PTEN Loss Expands the Histopathologic Diversity and Lineage Plasticity of Lung Cancers Initiated by Rb1/Trp53 Deletion.

INTRODUCTION: High-grade neuroendocrine tumors of the lung such as SCLC are recalcitrant cancers for which more effective systemic therapies are needed. Despite their histopathologic and molecular heterogeneity, they are generally treated as a single disease entity with similar chemotherapy regimens. Whereas marked clinical responses can be observed, they are short-lived. Inter- and intratumoral heterogeneity is considered a confounding factor in these unsatisfactory clinical outcomes, yet the origin of this heterogeneity and its impact on therapeutic responses is not well understood. METHODS: New genetically engineered mouse models are used to test the effects of PTEN loss on the development of lung tumors initiated by Rb1 and Trp53 tumor suppressor gene deletion. RESULTS: Complete PTEN loss drives more rapid tumor development with a greater diversity of tumor histopathology ranging from adenocarcinoma to SCLC. PTEN loss also drives transcriptional heterogeneity as marked lineage plasticity is observed within histopathologic subtypes. Spatial profiling indicates transcriptional heterogeneity exists both within and among tumor foci with transcriptional patterns correlating with spatial position, implying that the growth environment influences gene expression. CONCLUSIONS: These results identify PTEN loss as a clinically relevant genetic alteration driving the molecular and histopathologic heterogeneity of neuroendocrine lung tumors initiated by Rb1/Trp53 mutations.

Prevalence and incidence of pseudomyxoma peritonei in urban China: A nationwide retrospective cohort study.

BACKGROUND: Pseudomyxoma peritonei (PMP) is an extremely rare condition. Information regarding the disease burden of PMP in developing countries is limited. This study aimed to determine the epidemiology of PMP in China. METHODS: PMP data were extracted from the national databases of Urban Basic Medical Insurance. All cases were identified using the International Classification of Diseases (ICD) codes and Chinese diagnostic terms. The national prevalence from 2012 to 2016 and incidence in 2016 were estimated. RESULTS: In total, 153 patients with PMP were identified. The crude prevalence of PMP in 2016 was 2.47 (95% confidence interval [CI] 1.71 to 3.23) per million person-year, with a higher prevalence in females than males. Prevalence increased with age, with the first peak in those aged 15-29 years and the highest in those aged >80 years. The crude incidence of PMP in 2016 was 1.19 (95% CI 0.59 to 1.78) per million person-years. Similar to the prevalence, the rates were higher in women than in men. The incidence also increased with age, with the highest prevalence in those aged >80 years. Besides, the most frequent comorbidities before and after the first diagnosis of PMP were unspecified secondary malignancies and malignancies of unspecified sites, followed by abdominal malignant tumours. CONCLUSIONS: The rate of PMP was lower in mainland China than in European countries and increased with advancing age. Women were more likely to have PMP than men. Furthermore, an insufficient understanding of this rare disease presents a major challenge in accurately evaluating the disease burden.

Kinetochore-associated protein 1 promotes the invasion and tumorigenicity of cervical cancer cells via matrix metalloproteinase-2 and matrix metalloproteinase-9.

Cervical cancer, a common cancer in women, has become a serious social burden. Kinetochore-associated protein 1 (KNTC1) that regulates the cell cycle by regulating mitosis is related to the malignant behavior of different types of tumors. However, its role in the development of cervical cancer remains unclear. In this study, we initially explored the role of KNTC1 in cervical cancer. KNTC1 expression and relevant information were downloaded from The Cancer Genome Atlas (TCGA) and dataset GSE63514 in the Gene Expression Omnibus (GEO) database for bioinformatics analyses. Cell proliferation was detected by cell counting kit-8 (CCK8) and colony formation assays. Wound healing and Transwell assays were used to evaluate cell migration and invasion abilities. Protein expression levels of matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9) were measured by western blotting. Nude mouse models of subcutaneous xenograft tumor were constructed to analyze tumor growth in vivo. CCK8 and colony formation assay results demonstrated that the proliferation rate of SiHa and C-33A cells decreased when KNTC1 was silenced. Western blot and Transwell assays indicated that KNTC1 knockdown weakened the invasion and migration abilities of SiHa and C-33A cells and decreased the expression of MMP-2 and MMP-9. In-vivo experiments suggested that the inhibition of KNTC1 reduced tumor growth. Taken together, our study showed that KNTC1 plays an important role in cervical cancer. Further, we verified the promotional effect of KNTC1 on cervical cancer through in-vivo and in-vitro experiments and speculated that KNTC1 might mediate tumor invasion via MMP9 and MMP2.

