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The heterogeneity of programmed death-ligand 1 (PD-L1) status between core needle biopsies (CNBs) from one tumor has not been well studied before. The current study attempts to find out the best index using multiple core biopsies from one tumor which can better reflect the actual PD-L1 status. Random CNB was performed in surgical specimens from 170 consecutive non-small cell lung cancer samples. Fifty-one cases (41 cases with PD-L1 positive and 10 cases with PD-L1 negative) and 216 matched CNBs were analyzed by DAKO 22C3 PharmDx Link 48 Autostainer. The PD-L1 status was compared between the surgical specimens and matched CNBs. Heterogeneity of PD-L1 status between CNBs from one tumor was observed in 56% of PD-L1 positive cases. Different tumor proportion score (TPS) statistical forms with regard to the highest, mean, median, weighted average TPS, as well as TPS showed by the longest biopsy specimen and the biopsy with most tumor volume were compared. At a cut-off of 1%, the concordance rates were 94.1%, 88.2%, 90.2%, 86.3%, 86.3%, and 86.3%; At a cut-off of 50%, the concordance rates were 92.2%, 86.3%, 84.3%, 82.4%, 82.4%, and 86.3%, respectively. The CNB with the highest TPS can best represent PD-L1 status estimated by whole surgical specimen. The highest TPS among the multiple biopsies is a robust evaluation of the PD-L1 status, but not mean TPS, at the 1% and 50% cut-offs.

The expression of programmed cell death ligand 1 (PD-L1) as a biomarker for immunotherapy in non-small cell lung cancer (NSCLC) is routinely detected in clinical pathology department. However, the spatial heterogeneity of PD-L1 expression in intrapulmonary tumors and extrapulmonary metastases is still a challenge for the clinical testing. This study aims to explore the differences of PD-L1 expression in test samples obtaining from different sites of NSCLC. This study may contribute to the detection strategy of PD-L1 in patients with advanced lung cancer.One hundred and thirty-one cases of consecutively detected PD-L1 (22c3 assay, Dako) staining in metastatic NSCLC and 972 cases of non-paired intrapulmonary NSCLC were collected. The discrepancies of tumor proportion score (TPS) of PD-L1 expression in intrapulmonary samples and extrapulmonary metastatic samples of different sites were compared.The positive expression rate of PD-L1 in extrapulmonary metastatic NSCLC (TPS ≥ 1%) was 61.83%, and the TPS was significantly higher than that in intrapulmonary tumors (P=0.03). The PD-L1 scores of the specimens obtained from different sites were significantly different (P=0.007). The positive rates of PD-L1 in liver and adrenal metastases were 85.71% and 77.78% respectively, and their TPS were significantly higher than that of the intrapulmonary samples (P0.05). The positive rates of PD-L1 in lymph node, bone, brain, soft tissue, and pleural metastases was 40.00%-66.67%, with no significant differences compared to intrapulmonary tumors. The analysis of histological subtype and sample type showed that the PD-L1 score of extrapulmonary samples of adenocarcinoma subtype or surgical specimen was significantly higher than that of intrapulmonary tumors. The analysis of clinicopathological parameters showed that the PD-L1 positive expression or high expression were significantly correlated with male patients, smoking history, and epidermal growth factor receptor (EGFR) wild type.The expression of PD-L1 in metastatic NSCLC is generally higher than that in intrapulmonary tumor, and the positive rate of PD-L1 expression was discrepant in different sites of specimen. The differences of PD-L1 score between extrapulmonary metastatic samples and intrapulmonary samples may be associated with different metastatic sites, histological subtype, and specimen type.【中文题目：非小细胞肺癌不同部位组织样本PD-L1 表达水平比较研究】 【中文摘要：背景与目的 程序性死亡配体1（programmed cell death ligand 1, PD-L1）作为非小细胞肺癌（non-small cell lung cancer, NSCLC）免疫治疗患者分层标志物已进入临床病理常规检测。然而PD-L1表达在肺内和肺外不同转移部位的空间异质性是困扰临床检测的难题。本研究旨在探讨NSCLC不同部位组织样本的PD-L1表达评分的差异，从而有助于晚期肺癌患者的PD-L1检测策略的制定。方法 回顾性收集PD-L1（22c3抗体，Dako）临床病理连续检测的131例肺外转移性NSCLC以及同期非配对肺内肿瘤972例进行对照分析，对比肺外与肺内肿瘤组织样本检测的PD-L1肿瘤阳性比例评分（tumor proportion score, TPS）差异。结果 肺外转移性NSCLC的PD-L1阳性表达率（TPS≥1%）为61.83%，TPS评分显著高于同期肺内肿瘤（P=0.03）。不同部位组织样本的PD-L1表达评分具有显著差异（P=0.007）。肝脏和肾上腺转移瘤的PD-L1阳性率高，分别为85.71%和77.78%，其TPS评分均显著高于肺内肿瘤（P0.05）。淋巴结、骨、脑、软组织和胸膜转移瘤的PD-L1表达率为40.00%-66.67%，TPS评分与肺内肿瘤无显著差异。组织学和样本类型分析显示，腺癌类型和手术切除的肺外样本PD-L1表达评分显著高于同类型肺内肿瘤。临床病理参数分析显示，PD-L1阳性表达和高表达均与患者男性、吸烟史以及表皮生长因子受体（epidermal growth factor receptor, EGFR）野生型显著相关。结论 肺外转移性NSCLC样本的PD-L1表达评分高于肺内肿瘤，且不同部位组织样本的PD-L1表达阳性率存在差异。肺外转移性肿瘤与肺内肿瘤的PD-L1检测差异可能与不同转移部位、组织学和样本类型相关。 】 【中文关键词：肺肿瘤；程序性死亡配体1；异质性；肿瘤阳性比例评分】.

