Identification and injury to the inferior hypogastric plexus in nerve-sparing radical hysterectomy.

Waterjet dissection of the inferior hypogastric plexus (IHP) resulted in a more rapid return of normal urodynamics than blunt dissection (control group) in patients who received laparoscopic nerve-sparing radical hysterectomy (NSRH) in a randomized controlled study. However, the definite reasons for these results were unknown. This subgroup analysis compared the neural areas and impairment in the IHP uterine branches harvested during NSRH as an alternative to the IHP vesical branches between the waterjet and control groups. This study included samples from 30 eligible patients in each group of the trial NCT03020238. At least one specimen from each side of the IHP uterine branches was resected. The tissues were scanned, images were captured, and the neural component areas were calculated using the image segmentation method. Immunohistochemical staining was used to evaluate neural impairment. The control and waterjet groups had similar areas of whole tissues sent for evaluation. However, the control group had significantly fewer areas (median 272158 versus 200439 µm2, p = 0.044) and a lower percentage (median 4.9% versus 3.0%, p = 0.011) of neural tissues. No significant changes in immunohistochemical staining were found between the two groups. For patients with residual urine ≤100 and >100 ml at 14 days after NSRH (42 and 18 patients, respectively), there were significantly different percentages of neural tissues in the resected samples (p < 0.001). Hence, Due to the accurate identification of IHP during NSRH, the waterjet dissection technique achieved better urodynamic results.

NLRP7 and KHDC3L variants in Chinese patients with recurrent hydatidiform moles.

OBJECTIVE: Recurrent hydatidiform moles are reportedly biparental complete moles and related to mutated NLRP7 and KHDC3L. This study was designed to identify mutations of gene NLRP7 and KHDC3L in biparental complete moles. METHODS: In this study, we have screened NLRP7 and KHDC3L mutations in five patients with recurrent moles and five with sporadic moles. Molar tissues and blood samples were collected from patients and their partners. Genotypes of the molar tissues were determined based on short tandem repeat polymorphism. The coding exons of NLRP7 and KHDC3L were sequenced. RESULTS: Two patients with recurrent moles had biparental complete moles, while all other patients had androgenetic complete moles. Three non-synonymous variants in NLRP7 (c.955 G>A, c.1280 T>C and c.1441 G>A) and one in KHDC3L (c.602 C>G) were identified in patients with recurrent moles. NLRP7 c.1441 G>A and c.1280 T>C were mutations found in the Chinese population, while c.1441 G>A was only detected in patients with biparental complete moles in this study. CONCLUSIONS: Genotyping can be used to differentiate biparental complete moles from androgenetic moles and to predict the risk of recurrent moles in future pregnancies. NLRP7 c.1441 G>A may associate with biparental complete moles. Biparental complete moles exhibit genetic heterogeneity.

Integrin Imaging with 99mTc-3PRGD2 SPECT/CT Shows High Specificity in the Diagnosis of Lymph Node Metastasis from Non-Small Cell Lung Cancer.

Purpose To evaluate an integrin imaging approach based on single photon emission computed tomography (SPECT)/computed tomography (CT) by using technetium 99m (99mTc)-dimeric cyclic arginine-glycine-aspartic acid (RGD) peptides with three polyethylene glycol spacers (3PRGD2) as the tracer to target the integrin αvß3 expression in lung cancer and lymph node metastasis. Materials and Methods With ethics committee approval and written informed consent, 65 patients (41 male, 24 female; mean age, 60 years ± 11 [standard deviation]) with suspicious lung lesions were recruited with informed consent. The patients underwent both 99mTc-3PRGD2 SPECT/CT and fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT within 1 week. Finally, 65 lung lesions in 53 patients were pathologically diagnosed as non-small cell lung cancer (NSCLC) and 14 lung lesions in 12 patients were benign. Per-region analysis of lymph nodes included 248 regions with metastasis and 56 negative regions. Twenty specimens from the removed lung lesions or lymph nodes were stained with integrin αvß3, CD34, and Ki-67 to correlate with the image findings. Receiver operating characteristic curve, z statistics, McNemar test, and χ2 analysis were used to compare the diagnostic performance of the two imaging methods. Results 99mTc-3PRGD2 SPECT/CT was found to be more specific than 18F-FDG PET/CT in the per-region diagnosis of lymph node metastasis (specificity, 94.6% vs 75.0%; P = .008) when the sensitivity of the two methods was comparable (88.3% vs 90.7%; P = .557). There was no significant difference between the two methods in the per-lesion diagnosis of lung tumor (z = 0.82, P = .410). The accumulation level of 99mTc-3PRGD2 was found in positive correlation with the integrin αvß3 expression (r = 0.84, P = .001) and microvessel density (r = 0.63, P = .011) in the tumors. Conclusion 99mTc-3PRGD2 SPECT/CT shows high specificity in the diagnosis of lymph node metastasis from NSCLC, which may benefit surgical decision making for the patients. © RSNA, 2016.