Case Report: An Unusual First Manifestation of a Pheochromocytoma.

We present a 30-year old male presented with hemoptysis as a first manifestation and pulmonary CT scan characteristic of diffuse alveolar hemorrhage. Further abdominal examination discovered a left adrenal mass. Elevated catecholamine and metanephrine levels and subsequent adrenalectomy confirmed the diagnosis of pheochromocytoma. Symptoms of pheochromocytoma are highly variable, which could potentially delay the diagnosis. With careful investigation, emergency medicine practitioners need to be aware of the cunning and changeful manifestations in pheochromocytoma.

Abnormal Elevation of Anti-Mullerian Hormone and Androgen Levels Presenting as Granulosa Cell Tumor.

We report a rare subtype of adult cystic granulosa cell tumor (AGCT) characterized by elevated anti-Mullerian hormone and hyperandrogenism. A 35-year-old woman with primary infertility, hyperandrogenism, and irregular menses who was previously diagnosed with polycystic ovarian syndrome was diagnosed with AGCT based on histopathological examination and FOXL2 genetic test after laparoscopy. Due to fertility aspirations, she underwent controlled ovarian stimulation followed by embryo cryopreservation before salpingo-oophorectomy, and two embryos were frozen-thawed and transferred after surgery. A healthy female infant was delivered at 40 weeks' gestation. Cystic granulosa cell tumors should be considered a differential diagnosis in patients with persistent ovarian cysts and hyperandrogenism. Younger patients with AGCT with fertility goals should consider active assisted reproduction measures to preserve fertility before treatment for AGCT.

[Advances in research on the development of female germ cells].

The development of female germ cells can be mainly divided into two stages: fetal germ cells and oocytes in folliculogenesis after puberty. Mitosis-meiosis transition, meiosis arrest and re-activation are the key phases of the development. Several phases may be characterized by their distinct molecular events, which involve precise regulation of gene expression and interaction with corresponding gonadal niche cells. In recent years, single-cell transcriptome studies have clarified phase-specific patterns of gene expression, signaling pathways and epigenetic modification during oogenesis and folliculogenesis. These works have provided important insights into the development of female germ cells and pathogenesis of germ-cell related diseases, which may promote clinical application of reproductive genetic research.

Sodium iodide-mediated synthesis of vinyl sulfides and vinyl sulfones with solvent-controlled chemical selectivity.

Vinyl sulfides and vinyl sulfones are ubiquitous structures in organic chemistry because of their presence in natural and biologically active compounds and are very frequently encountered structural motifs in organic synthesis. Herein we report an efficient synthesis of vinyl sulfides and vinyl sulfones via transition metal-free sodium iodide-mediated sulfenylation of alcohols and sulfinic acids with solvent-controlled selectivity.

Clinicopathological significance of multiple molecular features in undifferentiated and dedifferentiated endometrial carcinomas.

We investigated the clinicopathological significance of multiple molecular features in undifferentiated and dedifferentiated endometrial carcinomas (UDECs). Eighteen dedifferentiated endometrial carcinomas (DDECs) and three undifferentiated endometrial carcinomas (UECs) were collected. Polymerase-ε exonuclease domain mutations (POLE-EDM) were analysed by Sanger sequencing. SWI/SNF complex subunits, mismatch repair (MMR) proteins, p53, and PD-L1 were evaluated by immunohistochemistry. The SWI/SNF complex was inactivated in half of the UDECs; variably combined with deficient MMR (dMMR), POLE-EDM, or p53 aberrance. Deficiencies in BRG1 and ARID1A were mutually exclusive (p<0.05) in DDECs. ARID1A defects were mostly (8/9) associated with dMMR and typically occurred simultaneously in both endometrioid and dedifferentiated components, whereas BRG1 defects were less frequently (3/7) combined with dMMR and were only observed in dedifferentiated cells. Two-thirds of the UDECs displayed dMMR, mainly caused by the MLH1 promotor methylation. Mutant p53 immunostaining was detected in accordant or subclonal patterns. All three POLE-EDM UDEC patients had stage IA disease with either dMMR or p53 abnormality. Strong positive signals for PD-L1 were mainly detected in dMMR samples. BRG1 defects may likely trigger the progression of dedifferentiation in UDECs by superimposing the pre-existing driver events or by initiating UECs de novo, whereas ARID1A inactivation is subordinate and may likely be secondary to dMMR. The biological behaviours of BRG1-intact UDECs were evaluated according to The Cancer Genome Atlas molecular classification; their driver events require further analysis. Exact molecular subtypes can be helpful for clinical management and treatment decisions for patients with UDEC.

