah Population Database, which links genealogy records to the National Cancer Institute's statewide Surveillance, Epidemiology, and End Results cancer registry, the authors identified patients with breast cancer by histology and tested for evidence of shared genetic predisposition to histologic specific subtypes by examining pairwise relatedness and estimating the relative risk (RR) among first-degree, second-degree, and third-degree relatives. RESULTS:The authors identified 23,629 individuals in the Utah Population Database who had at least 3 generations of genealogy and at least 1 primary breast cancer, 2883 (12.2%) of which were specific histologic subtypes other than invasive ductal carcinoma (including inflammatory [n = 178], lobular [n = 1688], and mucinous [n = 542]). Statistically significant excess distant relatedness was identified for the mucinous subtype (P = .011) as well as for inflammatory breast cancers (P = .024). The RR for breast cancer of any histology in second-degree relatives was significantly increased for patients with inflammatory (RR, 1.32; 95% CI, 1.02-1.68; P = .03), lobular (RR, 1.36; 95% CI, 1.25-1.47; P < .001), and mucinous (RR, 1.27; 95% CI, 1.12-1.44; P = .00021) subtypes. CONCLUSIONS:These findings provide evidence for significant familial clustering within histological subtypes for lobular, mucinous, and inflammatory breast carcinomas. Further research is required to identify the underlying genetic variants responsible for the increased risk. Studies of high-risk pedigrees segregating a specific histologic subtype could be a powerful design for predisposition gene identification.

| S-EPMC6716995 | biostudies-literature

Prognostic and therapeutic relevance of molecular subtypes in high-grade serous ovarian cancer.

Project description:Molecular classification of high-grade serous ovarian cancer (HGSOC) using transcriptional profiling has proven to be complex and difficult to validate across studies. We determined gene expression profiles of 174 well-annotated HGSOCs and demonstrate prognostic significance of the prespecified TCGA Network gene signatures. Furthermore, we confirm the presence of four HGSOC transcriptional subtypes using a de novo classification. Survival differed statistically significantly between de novo subtypes (log rank, P = .006) and was the best for the immunoreactive-like subtype, but statistically significantly worse for the proliferative- or mesenchymal-like subtypes (adjusted hazard ratio = 1.89, 95% confidence interval = 1.18 to 3.02, P = .008, and adjusted hazard ratio = 2.45, 95% confidence interval = 1.43 to 4.18, P = .001, respectively). More prognostic information was provided by the de novo than the TCGA classification (Likelihood Ratio tests, P = .003 and P = .04, respectively). All statistical tests were two-sided. These findings were replicated in an external data set of 185 HGSOCs and confirm the presence of four prognostically relevant molecular subtypes that have the potential to guide therapy decisions.

| S-EPMC4271115 | biostudies-literature

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