Accuracy of conization procedure for predicting pathological parameters of radical hysterectomy in stage Ia2-Ib1 (≤2 cm) cervical cancer.

The accuracy of conization for the prediction of radical hysterectomy (RH) pathological variables in patients with stage Ia2 to Ib1 (≤2 cm) cervical cancer was retrospectively evaluated in the present study. Endocervical or deep resection margin (RM) involvement in the conization specimens was found to be independently associated with residual disease in the hysterectomy specimens (P < 0.001, = 0.003, respectively). When a tumor width of >20 mm in the final RH pathology analysis was predicted by a tumor width of >2 mm or involvement of endocervical or deep RMs in the conization specimens, the sensitivity and negative predictive value (NPV) of conization were 98.2% and 95.2%, respectively. In addition, when deep stromal invasion in the final RH pathology analysis was predicted by deep stromal invasion or involvement of the endocervical or deep RMs in the conization specimens, the sensitivity and NPV of conization were 98.4% and 95.8%, respectively. The sensitivity and NPV of this prediction model for identifying LVSI in the final RH pathology analysis were both 100%. These findings suggest that conization variables and endocervical and deep resection margin statuses can be analyzed to effectively predict RH pathological parameters.

Expression of the potential cancer stem cell markers CD133 and CD44 in medullary thyroid carcinoma: A ten-year follow-up and prognostic analysis.

BACKGROUND AND OBJECTIVES: To investigate the expression profiles of cancer stem cells (CSCs) markers CD133 and CD44 in a cohort of medullary thyroid carcinoma (MTC) patients, and their prognostic values during 10-year follow-up. METHODS: MTC samples were obtained for H&E and immunohistochemical analysis. Survival analysis was performed using Kaplan-Meier method and log-rank test. RESULTS: Both the CD133 and CD44 positives were higher in MTC than control. High expression of CD133 and CD44 was positively correlated with capsule invasion and each other, and their co-expression was significantly correlated with capsule invasion, tissue invasion, and metastases at surgery. Tumor size, capsular invasion, tissue invasion, metastases at surgery, surgical plan, lymph node metastases, TNM stage, CD133, and CD44 were prognostic factors for overall survival (OS) and/or disease free survival (DFS). Both the CD133 and CD44 were unfavorable prognostic predictors for OS (P = 0.046, P = 0.03), while only CD44 was a significant predictor for DFS (P = 0.017). OS rate in CD133/CD44 co-expression group was significantly lower than that in non-co-expression group (χ(2) = 8.44, P = 0.004). CONCLUSION: Our study suggested the high expression of CD133 and CD44 in the MTC, and CD133 and CD44 expressions were correlated with capsule invasion and with OS. CD133 and/or CD44 may be prognostic factors for OS and/or DFS in our MTC patients.

Randomized double-blind clinical trial of Moluodan () for the treatment of chronic atrophic gastritis with dysplasia.