Loss of 4.1N in epithelial ovarian cancer results in EMT and matrix-detached cell death resistance.

Epithelial ovarian cancer (EOC) is one of the leading causes of death from gynecologic cancers and peritoneal dissemination is the major cause of death in patients with EOC. Although the loss of 4.1N is associated with increased risk of malignancy, its association with EOC remains unclear. To explore the underlying mechanism of the loss of 4.1N in constitutive activation of epithelial-mesenchymal transition (EMT) and matrix-detached cell death resistance, we investigated samples from 268 formalin-fixed EOC tissues and performed various in vitro and in vivo assays. We report that the loss of 4.1N correlated with progress in clinical stage, as well as poor survival in EOC patients. The loss of 4.1N induces EMT in adherent EOC cells and its expression inhibits anoikis resistance and EMT by directly binding and accelerating the degradation of 14-3-3 in suspension EOC cells. Furthermore, the loss of 4.1N could increase the rate of entosis, which aggravates cell death resistance in suspension EOC cells. Moreover, xenograft tumors in nude mice also show that the loss of 4.1N can aggravate peritoneal dissemination of EOC cells. Single-agent and combination therapy with a ROCK inhibitor and a 14-3-3 antagonist can reduce tumor spread to varying degrees. Our results not only define the vital role of 4.1N loss in inducing EMT, anoikis resistance, and entosis-induced cell death resistance in EOC, but also suggest that individual or combined application of 4.1N, 14-3-3 antagonists, and entosis inhibitors may be a promising therapeutic approach for the treatment of EOC.

A Retrospective Study and Literature Review of Cervical Villoglandular Adenocarcinoma: A Candidate Paradigm of Silva System Pattern A.

The aim was to investigate the clinicopathologic characters of cervical villoglandular adenocarcinoma (VGA), the authors retrospectively reviewed 4 cases of VGA, including clinical characteristics, pathology, managements, together with outcome information. The median age of the patients was 42 (range: 37 to 58), with 3 of them presenting with stage IB disease and 1 presenting with IVB. Human papillomavirus infection was tested in 3 of the patients, with all positive with high-risk type. Three of the patients underwent a radical hysterectomy with bilateral salpingo-oophorectomy plus bilateral pelvic lymphadenectomy, and 2 of them underwent subsequent chemotherapy. One patient received a bilateral salpingo-oophorectomy plus pelvic and periaortic lymphadenectomy and postoperative radiochemotherapy. Lymph node metastasis was detected in 1 patient. The follow-up time ranged from 56 to 120 months (median: 70 mo). Except for 1 person who experienced recurrence, all patients are alive at present and no recurrence occurred. In conclusion, VGA is a rare subtype of adenocarcinoma of the uterine cervix with distinct exophytic, villous-papillary growth pattern and extremely excellent prognosis, which corresponds with pattern A in Silva system, while its underlying mechanism and genetic background is still far from well known.

Au-Catalyzed intermolecular (3 + 2 + 1) and (5 + 2) cycloaddition for the synthesis of 1,4-dioxenes and 4,7-dihydrooxepines.

1,4-Dioxenes and 4,7-dihydrooxepines present interesting potential as motifs for the incorporation of biologically relevant molecules, agrochemicals and materials. In this study, two efficient intermolecular (3 + 2 + 1) and (5 + 2) cycloadditions for the synthesis of 1,4-dioxenes and 4,7-dihydrooxepines are achieved with gold catalysis.

Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancer.

