Aims: The aim of this study was to explore HER2 status and characteristics in biopsy specimens of gastric cancer (GC) in Chinese population. Methods and results: A total of 27,787 biopsy specimens of GC from 103 hospitals were obtained. Immunohistochemistry (IHC) staining of HER2 was performed. Overall HER2 IHC positive rate was 11.2 %. HER2 positive rate elevated with the increase of age in total patients and both genders. The rates were 7.1 %, 8.1 %, 9.0 %, 10.9 %, 11.8 %, 12.6 %, and 12.1 % when patient age was <= 30, 31-40, 41-50, 51-60, 61-70, 71-80, and > 80, respectively (P < 0.001). In male, the rates were 6.5 %, 8.4 %, 9.6 %, 11.5 %, 12.4 %, 13.3 %, and 12.1 % (P < 0.001). In female, the rates were 7.4 %, 7.9 %, 8.0 %, 9.0 %, 9.6 %, 10.6 %, and 11.9% (P = 0.128). The changes in male were more dramatic than in female (P < 0.001). Furthermore, the proportion of the intestinal type GCs increased with age in total patients and both genders (P < 0.001), and in male the changes were more dramatic (P < 0.001). While the proportion of the diffuse type showed the opposite tendency to that of the intestinal type (P < 0.001). HER2 IHC positive rate showed a positive correlation with the proportion of the intestinal type (r = 0.986, P < 0.001), and a negative correlation with the proportion of the diffuse type (r = 0.984, P < 0.001). Conclusions: The HER2 IHC positive rate showed age variation in biopsy specimens of GC. In male the variation was more dramatic than in female. The variation of HER2 positive rate can be attributed to the age variation of the Lauren subtypes.

Breast cancer has obvious heterogeneity. Molecular classification of breast cancer has been done through the study of gene expression profile. There were significant differences in gene expression, clinical characteristics, therapeutic response and prognosis among these molecular types, which were lumen A type, lumen B type, her-2 overexpression type and basal cell type, respectively. Compared with other nucleic acid level detection technologies, immunohistochemistry (IHC), as the most commonly used protein expression level detection method, has the advantages of low price, short cycle and more stable. IHC staining, including ER, PR, Ki-67, Her-2, CK5/6 and EGFR, can be used to classify breast cancer into different molecular subtypes and assist in the determination of treatment options. The application of artificial intelligence in pathological morphology is in the ascendant. Different algorithms can be used to evaluate both IHC staining and HE staining morphological evaluation of tumor tissues (including histological grading).In the molecular typing of breast cancer by IHC, the digital slide images obtained by scanning with software analysis can greatly reduce the subjectivity and instability of manual evaluation and improve the repeatability. Firstly, we scanned whole slide digital image of the HE staining slides and the six IHC slides of 200 surgical specimens of breast cancer with different molecular types (non-special types) from a medical center (Peking Union Medical College Hospital).Then compare the immunohistochemical results of each case obtained manually, adjust the algorithm, calibrate the parameters in the software, and finally get the fixed algorithm code and parameters. The algorithms used in study include image classification, nuclei segmentation, channel association and image registration. The algorithms were verified in the other surgical resection specimens of 400 cases of breast cancer with different molecular types (non-special types) from two other medical center, and was compared with the data obtained by manual reading. Finally, the results were encouraging, with the consistency of molecular classification reaching 100%. This study shows AI technology has great application prospect in pathological diagnosis of breast cancer.Citation Format: Jean J. Zhao, Minzi Ruan, Quancai Cui. Artificial intelligence aided diagnosis of breast cancer molecular classification based on immunohistochemical images [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-279.