Tumor immune cell infiltration is important in the prognosis of patients with lung adenocarcinoma. The aim of this study was to develop a prognostic classification based on the tumor immunoscore.Patients with KRAS-mutant invasive non-mucinous lung adenocarcinoma who underwent radical surgery were enrolled in the study. Histologic grading was assessed according to the recommendations of the International Association for the Study of Lung Cancer. Programmed death-ligand 1 (PD-L1) and CD8 expression was detected using immunohistochemistry. The number of CD8A total of 112 patients participated. In the multivariable analysis, histological grading and level of CD8The Grading-Immunoscore classification refines the prognostic grouping of histological grading and might aid in the screening of potential candidates for immunotherapy in patients with KRAS-mutant adenocarcinoma.

Background Adenosquamous carcinoma (ASC)with concurrent gastric carcinoma with lymphoid stroma (GCLS) are extremely rare tumors. There are only limited cases reported in the literature. Epstein–Barr virus (EBV) infection was found in the concomitant GCLS, but none in the ASC. Here, we report the first case of gastric cancer with EBV infection detected in both ASC and GCLS. Case presentation A 59-year-old man complained of intermittent upper abdominal pain. The gastric endoscopy revealed a type IIc tumor located in the gastric body near the fundus of the stomach. Histological examination of the gastric tumor showed the coexistence of ASC and GCLS. Both components were positive for EBV-encoded RNA (EBER) in situ hybridization. Neoplastic nests of the former were positive for p63, p40 and CK5/6. The glandular components showed positive acid mucus in the Alcian-blue periodic-acid-schiff (AB-PAS) staining. There was significant difference in the expression of epidermal growth factor receptor (EGFR) between adenocarcinoma and squamous carcinoma, but not in other proteins such as human epidermal growth factor receptor 2 (HER2), p53 and mismatch repair proteins. The role of EGFR signaling pathway needs to be further explored in the differentiation of squamous carcinoma in the gastric ASC. Finally, a diagnosis of early EBV associated gastric ASC with concurrent GCLS (pT1bN1) was made. The patient took a single-drug S1 periodically for half a year after the surgery and has been disease free during 8 months of medical follow-up. Conclusions This is the first case of EBV associated gastric ASC with concurrent GCLS, and pathologists and clinicians should recognize and pay attention to this type of tumor.

Standardized programmed death-ligand 1 (PD-L1) assessment in non-small cell lung cancer (NSCLC) is challenging, owing to inter-observer variability among pathologists and the use of different antibodies. There is a strong demand for the development of an artificial intelligence (AI) system to obtain high-precision scores of PD-L1 expression in clinical diagnostic scenarios. We developed an AI system using whole slide images (WSIs) of the 22c3 assay to automatically assess the tumor proportion score (TPS) of PD-L1 expression based on a deep learning (DL) model of tumor detection. Tests were performed to show the diagnostic ability of the AI system in the 22c3 assay to assist pathologists and the reliability of the application in the SP263 assay. A robust high-performance DL model for automated tumor detection was devised with an accuracy and specificity of 0.9326 and 0.9641, respectively, and a concrete TPS value was obtained after tumor cell segmentation. The TPS comparison test in the 22c3 assay showed strong consistency between the TPS calculated with the AI system and trained pathologists (R = 0.9429-0.9458). AI-assisted diagnosis test confirmed that the repeatability and efficiency of untrained pathologists could be improved using the AI system. The Ventana PD-L1 (SP263) assay showed high consistency in TPS calculations between the AI system and pathologists (R = 0.9787). In conclusion, a high-precision AI system is proposed for the automated TPS assessment of PD-L1 expression in the 22c3 and SP263 assays in NSCLC. Our study also indicates the benefits of using an AI-assisted system to improve diagnostic repeatability and efficiency for pathologists.