OBJECTIVE: To assess the efficacy and safety of Moluodan () in treating dysplasia in chronic atrophic gastritis (CAG) patients. METHODS: This was a multi-centered, double-blind, randomized controlled trial. The total of 196 subjects were assigned to receive either Moluodan or folic acid in a 2:1 ratio by blocked randomization. Mucosa marking targeting biopsy (MTB) was used to insure the accuracy and consistency between baseline and after 6-month treatment. Primary outcomes were histological score, response rate of pathological lesions and dysplasia disappearance rate. Secondary endpoints included gastroscopic findings, clinical symptom and patient reported outcome (PRO) instrument. RESULTS: Dysplasia score decreased in Moluodan group (P =0.002), significance was found between groups (P =0.045). Dysplasia disappearance rates were 24.6% and 15.2% in Moluodan and folic acid groups respectively, no significant differences were found (P =0.127). The response rate of atrophy and intestinal metaplasia were 34.6% and 23.0% in Moluodan group, 24.3% and 13.6% in folic acid group. Moluodan could improve erythema (P =0.044), and bile reflux (P =0.059), no significance between groups. Moluodan was better than folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite (P <0.05), with symptom disappearance rates of 37% to 83%. CONCLUSIONS: Moluodan improved dysplasia score in histopathology, and erythema and bile reflux score in endoscopy, and superior to folic acid in improving epigastric pain, epigastric suffocation, belching and decreased appetite. [ChiCTR-TRC-00000169].

[HER2 mRNA expression in breast cancers with equivocal immunohistochemical results using in situ mRNA hybridization].

OBJECTIVE: To investigate in situ mRNA expression of HER2 oncogene in breast cancers with equivocal immunohistochemical results, and to explore the potential feasibility of RNAscope technique in evaluating HER2 status in breast cancers. METHODS: Sixty-nine FFPE samples of invasive ductal breast cancer with equivocal HER2 immunohistochemistry results (IHC 2+) were collected from surgical excisions from Peking Union Medical College Hospital between June 2010 and June 2013. HER2 status and in situ mRNA expression were tested by fluorescence in situ hybridization (FISH) and RNAscope respectively using tissue microarray constructed from tumor paraffin blocks. The results of HER2 mRNA expression were scored 0 to 4 (from low to high levels) according to mRNA expression in 100 cancer cells. HER2 mRNA expression was evaluated in two groups of patients, with positive and negative FISH results. RESULTS: Twenty-three of the 69 samples were FISH positive, including 16 samples that were scored 4 by RNAscope (70%, 16/23), 6 samples were scored 3 (26%, 6/23) and one sample was scored 2 (4%, 1/23). High in situ mRNA expression (score 4 or 3) were observed in 96% of HER2 FISH positive samples. All of samples that were scored 4 by RNAscope were FISH positive. Forty-six samples were FISH negative, including 17 samples that were scored 3 by RNAscope (37%, 17/46), 25 samples were scored 2 (54%, 25/46), and 4 samples were scored 1 (9%, 4/46). CONCLUSIONS: Breast cancer with HER2 IHC 2+ could be further classified according to in situ mRNA expression status. Among them, RNAscope score of 4 could be one of the interpretation criteria for re-testing IHC 2+ samples. In situ detection of HER2 mRNA may be an additional candidate method of confirmation for HER2 gene amplification or protein overexpression, and has potential clinical utility.

The first attempt in local excision of anorectal malignant melanoma using transanal endoscopic microsurgery.

Anorectal malignant melanoma (AMM) is an uncommon malignancy that is thought to arise from melanocytes in the mucosa around the anorectal junction. AMM is commonly misdiagnosed, and definitive preoperative diagnosis is often difficult. The prognosis of AMM is relatively poor. Although radical resection is required for AMM, there is still no consensus at this moment on which surgical approach is preferred. We herein report a rare case of AMM which was treated by transanal endoscopic microsurgery (TEM) in combination with radiotherapy, which resulted in complete excision of the lesion without complications. The successful treatment for this AMM using TEM emphasizes the need to broaden its application in the treatment of various rectal lesions while preserving organ function and decreasing recurrence.