A small number of non-small cell lung cancer (NSCLC) cases showed heterogeneity of anaplastic lymphoma kinase (ALK) by VENTANA immunohistochemistry (IHC) in clinical practice. According to the ALK Scoring Interpretation Guide for VENTANA anti-ALK (D5F3), the presence of strong granular cytoplasmic staining in tumor cells (any percentage of positive tumor cells) is called positive for ALK. However, we know little about ALK heterogeneous cases. Multiple detection platforms are used to analyze molecular variability and pathological features in anticipation of clinical treatment decisions for such cases. A total of 2228 NSCLC cases with successful ALK IHC (VENTANA, D5F3, Roche) detection in Guangdong Provincial People`s Hospital were recruited between January 2012 and April 2018. Positive and negative system control and a negative agent control were established for each case. ALK IHC positivity was defined as the presence of strong granular cytoplasmic staining in 100% tumor cells; ALK IHC heterogeneity as the presence of strong granular cytoplasmic staining in 1-99% tumor cells; ALK IHC negativity as no tumor cells show strong granular cytoplasmic staining. Fluorescence in-situ hybridization (FISH) (Vysis ALK Break Apart FISH Probe Kit, Abbott) and next-generation sequencing (NGS) (OseqTMLung Cancer Gene Detection, BGI, China) was performed for cases showed ALK (D5F3) IHC heterogeneity. ALK (D5F3) double-blind review analysis showed 201 (9.0%) ALK-positive cases, 10 (0.4%) ALK-heterogeneous cases, and 2017 (90.5%) ALK-negative cases. The heterogeneity cases included 2 large cell neuroendocrine carcinomas, 1 lymphoid epithelioid carcinoma, and 7 squamous cell carcinomas. The percentages of tumor cells with strong granular cytoplasmic staining were 1% to 30%. The ALK FISH break apart signal of these ten cases were 0% to 12%, indicating ALK FISH negativity. Nine ALK-heterogeneous cases were successfully detected by NGS, and no ALKgene variations (including gene fusion, copy number variation, insertion/deletion or single nucleotide variation) were found. Immunohistochemical staining showed that some ALK-heterogeneous cases showed neuroendocrine differentiation.TableComparison of IHC, FISH and NGS results of the ALK-heterogeneous cases.Case No.GenderAgeBiopsy/surgeryDiagnosisTumor cell contentALK IHCALK FISHALK FISHALK NGSALK NGS8thTNMStrong positive staining tumor cellsBreak apart signalInterpretation resultALK fusionALK INDEL/SNV/CNV1M69Wedge resectionLarge cell neuroendocrine carcinoma70%2%0%NegativeNegativeNegativepT1bN0M02M55LobectomyLarge cell neuroendocrine carcinoma85%20%4%NegativeNegativeNegativepT2bN0M03F33LobectomyLymphoid epithelioid carcinoma60%5%0%NegativeNegativeNegativepT3N0M04M68LobectomySquamous cell carcinoma70%5%6%NegativeNegativeNegativepT3N0M05M69LobectomySquamous cell carcinoma70%5%12%NegativeNegativeNegativepT2aN0M06M52LobectomySquamous cell carcinoma80%1%0%NegativeNegativeNegativepT2aN1M07M73LobectomySquamous cell carcinoma90%5%2%NegativeNegativeNegativepT3N0M08M70LobectomySquamous cell carcinoma80%5%4%NegativeNegativeNegativepT2bN1M09M69BiopsySquamous cell carcinoma85%15%0%NegativeNegativeNegativesT3N1M010M60BiopsySquamous cell carcinoma85%30%0%NegativeNANAcT2bN3M0Abbreviations: INDEL, insertion and deletion; SNV, single nucleotide variation; CNV, copy number variation; NA, NGS was not performed due to insufficient tumor tissues. Open table in a new tab Abbreviations: INDEL, insertion and deletion; SNV, single nucleotide variation; CNV, copy number variation; NA, NGS was not performed due to insufficient tumor tissues. Multi-platform detection of ALK-heterogeneous cases did not show evidence of ALKgene variation, and the effect of ALK-TKI treatment was unknown. therefore, the VENTANA ALK scoring interpretation guide for non-small cell lung carcinoma should be revised. It is recommended that ALK-heterogeneous cases be defined as ALK (D5F3) uncertain equivocal cases. The molecular pathology report should clearly state that the clinical significance is unclear, and it is recommended to conduct further testing by FISH or NGS.

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. 1441G>A may associate with biparental complete moles. Biparental complete moles exhibit genetic heterogeneity.

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.