Metastatic tumors (MTs) may show different characteristics of the immune microenvironment from primary tumors (PTs) in non-small cell lung cancer (NSCLC). The heterogeneity of immune markers in metastatic NSCLC and its associated factors has not been well demonstrated. In this study, 64 surgically resected specimens of paired PTs and MTs were obtained from 28 patients with NSCLC. Multiplex immunofluorescence (mIF; panel including programmed death-ligand 1 (PD-L1), Cytokeratin, CD8, and CD68) was performed on whole sections. The heterogeneity of the immune contexture of PD-L1 expression, infiltrating lymphocytes, and immune-to-tumor cell distances was quantified via digital image analysis. In a quantitative comparison of MTs and corresponding PTs, MTs showed higher PD-L1 expression levels, lower density of CD8+ cytotoxic T lymphocytes (CTLs), and longer spatial distance between CTLs and tumor cells. Subgroup analysis, which associated clinical factors, revealed that the heterogeneity of immune markers was more obvious in extrapulmonary, metachronous, and treated MTs, while fewer differences were observed in intrapulmonary, synchronous, and untreated MTs. In particular, MTs showed significantly higher PD-L1 expression and lower lymphocyte infiltration in metastatic NSCLC with EGFR mutations. Prognosis analysis showed that an increased density of CD8+ CTLs in MTs was associated with better overall survival (OS). Therefore, significant discrepancies in PD-L1 expression and lymphocyte infiltration in metastatic NSCLC are most likely associated with temporal heterogeneity with a history of anti-treatment and correlated with EGFR mutations. The detection of immune markers in re-obtained metastatic specimens may be required for immunotherapy prediction in these patients with metastatic NSCLC.

AimsThis study aimed to validate the application of combined multiplex immunofluorescence (mIF) and digital image analysis (DIA) in formalin-fixed and paraffin-embedded tissues for the quantitative assessment of programmed death-ligand 1(PD-L1) and immune cells (ICs) in non-small cell lung cancer (NSCLC).MethodsFifty resected samples of NSCLC were sequentially stained with a DNA-tagged mIF (panel including PD-L1, CKpan, CD8, CD68 and 4′,6-diamidino-2-phenylindole (DAPI)) and conventional immunohistochemistry (cIHC). The assessment of cell density and consistency of tumour proportion score (TPS) via DIA were compared with those by pathologists.ResultsA strong correlation in the cell population of immune markers was obtained between mIF and cIHC (for PD-L1: R=0.9304, CKpan: R=0.8231, CD8: R=0.9314 and CD68: R=0.8366) within 95% limits of agreement. The continuous TPS calculated using mIF was highly consistent with the IHC staining results which were evaluated by pathologists (R=0.9362). However, in the comparison of TPS using interval variables, a poor agreement was obtained at a cut-off of 1% (κ=0.197), whereas excellent agreement was achieved at cut-offs of 50% (κ=0.908) and 5% (κ=0.823). DIA on mIF showed that PD-L1 commonly colocalised with CD68+ macrophages and CD8+ cytotoxic cells were closer to PD-L1-/CK+ tumour cells (TCs) than to PD-L1+/CK+ TCs in spatial distribution.ConclusionsA combination of mIF and DIA is useful for the quantification of PD-L1 expression and IC populations in NSCLC. Further validation of TPS at a cut-off of 1% and assay harmonisation is essential for translating this method in a diagnostic setting.