[Expression of EpCAM and E-cadherin in papillary thyroid carcinoma and its clinicopathologic significance].

OBJECTIVE: To study the expression of EpCAM and E-cadherin in papillary thyroid carcinoma and to analyze its correlation with various clinicopathologic parameters. METHODS: Immunohistochemical study for EpCAM and E-cadherin was carried out in 91 cases of papillary thyroid carcinoma. Twenty-four cases of papillary hyperplasia of thyroid were used as controls. RESULTS: In all of the 24 cases of papillary hyperplasia, EpCAM was located on the cell membrane, while in the 91 cases of papillary thyroid carcinoma studied, EpCAM was located within the cytoplasm, with 36.3% (33/91) showing nuclear localization as well. In all the papillary hyperplasia cases studied, E-cadherin showed membranous expression. E-cadherin expression was reduced in 84.6% (77/91) of papillary thyroid carcinoma, as compared with the surrounding native thyroid parenchyma. Amongst the 33 cases of papillary thyroid carcinoma which showed nuclear localization of EpCAM, 30 cases also showed reduced E-cadherin expression. There was a positive correlation between nuclear expression of EpCAM and loss of E-cadherin expression (P = 0.000; Spearman correlation coefficient = 0.857). Nuclear expression of EpCAM correlated with follicular variant of papillary thyroid carcinoma and presence of extrathyroidal extension ( P = 0.037 and 0.033, respectively). Loss of E-cadherin expression correlated with age of patients and presence of lymph node metastasis (P = 0.018 and 0.010, respectively). CONCLUSIONS: E-cadherin expression is reduced in papillary thyroid carcinoma, as compared with native thyroid parenchyma and papillary hyperplasia. Papillary thyroid carcinoma shows loss of EpCAM membranous expression and increased cytoplasmic/nuclear accumulation. Detection of these two markers may provide a valuable reference in defining the biologic behaviors of papillary thyroid carcinoma, including extrathyroidal extension and lymph node metastasis.

The potential for less radical surgery in women with stage IA2-IB1 cervical cancer.

OBJECTIVE: To identify a subset of patients with stage IA2-IB1 cervical cancer and small tumors (≤2cm) who could be suitable for less radical surgery. METHODS: In a retrospective study, the medical records of women treated at nine hospitals in China were reviewed. Included women had undergone radical hysterectomy and pelvic lymph node dissection. The clinicopathologic factors associated with uterine isthmus invasion (UII), vaginal invasion (VI), parametrial invasion (PI), lymph node metastasis (LNM), and prognosis were analyzed. RESULTS: Overall, 1632 women were included. Tumor size greater than 2cm (measured postoperatively) was an independent predictor of VI (P=0.002), PI (P=0.001), and UII (P=0.021). Squamous cell carcinoma and superficial stromal invasion were associated with a low frequency of UII (P<0.001 for both). Among patients with adenocarcinoma, deep stromal invasion and lymphovascular space involvement (LVSI) were independently associated with UII (P=0.006 and P=0.004, respectively). Grade 2/3 disease (P=0.009), deep stromal invasion (P=0.015), and LVSI (P<0.001) were independently associated with LNM. LNM was the only independent adverse factor for survival (P<0.001). CONCLUSION: Women with stage IA2-IB1 cervical cancer with low-risk factors could be candidates for large-scale prospective clinical trials of less radical surgery and lymphadenectomy omission.

Expression of c-fos was associated with clinicopathologic characteristics and prognosis in pancreatic cancer.