Objective: To investigate human epidermal growth factor 2 (HER2) gene status and in situ mRNA expression in breast cancers with immunohistochemistry(IHC) 1+ , and to reveal HER2 positive rate in these patients to provide reference data for obtaining precise HER2 results and modifying relevant clinical strategy to breast cancer. Methods: Sixty-five IHC 1+ formalin-fixed and paraffin-embedded samples of invasive breast carcinoma of no special type (IBC-NST) were collected by surgical operation at Peking Union Medical College Hospital during 2011 to 2013. HER2 status and in situ mRNA expression were tested by fluorescence in situ hybridization (FISH) and RNAscope, respectively, by using tissue microarray. Metastatic lymph node was re-tested by FISH if HER2 status was equivocal or negative and with high expression of mRNA in the primary lesion. Results: Four of 65 samples (6.2%) were FISH positive, which included 2 cases of HER2/CEP17>2 and average HER2 copy number>4 and 2 cases of HER2/CEP17<2 and average HER2 copy number>6. In the 4 samples of HER2 positive, 2 patients showed high in situ mRNA expression (3 scores by RNAscope), 2 patients showed moderate in situ mRNA expression (2 scores by RNAscope). In addition, 3 specimens with HER2/CEP17>2 and average HER2 copy number<4 were found in all patients, which included 2 cases of high in situ mRNA expression (3 and 4 scores by RNAscope) and 1 cases of moderate in situ mRNA expression (2 scores by RNAscope). There was no significant association between HER2 status or mRNA expression and clinicopathological characteristics, including tumor size, histopathological differentiation, lymph node metastasis and lymphovascular invasion (P>0.05). Conclusions: A small number of HER2 IHC 1+ patients exist mRNA expression by using FISH method, which suggested that these patients might benefit from anti-HER2 therapy potentially. Since the importance for patients with breast cancers to develop diagnostic and therapeutic strategies from accurate molecular typing, further studies based on a larger cohort are needed to validate our findings.

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.

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 αvβ3 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 αvβ3, 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 αvβ3 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.

Background and ObjectivesTo 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.MethodsMTC samples were obtained for H&E and immunohistochemical analysis. Survival analysis was performed using Kaplan-Meier method and log-rank test.ResultsBoth 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 ((2)=8.44, P=0.004).ConclusionOur 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. J. Surg. Oncol. 2016;113:144-151. (c) 2016 Wiley Periodicals, Inc

目的 探讨恶性胸膜间皮瘤(malignant pleural mesothelioma,MPM)的临床病理特征及诊断与鉴别诊断.方法 对64例MPM的临床病理特征、免疫表型、p16基因FISH检测结果进行分析,并复习相关文献.结果 64例MPM中男性43例,女性21例,发病年龄12～ 78岁.标本获得方式包括手术切除(14/64,21.9％),胸腔镜下切取活检(18/64,28.1％)及粗针穿刺活检(32/64,50％).组织学亚型包括上皮样型41例,双相型20例以及肉瘤样型3例.对其中46例MPM及另外24例间皮增生的患者进行p16基因纯合性缺失FISH检测,46例MPM中成功检测29例,发现15例存在p16基因的纯合性缺失(15/29,51.7％),而24例间皮增生中仅见1例(该例镜下间皮细胞增生十分显著,后经随访证实为间皮瘤).对15例p16基因纯合性缺失的MPM患者进行随访,其中7例在诊断后的1年内死亡(随访1～12个月),3例存活至今(随访5～17个月),中位生存时间9个月,另5例失访.结论 MPM是一种少见但发病率逐年上升的恶性肿瘤,目前的治疗手段效果欠佳,预后差.其组织学形态多样,诊断困难,应用免疫组化对诊断与鉴别诊断有很大帮助,而p16基因纯合性缺失FISH检测则对良、恶性间皮增生的鉴别有重要意义.

To assess the efficacy and safety of Moluodan (ae (c) c1/2ua(1)) in treating dysplasia in chronic atrophic gastritis (CAG) patients.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.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%.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].