Objective: Lynch syndrome (LS) predisposes patients to early onset endometrioid endometrial cancer (EEC). However, little is known about LS-related EEC in the Chinese population. The aim of this study was to investigate the prevalence of LS and to identify the specific variants of LS in Chinese patients with EEC. Methods: We applied universal immunohistochemistry screening to detect the expression of mismatch repair (MMR) proteins, which was followed by MLH1 methylation analysis to identify suspected LS cases, next-generation sequencing (NGS) to confirm LS, and microsatellite instability (MSI) analysis to verify LS. Results: We collected 211 samples with EEC. Twenty-seven (27/211, 12.8%) EEC cases had a loss of MMR protein expression. After MLH1 methylation analysis, 16 EEC cases were suggested to be associated with LS. Finally, through NGS and MSI analysis, we determined that 10 EEC (10/209, 4.78%) cases were associated with LS. Among those cases, 3 unreported mutations (1 frameshift and 2 nonsense) were identified. MSH6 c.597_597delC, found in 4 patients, is likely to be a founder mutation in China. Conclusions: We demonstrated the feasibility of a process for LS screening in Chinese patients with EEC, by using universal immunohistochemistry screening followed by MLH1 methylation analysis and confirmation through NGS and MSI analysis. The novel mutations identified in this study expand knowledge of LS.

Identification of a hydatidiform mole in twin pregnancy following assisted reproduction.

PURPOSE: The aim of this study was to identify a co-existing hydatidiform mole (HM) in twin pregnancy from the abnormal mixed-genomic products of conception (POC) after assisted reproduction by histopathological review, evaluation of p57kip2 immunostaining and short tandem repeat genotyping. METHODS: Thirty-seven patients were collected with suspicion for HM by pathological morphology. They had two embryos individually transferred to their uterus after in vitro fertilization and presented two gestational sacs with undeveloped embryos or one sac with an abnormal area by ultrasonography. RESULTS: Thirty patients were diagnosed as singleton pregnancy, including twenty-two non-molar gestations, six trisomy gestations, one homozygous complete mole and one heterozygous partial mole. Although six patients had ultrasonic imaging of two gestational sacs, the embryonic components in the vacant sac might fade away after transferring. Other seven patients were considered as twin pregnancy by the allelic genotype from two individual conceptions. For the patients with uniform p57kip2 positivity, excessive paternal alleles indicated the potential partial HM in the twin pregnancy. For the patients demonstrated divergent and/or discordant p57kip2 immunostaining, twin pregnancy with co-existing complete HM or mosaic conception were confirmed by genotyping of different villi population respectively. These patients were monitored by serum ß-HCG, while one twin pregnancy with complete mole suffered invasive mole and received chemotherapy. CONCLUSIONS: A strategy composed of selective clinicopathological screening, immunohistochemical interpretation and accurate genotyping is recommended for diagnostically challenging mixed-genomic POC of potential twin pregnancy with HM, especially to differentiate a non-molar mosaic conception from a partial mole.

Au-Catalyzed tandem intermolecular hydroalkoxylation/Claisen rearrangement between allylic alcohols and chloroalkynes.

An efficient protocol for the synthesis of γ,δ-unsaturated α-chloroketones has been developed via Au-catalyzed tandem intermolecular hydroalkoxylation/Claisen rearrangement. In the presence of 1 mol% JohnPhosAuCl and 1 mol% NaBArF, a broad range of allylic alcohols smoothly underwent the tandem intermolecular hydroalkoxylation/Claisen rearrangement with aromatic, vinylic or aliphatic chloroalkynes to give structurally diverse γ,δ-unsaturated α-chloroketones in excellent yields. Importantly, high Z/E selectivity was achieved. Other advantages are widespread availability of the substrates, compatibility with a broad range of functional groups and mild reaction conditions.

Comparison of Different Scoring Systems in the Assessment of Estrogen Receptor Status for Predicting Prognosis in Endometrial Cancer.

The objective of this article is to compare the effectiveness of various estrogen receptor (ER) scoring systems for predicting prognosis in endometrial cancer (EC). We retrospectively analyzed 195 cases of primary EC with complete follow-up information. Three different methods-the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criterion, histochemistry score (H-score), and Allred scoring system-were used to assess the degree of staining, and comparisons were made to determine which method correlated best with clinical outcomes. The ASCO/CAP criterion, H-score (cutoff value, 51-300), and Allred (cutoff value, 4-8) scoring systems showed high concordance in the following aspects: the ER status was significantly associated with subtype (type I vs. type II EC), newly recommended histologic type (grade 1-2, type I vs. grade 3, type I+type II EC), progesterone receptor status, overall survival, and cancer-specific survival in EC patients. Considering International Federation of Gynecology and Obstetrics stage, lymphovascular space invasion, and lymph node metastasis, the ASCO/CAP criterion significantly exceeded the other 2 scoring systems. Furthermore, cases judged as ER positive by the ASCO/CAP criterion, but ER negative by the other 2 scoring systems, displayed similarly favorable outcomes to those cases that were consistently admitted as ER positive by all 3 scoring systems. The ASCO/CAP criterion was superior to both H-score and Allred score in terms of predictive and prognostic values. This easy, simple, and highly efficient criterion should be recommended for routine assessment of ER in EC patients.