It has long been regarded that pancreatic cancer (PC) is a life-threatening malignant tumor. Thus, much attention has been paid for factors, especially relative molecules, predictive for prognosis of PC. However, c-fos expression in PC was less investigated. In addition, its association with clinicopathologic variables and prognosis remains unknown. In the present study, expression of c-fos was detected by tissue microarray-based immunohistochemical staining in cancer and adjacent tissues from 333 patients with PC. The staining results were correlated with clinicopathologic parameters and overall survival. Furthermore, prognostic significance of c-fos in subsets of PC was also evaluated. It was shown that low expression of c-fos was more often in cancer than in adjacent tissues of PC (P<0.001). Besides, high cancerous c-fos expression was significantly associated with tumor site and T stage, whereas peri-neural invasion was of a borderline significant relevance. Log-rank test revealed that high expression of c-fos in cancer tissues was a significant marker of poor overall survival, accompanied by some conventional clinicopathologic variables, such as sex, grade, peri-neural invasion, T and N stages. More importantly, cancerous c-fos expression was identified as an independent prognosticator in multivariate analysis. Finally, the prognostic implication of c-fos expression was proven in four subsets of patients with PC. These data suggested that c-fos expression was of relationships with progression and dismal prognosis of PC.

Overexpression of eukaryotic translation initiation factor 5A2 (EIF5A2) correlates with cell aggressiveness and poor survival in gastric cancer.

Eukaryotic translation initiation factor 5A2 (EIF5A2) plays an important role in tumor progression and prognosis evaluation. However, little information is available about its potential role in gastric cancer. This study aimed to investigate the function of EIF5A2 in tumor progression and its potential mechanisms. EIF5A2 expression was measured in human gastric cancer cell lines, the immortalized gastric mucosal epithelial cell line (GES-1) and human gastric cancer tissues and knocked down by RNA interference or upregulated by EIF5A2 plasmid transfection. Cell proliferation, migration and invasion were assessed in vitro. The downstream targets of EIF5A2 were examined by western blotting. EIF5A2 and its potential target metastasis-associated protein 1 (MTA1) expression were examined in 160 pairs of human gastric cancer and adjacent non-tumor specimens using immunohistochemistry (IHC) staining, and its correlation with clinicopathological features and survival was investigated. Knockdown of EIF5A2 or MTA1 caused an apparent suppression of HGC27 cell proliferation, migration and invasion. After knockdown of EIF5A2 in HGC27 cells, E-cadherin levels were upregulated and vimentin, cyclin D1, cyclin D3, C-MYC and MTA1 levels were downregulated. Upregulation of EIF5A2 in MKN45 cells resulted in the converse. IHC results showed a positive correlation between EIF5A2 and MTA1 expression in gastric cancers (P<0.001). Both EIF5A2 and MTA1 overexpression were correlated with pT stage (P=0.018 and P=0.042), pN stage (P=0.037 and P=0.020) and lymphovascular invasion (P=0.016 and P=0.044). EIF5A2 or MTA1 overexpression was significantly associated with poor overall survival and disease-free survival (All P<0.05). Multivariate analyses identified EIF5A2 as an independent predictor for both overall survival (P=0.012) and disease-free survival (P=0.008) in gastric cancer patients. Our findings indicate that EIF5A2 upregulation plays an important oncogenic role in gastric cancer. EIF5A2 may represent a new predictor for poor survival and is a potential therapeutic target for gastric cancer.

Surgical resection improves the outcome of the patients with neuroendocrine tumor liver metastases: large data from Asia.

How to properly manage neuroendocrine liver metastasis (NELM) remains debatable, and only limited clinical data have been published from Asian population. The objective of this study is to identify possible prognostic factors affecting overall survival time and to provide a guideline for future clinical practice. A retrospective study was performed on 1286 patients who had neuroendocrine tumors in our specialized center, and data from 130 patients who had NELM were summarized. Demographic and clinicopathologic data, tumor grade, treatment method, and prognosis were statistically analyzed. Most of the NELMs originated from pancreas (65.4%). Important prognostic factors that included tumor location and size were identified with multivariate analysis. Patients with either primary tumor resection or liver metastasis resection showed a 5-year survival of 35.7% or 33.3%, respectively, whereas resection of both resulted in a 50% 5-year survival. More importantly, resection was performed on 7 patients with grade 3 (G3) tumors, and resulted in 1-year, 3-year, and 5-year survival of 100%, 42.8%, and 28.6%, respectively, whereas the other 9 G3 patients without resection died within 3 years. P = 0.49 comparing the resected group with nonresected group in G3 patients. Besides, the overall 5-year survival rates for resected and nonresected patients were 40.5% and 5.4%, respectively. Multiple prognostic factors influenced the overall outcome of NELM including patient age, tumor location, and size, etc. Aggressive surgical approaches could be considered for maximum survival time disregarding the pathological grade of the tumor. Study with larger sample size should be considered to reevaluate the recommendation of the WHO guidelines for G3 neuroendocrine tumors.