Aquaporin 3 (AQP3) is the membrane channel of water and involved in fluid homeostasis. The aim of this study was to reveal the expression and significance of AQP3 in cutaneous lesions. We analyzed AQP3 mRNA levels using RT-PCR in 311 cutaneous lesions and confirmed AQP3 expression in these lesions by immunohistochemistry. AQP3 mRNA was detected in normal epidermis, seborrheic keratosis, solar keratosis, Bowen’s disease, squamous cell carcinoma, eccrine poroma, apocrine carcinoma, and sebaceoma; however, AQP3 mRNA was absent in basal cell carcinoma, nevocellular nevus, or malignant melanoma. By immunohistochemistry, diffuse AQP3 expression was seen in all keratotic lesions including seborrheic keratosis, verruca vulgaris, molluscum contagiosum, solar keratosis, Bowen’s disease, and squamous cell carcinoma. Diffuse AQP3 expression was also present in all extramammary Paget’s disease. No AQP3 staining was obtained in basal cell carcinoma. Positive AQP3 staining was seen in sweat gland tumors including hidradenoma, eccrine poroma, and apocrine carcinoma. Among sebaceous tumors, AQP3 expressed diffusely in all sebaceous hyperplasia and sebaceous adenoma, but not in sebaceous carcinomas. Only focal AQP3 staining was seen in nevocellular nevus and no AQP3 staining in melanoma. Our findings indicate the function of AQP3 maintained in most skin tumors. AQP3 may be used for differential diagnosis in skin tumors.

SATB2 is a sensitive marker for colorectal adenocarcinomas. No study has investigated its diagnostic utility in metastatic Krukenberg tumors (MKTs) of the ovary. Here we performed immunohistochemical staining SATB2 in 70 MKTs of various origins (stomach 27, colorectum 13, appendix 20 including 19 metastatic adenocarcinomas ex goblet cell carcinoids [AdexGCC] and 1 conventional poorly differentiated carcinoma with signet ring cells, breast 5, bladder 3, lung 2) to assess its diagnostic utility. We also compared SATB2 with CDX2, CK7, CK20, chromogranin, and synaptophysin in MKTs of gastric origin (MKTs-stomach), those of colorectal origin (MKTs-colorectum) and those due to appendiceal AdexGCCs (MKT-AdexGCCs) for their sensitivity and specificity to distinguish these tumors. SATB2 staining was seen in 1/27 (4%) MKTs-stomach (40% cells), 7/13 (54%) MKTs-colorectum (mean: 17% cells, median: 7%, range: 2% to 60%), and 19/19 (100%) of MKT-AdexGCCs (mean: 97% cells, median: 100%, range: 80% to 100%) (P0.01 between any two). SATB2 staining was seen in 1/1 metastatic appendiceal poorly differentiated carcinoma with signet ring cells (5% cells), 1/3 MKTs of bladder origin (60% cells), 0/2 MKTs of pulmonary origin, and 1/5 MKTs of breast origin (10% cells). SATB2 staining was diffuse strong in MKT-AdexGCCs whereas in other MKTs it was focal and weak in the signet ring and nonsignet ring nonglandular cells and from focal weak to diffuse strong in well-formed glands. MKTs-stomach, MKTs-colorectum, and MKT-AdexGCCs showed no significant staining difference in CDX2 (100%, 100%, 100% cases, respectively; P=1.0), CK20 (96%, 100%, 100%, respectively; P=1.0), chromogranin (59%, 31%, 63%, respectively; P0.05) or synaptophysin (59%, 63%, 84%, respectively; P0.05) but they had significant difference in CK7 staining (93%, 8%, 42%, respectively; P0.05). Among these 6 markers, SATB2 is the best one to distinguish MKT-AdexGCCs from MKTs-stomach (100% sensitivity, 96% specificity) and MKTs-colorectum (100% sensitivity and 100% specificity if staining more than 75% tumor cells as the cutoff). In distinguishing MKTs-stomach from MKTs-colorectum, SATB2 is not as good as CK7 which is the best marker. Our results indicate that SATB2 is a highly sensitive marker (100% sensitivity) for metastatic MKT-AdexGCCs with high specificity (100% specificity when showing strong staining in at least 75% cells) among MKTs. SATB2 is a useful marker for determining the primary sites of MKTs of the ovary.