Non-neoplastic epithelial disorders of the vulva (NNEDV) are common types of vulval lesions. Although corticosteroids represent a first-line treatment for NNEDV, concerns exist about the safety associated with long-term topical corticosteroid use. Recently, several clinical trials have identified high-intensity focused ultrasound (HIFU) as a promising treatment modality for NNEDV. The aim of this multi-center, randomized, controlled clinical trial was to investigate the efficacy of HIFU therapy in women with NNEDV based on histological alterations. We enrolled patients who were clinically diagnosed with NNEDV. They were randomized into 2 treatment groups: 1) halcinonide for 3 months or 2) HIFU once. A total of 123 patients were biopsied both prior to and after the therapy, and 62 and 61 patients were assigned to the HIFU and halcinonide groups, respectively. The histological changes were then analyzed. After the treatments, the therapeutic effects were observed in both groups. Comparing the diagnosis and alterations in lichenoid and sclerotic patterns and in chronic inflammation, we found statistically significant differences. Furthermore, when compared with the halcinonide group, the HIFU group exhibited enhanced curative effects that were statistically significant (P = 0.039). Based on the histological evidence from this randomized, controlled trial, HIFU represents an effective method for the treatment of NNEDV.

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.

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.

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.

Objective: To identify a subset of patients with stage IA2-IB1 cervical cancer and small tumors (<= 2 cm) 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 2 cm (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 Ull (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. (C) 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

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.

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.

Objective To investigate in situ mRNA expression of HER 2 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 HER 2 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 HER 2 gene amplification or protein overexpression , and has potential clinical utility.

Abstract Purpose: The unfolded protein response (UPR) in the endoplasmic reticulum (ER) is an adaptive mechanism for cancer cell survival manifested in many different tumors. In UPR, p97 is an AAA ATPase essential for the degradation of the misfolded proteins, a process also known as the ER-associated protein degradation (ERAD). Previous studies have shown that small molecule inhibitors targeting the key players of UPR and ERAD can inhibit tumor growth. However, the efficacy of these inhibitors has not been compared, and it is unknown whether they affect the population of cancer stem cells (CSC). The purpose of this study is to systematically study the effect of these inhibitors on the growth and differentiation of multiple tumors. Methods: Immunohistochemistry was performed to verify the upregulation of UPR and ERAD proteins in multiple cancers. Immunoblotting and reserve transcription PCR were used to examine the protein expression and the splicing of XBP-1. MTS, Annexin V-PI and Transwell assays were used to measure the proliferation, apoptosis and invasion of cancer cells in vitro. The sphere culture and flow cytometry were used to evaluate the percentage of mammary CSCs. Xenograft tumor model in nude mice was used to evaluate the growth and differentiation of breast cancer cells in vivo. Results: We found that p97, together with IRE1α, BiP/GRP78, ATF6α and ubiquitin, is up-regulated in multiple cancers when compared with the surronding non-cancerous tissues, and these proteins are expressed to different extent in eight solid and four blood tumor cell lines, which may reflect different degrees of UPR activation in these tumors. PERK and eIF2α are also phosphorylated in several tumor cells under normal culture condition, although no splicing of XBP-1 was detected. When cultured in low glucose condition, UPR activation is significantly increased. The inhibitors against IRE1α, PERK, ATF6α and p97 retard the proliferation of different tumor cells with different efficacy, while only p97 inhibitor induces significant apoptosis under normal culture condition. When combined with cisplatin or bortezomib, p97 inhibitor significantly increases cytotoxicity. Among all the inhibitors targeting UPR and ERAD, only p97 inhibitor significantly decreases the percentage of mammary CSC subpopulation of in vitro cultured MDA-MB-231 cells. P97 inhibitor also decreases tumor growth in vivo and reduces the CSC percentage in the tumor isolated from nude mice. Mechanistically, p97 inhibitor impairs the mammosphere forming and the cancer cell invasion through the inactivation of NF-κB signaling. Conclusion: Our comprehensive study demonstrates that the p97 inhibitor not only significantly reduces the growth of multiple tumors but also the CSC subpopulation, the major cause of tumor metastasis, recurrence and chemotherapy resistance, thus establishing p97 as a prime druggable target in the UPR pathway for interventional cancer therapy. Citation Format: Chuang Li, Meng Nie, Hongyang Quan, Qianqian Fan, Nan Zhang, Quancai Cui, Lin Wang. Identification of p97 as a prime target to inhibit cancer growth and stemness. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1259. doi:10.1158/1538-7445.AM2015-1259