Angiosarcoma of the pericardium: a case report.

BACKGROUND: Primary malignant tumors of the pericardium are rare, and most primary malignant pericardium tumors are mesotheliomas. Primary pericardial angiosarcoma is extremely rare, and it is associated with a poor prognosis. CASE PRESENTATION: We report of a 47-year-old woman who complained of activity-related chest tightness and shortness of breath. Computed tomography, magnetic resonance imaging, and transesophageal echocardiography revealed an enlarged pericardium with hematic and solid components. An exploratory pericardiotomy was performed, and the results of the histological examination were suggestive of spindle cell hemangioendothelioma. She survived for 9 months after surgery without chemotherapy and radiotherapy, and she had a relatively good quality of life. CONCLUSION: Primary pericardial angiosarcoma is difficult to diagnose, and it has a poor prognosis. Pericardiotomy, radiation therapy, and chemotherapy were associated with a prolongation of survival.

Castleman disease variant of POEMS syndrome complicated with multiple cerebral infarction: a rare case report and review of literature.

POEMS syndrome is a rare hematological disorder associated with plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. Castleman disease is a lymphoproliferative disorder that can be present in POEMS patients, which can be defined as Castleman disease variant of POEMS syndrome. Herein, we described a 24-year-old male patient diagnosed with this syndrome and also suffered from multiple cerebral infarctions. This patient showed no evidence of monoclonal gammopathy and failed to have electromyography examined. The final diagnosis was established with the help of the axillary lymph node biopsy. As a rare case of POEMS syndrome without evidence fulfilling the major mandatory diagnostic criteria and with cerebrovascular involvement, its characteristics was discussed with a brief literature review in order to facilitate further understanding of the POEMS syndrome.

Recurrent painful perianal subcutaneous angiomatoid fibrous histiocytoma: a case report and review of the literature.

Angiomatoid fibrous histiocytoma (AFH) is a rare, low-grade malignant soft-tissue tumor most commonly occurring in the extremities of children and young adults and has a low potential of local recurrence and metastasis. Here, we present a case of recurrent subcutaneous perianal AFH. After an initial diagnosis as a sebaceous cyst, we were able to use immunohistochemical findings to correctly identify the mass as an AFH. The patient was effectively treated after 3 surgical resections. This case emphasizes the need to correctly diagnose soft-tissue tumors using a variety of diagnostic modalities to ensure that the patient receives proper treatment.

Epstein-Barr virus positive inflammatory pseudotumor of the liver: report of a challenging case and review of the literature.

Inflammatory pseudotumor (IPT) is an uncommon, benign lesion of unclear etiology, which is sometimes associated with Epstein-Barr virus (EBV). In this study, we discuss a case of hepatic EBV positive IPT and discuss mimickers, prognosis, and treatment. The case we describe was located in the liver and composed of a mixture of spindle cells and polymorphic inflammatory cells with areas of necrosis. The spindle cells were negative for CAM5.2, ALK1, CD21, CD23, CD35, actin, S-100, and CD34. EBV-encoded small RNA in situ hybridization showed a large number of EBV positive cells. The diagnosis of hepatic EBV positive IPT with uncertain biological behavior was issued, presenting numerous difficulties with diagnostic and therapeutic challenges.

Prognostic significance of epidermal growth factor-like domain 7 in pancreatic cancer.