Background Immune checkpoint blockade targeting PD-1/PD-L1 has shown efficacy in several types of cancers. However, the correlation between PD-L1/PD-1 expression and the specific clinicopathological features in papillary thyroid carcinoma (PTC) has not been investigated. Methods We examined the immunohistochemical expression of PD-L1, PD-1, and BRAF V600E on whole-tissue sections from 126 cases of primary PTC more than 1 cm in size. The correlation between the PD-L1/PD-1 expression and the clinicopathological features was evaluated. Results PD-L1 was positively expressed in 53.2% PTCs, and its expression was positively correlated with rich tumor-infiltrating lymphocytes (TILs), background chronic lymphocytic thyroiditis (CLT), female gender, absence of psammoma bodies, and PD-1 expression. Among these parameters, rich TILs, female gender, and absence of psammoma bodies were independent factors affecting PD-L1 expression on the multivariate logistic regression analysis. PD-1 expression was detected in the TILs and was positively correlated with rich TILs, background CLT, and absence of stromal calcification. Lack of stromal calcification was an independent factor affecting PD-1 expression. Neither PD-L1 nor PD-1 expression showed significant correlation with BRAF V600E expression. Conclusions Our results show that the distinctive pathological features of PTCs, including TILs, background CLT, female gender, psammoma bodies, and stromal calcification, are useful parameters for predicting PD-L1 or PD-1 expression.

HER2 is an orphan receptor tyrosine kinase of the EGFR families and is considered to be a key tumor driver gene [1]. Breast cancer and gastric cancer with HER2 amplification can be effectively treated by its neutralizing antibody, Herceptin. In clinic, Immunohistochemistry (IHC) was used as the primary screening method to diagnose HER2 amplification [2]. However, recent evidence suggested that the frequently used rabbit HER2 antibody 4B5 cross reacted with another family member HER4 [3]. IHC staining with 4B5 also indicated that there was strong non-specific cytoplasmic and nuclear signals in normal gastric mucosal cells and some gastric cancer samples. Using a protein lysate array which covers 85% of the human proteome, we have confirmed that the 4B5 bound to HER4 and a nuclear protein ZSCAN18 besides HER2. The non-specific binding accounts for the unexpected cytoplasmic and nuclear staining of 4B5 of normal gastric epithelium. Finally, we have developed a novel mouse HER2 monoclonal antibody UMAB36 with similar sensitivity to 4B5 but only reacted to HER2 across the 17,000 proteins on the protein chip. In 129 breast cancer and 158 gastric cancer samples, UMAB36 showed 100% sensitivity and specificity comparing to the HER2 FISH reference results with no unspecific staining in the gastric mucosa layer. Therefore, UMAB36 could provide as an alternative highly specific IHC reagent for testing HER2 amplification in gastric cancer populations.

The mechanism of carcinogenesis of gastric cancer (GC) is still unclear now. This study aimed to explore the correlations among PD-L1, Epstein-Barr virus (EBV) infection, lymphocyte infiltration, HER2 expression, HER2 gene status, histology, and other clinicopathological factors in GC. A total of 44 GC patients with massive lymphocyte infiltration (GC-MLI) and 93 GC patients without massive lymphocyte infiltration were involved in this study. Immunohistochemical analysis was used to test the expression levels of PD-L1 and HER2. Fluorescence in situ hybridization was used on HER2-positive cases with a score of 2+ to test the HER2 gene status. EBV-encoded RNA was used to test for EBV infection. In univariate analysis, PD-L1 expression was significantly associated with GC-MLI (P

Background Recent research supports a significant role of immune checkpoint inhibitors in the treatment of solid tumors. However, relevant reports for programmed death-ligand 1 (PD-L1) and CD8+ tumor-infiltrating lymphocytes (TILs) in pulmonary neuroendocrine tumors (PNETs) have not been fully studied. Therefore, we investigated PNETs for the expression of PD-L1 and infiltration by CD8+ TILs as well as the prognostic value of both factors. Methods In total, 159 specimens of PNETs (35 TC, 2 AC, 28 LCNEC, 94 SCLC) were included in this study. Immunohistochemistry (IHC) was used to detect the expression of PD-L1 in these cases. Cases demonstrating ≥5% tumor cell expression or any expression (> 1%) of PD-L1 on immune cells were considered positive. CD8+ TILs both within stroma and tumor areas of invasive carcinoma were analyzed using whole-slide digital imaging. Manual regional annotation and machine cell counts were performed for each case. Results Positive expression of PD-L1 was observed in 72 cases (45.3%), including 9 cases (5.7%) with expression exclusively on tumor cells, 46 cases (28.9%) with expression exclusively on immune cells, and 17 cases (10.7%) with the expression on tumor cells and immune cells. PD-L1 expression was associated with necrosis (p