Apparent Diffusion Coefficient Histogram Analysis for Assessing Tumor Staging and Detection of Lymph Node Metastasis in Epithelial Ovarian Cancer: Correlation with p53 and Ki-67 Expression.

PURPOSE: To investigate the potential of apparent diffusion coefficient (ADC) histogram parameters in epithelial ovarian cancer (EOC) for distinguishing different tumor stages and determining lymph node status and correlations between ADC values and p53 and Ki-67 expression. PROCEDURES: Forty-nine EOC patients underwent preoperative magnetic resonance imaging. Staging and lymph node status were determined postoperatively. ADC values were measured using histogram analysis and compared between groups. Relationships between ADCs and Ki-67 and p53 expression were explored. RESULTS: DC parameters differed significantly between stage I vs II, I vs III, and I vs IV. The parameters were significantly lower in the lymph node-positive group than in the lymph node-negative group, were significantly negatively correlated with Ki-67 labeling index, and were all significantly lower in the mutation-type p53 group than in the wild-type p53 group. CONCLUSIONS: ADC histogram analysis can help discriminate stage I from advanced-stage EOC and predict lymph node metastasis. ADC parameters were correlated with Ki-67 labeling index; the parameters may help indicate p53 expression.

Study of the revisited, revised, and expanded Silva pattern system for Chinese endocervical adenocarcinoma patients.

As a new pattern-based classification, the Silva pattern system has been recently developed to evaluate invasive lymph node metastasis and the prognosis of endocervical adenocarcinoma (EAC). Therefore, our study was conducted to explore the reproducibility and prognostic significance of this system in a multi-institutional Chinese cohort, with the goal of revising and expanding its application. The clinicopathological data of 191 EAC patients from 3 medical centers were examined in a retrospective manner. The Silva pattern system demonstrated great prognostic value, significance in guiding treatment selection, and acceptable reproducibility in 191 patients that included additional histologic variants and 124 usual-type EAC patients. Collectively, compared with usual-type EAC, the whole cohort demonstrated similar statistical significance for relevant clinicopathological parameters, such as International Federation of Gynecology and Obstetrics stage (R = 0.612 versus R = 0.600), tumor thickness (P < .0001 versus P < .0001), lymphovascular invasion (P < .0001 versus P < .0001), lymph node metastasis (P = .033 versus P = .018), perineural invasion (P = .003 versus P = .001), and recurrence-free survival (P = .047 versus P = .020). Moreover, perineural invasion was significantly correlated (P = .001) with the Silva pattern system and appeared in most Silva C tumors. In conclusion, the Silva pattern system is consistent with the biological behavior of EAC and has acceptable reproducibility. Compared with International Federation of Gynecology and Obstetrics stage, it can predict patient prognosis before surgery. We suggest revising the Silva C criteria by adding perineural invasion as a factor and propose expanding the Silva pattern system to include more histologic variants. It seems that the Silva pattern system can be applied in routine clinical practice to guide EAC therapeutic strategies in the near future.

Analysis of Circulating Tumor Cells in Ovarian Cancer and Their Clinical Value as a Biomarker.