BACKGROUND: Recent studies have shown the clinical significance of epidermal growth factor-like domain 7 (EGFL7) in a variety of cancers. However, the relationship between EGFL7 and the prognosis of pancreatic cancer (PC) remains unclear. The present study was undertaken to investigate the role of EGFL7 in the prognosis of PC. METHODS: The expression of EGFL7 in nine PC cell lines was first determined by Western blotting analysis. Tissue microarray-based immunohistochemical staining was performed in paired formalin-fixed paraffin-embedded tumor and non-tumor samples from 83 patients with PC. Finally, correlations between EGFL7 expression and clinicopathological variables as well as overall survival were evaluated. RESULTS: EGFL7 was widely expressed in all PC cell lines tested. EGFL7 expression in tumor tissues was significantly higher than that in non-tumor tissues (P=0.040). In addition, univariate analysis revealed that high EGFL7 expression in tumor tissues was significantly associated with poor overall survival, accompanied by several conventional clinicopathological variables, such as gender, histological grade and lymph node metastasis. In a multivariate Cox regression test, EGFL7 expression was identified as an independent marker for long-term outcome of PC. CONCLUSION: Our data showed that EGFL7 is extensively expressed in PC and that EGFL7 is associated with poor prognosis.

Tumor heterogeneity in the recurrence of epithelial ovarian cancer demonstrated by polycomb group proteins.

PURPOSE: To investigate tumor heterogeneity in the recurrence of epithelial ovarian cancer demonstrated by polycomb group (PcG) proteins. METHODS: Tissue microarrays containing matched primary and recurrent ovarian tumors from the same patients were constructed for detection of PcG protein expression. Survival analyses of clinicopathological parameters and expression of PcG proteins were performed on progression-free survival (PFS) and overall survival (OS) of patients. Genetic and epigenetic heterogeneity was explored in aspects of gene copy number and microRNA (miRNA) profiling. RESULTS: PcG proteins were heterogeneously expressed in primary versus recurrent tumors (P<0.05). In univariate survival analysis of the ovarian carcinoma cohorts, a significant association of intensive expression of BMI1 and EZH2 in first-onset lymph node metastases with shortened PFS was demonstrated (P=0.010, P=0.019); and a significant association of intensive expression of BMI1 and EZH2 in recurrent tumors with shortened OS was demonstrated (P=0.042, P=0.047). Importantly, BMI1 and EZH2 expression provided significant independent prognostic parameters in multivariate analyses (P<0.05). Gene amplification did not always coincide with PcG protein expression. Eight miRNAs were found to be downregulated in recurrent tumors, among which miR-298 might indirectly regulate the expression of EZH2 through transcription factor ILF3. CONCLUSION: Tumor heterogeneity exists in the recurrence of epithelial ovarian cancer, manifested by PcG protein expression and underlying genetic and epigenetic alterations. Intensive expression of BMI1 and EZH2 are predictors of earlier relapse and shorter OS, independent of grade and chemotherapy sensitivity. EZH2 and miR-298 have great potential to be new targets for treatment of recurrent ovarian cancer.

The prognostic value of Cyclin B1 in pancreatic cancer.

Pancreatic cancer (PC), a malignancy with very poor prognosis, presents many molecular alterations, including overexpression of Cyclin B1. However, the prognostic value of the protein in PC remains to be elucidated. In the present study, Cyclin B1 expression was detected immunohistochemically in specimens from 241 patients with PC and was correlated with clinicopathological features and patient survival. It was found that Cyclin B1 expression, located in nucleus and/or cytoplasm, was not statistically associated with clinicopathologic variables. However, overall survival of patients with high Cyclin B1 expression was significantly poorer than that of those with low Cyclin B1 expression (P = 0.010). Moreover, Cyclin B1 was identified as an independent prognostic factor by multivariate Cox regression test (P = 0.003). Finally, its independent implication for prognosis was proven in five subgroups of PC, i.e., males, patients aged ≤ 65 years, G1-2 and N0 tumors as well as those with perineural invasion (all P < 0.05). These data indicate that high expression of Cyclin B1 is a valuable molecular marker of unfavorable prognosis in PC.