BACKGROUND/AIMS: Monitoring the appearance and progression of tumors are important for improving the survival rate of patients with ovarian cancer. This study aims to examine circulating tumor cells (CTCs) in epithelial ovarian cancer (EOC) patients to evaluate their clinical significance in comparison to the existing biomarker CA125. METHODS: Immuomagnetic bead screening, targeting epithelial antigens on ovarian cancer cells, combined with multiplex reverse transcriptase-polymerase chain reaction (Multiplex RT-PCR) was used to detect CTCs in 211 samples of peripheral blood (5 ml) from 109 EOC patients. CTCs and CA125 were measured in serial from 153 blood and 153 serum samples from 51 patients and correlations with treatment were analyzed. Immunohistochemistry was used to detect the expression of tumor-associated proteins in tumor tissues and compared with gene expression in CTCs from patients. RESULTS: CTCs were detected in 90% (98/109) of newly diagnosed patients. In newly diagnosed patients, the number of CTCs was correlated with stage (p=0.034). Patients with stage IA-IB disease had a CTC positive rate of 93% (13/14), much higher than the CA125 positive rate of only 64% (9/14) for the same patients. The numbers of CTCs changed with treatment, and the expression of EpCAM (p=0.003) and HER2 (p=0.035) in CTCs was correlated with resistance to chemotherapy. Expression of EpCAM in CTCs before treatment was also correlated with overall survival (OS) (p=0.041). CONCLUSION: Detection of CTCs allows early diagnose and expression of EpCAM in CTC positive patients predicts prognosis and should be helpful for monitoring treatment.

Nanomechanical Characteristics of Cervical Cancer and Cervical Intraepithelial Neoplasia Revealed by Atomic Force Microscopy.

BACKGROUND Understanding the biological features and developmental progress of cervical cancer is crucial for disease prevention. This study aimed to determine the nanomechanical signatures of cervical samples, ranging from cervicitis to cervical carcinomas, and to investigate the underlying mechanisms. MATERIAL AND METHODS Forty-five cervical biopsies at various pathological stages were subjected to atomic force microscopy (AFM) measurements. Cdc42 and collagen I were quantified using immunohistochemical staining to investigate their relationship with nanomechanical properties of cervical cancers and premalignant lesions. RESULTS We found that the lower elasticity peaks (LEPs) in the high-grade squamous intraepithelial lesion (HSIL) group (21.24±3.83 kPa) and higher elasticity peaks (HEPs) in the cancer group (81.23±8.82 kPa) were upshifted compared with the control group (LEP at 8.51±0.18 kPa and HEP at 44.07±3.54 kPa). Furthermore, compared with the control [29.51±13.61 for cell division cycle 42 (Cdc42) expression and 28.61±17.65 for collagen I expression], immunohistochemical staining verified a significant increase of Cdc42 in the HSIL group (50.57±23.85) and collagen I (56.09±25.70) in the cancer group. In addition, using the Pearson correlation coefficient, Cdc42 expression tended to be positively correlated with LEP locations (r=0.63, P=0.012), while collagen I expression displayed a strong and positive correlation with HEP positions (r=0.88, P<0.001). CONCLUSIONS The nanomechanical properties of HSIL and cancer biopsies show unique features compared with controls, and these alterations are probably due to changes in cytoskeleton and extracellular matrix contents.

Comparison between types I and II epithelial ovarian cancer using histogram analysis of monoexponential, biexponential, and stretched-exponential diffusion models.

PURPOSE: To evaluate the utility of histogram analysis of monoexponential, biexponential, and stretched-exponential models to a dualistic model of epithelial ovarian cancer (EOC). MATERIALS AND METHODS: Fifty-two patients with histopathologically proven EOC underwent preoperative magnetic resonance imaging (MRI) (including diffusion-weighted imaging [DWI] with 11 b-values) using a 3.0T system and were divided into two groups: types I and II. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), distributed diffusion coefficient (DDC), and intravoxel water diffusion heterogeneity (α) histograms were obtained based on solid components of the entire tumor. The following metrics of each histogram were compared between two types: 1) mean; 2) median; 3) 10th percentile and 90th percentile. Conventional MRI morphological features were also recorded. RESULTS: Significant morphological features for predicting EOC type were maximum diameter (P = 0.007), texture of lesion (P = 0.001), and peritoneal implants (P = 0.001). For ADC, D, f, DDC, and α, all metrics were significantly lower in type II than type I (P < 0.05). Mean, median, 10th, and 90th percentile of D* were not significantly different (P = 0.336, 0.154, 0.779, and 0.203, respectively). Most histogram metrics of ADC, D, and DDC had significantly higher area under the receiver operating characteristic curve values than those of f and α (P < 0.05) CONCLUSION: It is feasible to grade EOC by morphological features and three models with histogram analysis. ADC, D, and DDC have better performance than f and α; f and α may provide additional information. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1797-1809.