Background GATA-binding protein 3 (GATA3) has been identified as a sensitive marker for breast carcinoma but its sensitivity in primary genital extramammary Paget diseases (EMPDs) has not been well studied. Methods Here we investigated immunohistochemical expression of GATA3 in 72 primary genital EMPDs (35 from female, 37 from male; 45 with intraepithelial disease only, 26 with both intraepithelial disease and invasive adenocarcinoma including 14 also metastasis, 1 with metastatic adenocarcinoma only for study). We also compared GATA3 to gross cystic disease fluid protein 15 (GCDFP15) for their sensitivity. Results Positive GATA3 staining was seen in all 71 (100%) intraepithelial diseases, 25/26 (96%; female 10/10, male 15/16) invasive adenocarcinomas and 14/15 (93%; female 3/3, male 11/12) metastatic adenocarcinomas, respectively. Positive GCDFP15 staining was seen in 46/71 (65%; female 28/34 or 82%, male 18/37 or 49%) intraepithelial diseases, 20/26 (77%; female 9/10, male 11/16) invasive adenocarcinomas, and 12/15 (80%; female 2/3, male 10/12) metastatic adenocarcinomas, respectively (GATA3 versus GCDFP15: p

Immune checkpoint inhibitor therapies targeting PD-L1/PD-1 have been shown to be effective in treating several types of human cancer. In papillary thyroid carcinoma (PTC), little is known about the expression of PD-L1/PD-1 in the tumor microenvironment or its potential correlation with BRAF V600E mutation status. In this study, we examined the expression of PD-L1, PD-1, and BRAF V600E in PTC by immunohistochemistry and investigated the clinical significance of expression status. We studied the expression of PD-L1, PD-1, and BRAF V600E by immunohistochemical staining in 110 cases of PTC with a diameter > 1 cm. Cases with a background of chronic lymphocytic thyroiditis (CLT) were excluded, as differentiating lymphocytes in the context of CLT from tumor-infiltrating lymphocytes (TILs) is difficult. We classified PD-L1+/PD-1+ expression as type 1 (41%), PD-L1−/PD-1− as type 2 (17%), PD-L1+/PD-1− as type 3 (5%), and PD-L1−/PD-1+ as type 4 (37%). Significant correlations were found between expression of BRAF V600E and that of PD-L1 and PD-1. The positive correlation observed between expression of BRAF V600E and PD-L1/PD-1 suggests that immunotherapies targeting PD-L1/PD-1 might be effective for PTC patients with the BRAF V600E mutation, which are refractory to radioiodine therapy.

Nasal-type extranodal NK/T cell lymphoma (NK/TCL) is a rare malignancy that usually presents as a destructive midline lesion in the nasal region. The incidence of nasal-type extranodal NK/TCL has been reported to be much higher in Asia and South America than in North America and Europe. Its diagnosis mainly relies on histopathological and immunohistochemical examinations. Most patients demonstrate rapid disease progression and short survival. This report concerns a 37-year-old male with nasal-type extranodal NK/TCL showing severe facial disfigurement who was initially misdiagnosed as having Aspergillus infection. The report emphasizes the clinical manifestations and the importance of pathological diagnosis.

Xenotransplantation of human cancers into immunodeficient mice is a very useful approach for studying human tumor biology. However, the occasional occurrence of lymphomagenesis in some mice can spoil the model and must be investigated in detail. We found that a high percentage (32.5%, 26/80) of cancer patient-derived xenografts (PDXs) resembled lymphoma in NOD/SCID mice. Of the 26 xenografts, 23 were human-derived expressing human CD45 (hCD45+) and proved to be of the B-cell subtype (CD3-/CD20+) and they were all positive for Epstein - Barr virus (EBV). The remaining 3 xenografts proved to be mouse-derived for both hCD45- and negative amplification of a human gene. The most interesting finding is that gastric cancer had much higher rates (24/126, 19.0%) of lymphoma formation in the PDX model than did colorectal cancer (1/43, 2.3%). Statistical analysis revealed that cancer type and inflammation in the parent tumor are significantly associated with lymphomagenesis. Further validation discovered lymphomagenesis by inoculating only gastritis mucosa. Therefore, our findings suggest that it is necessary to take precautions when directly xenografting cancer tissues with remarkable baseline inflammation, such as gastric cancer into immunodeficient NOD/SCID strains. Further, the established xenograft models should be validated by both leukocyte markers and human gene signatures.

To investigate the clinicopathologic characteristics, prognosis and histologic origin of the mucinous tumor of the peritoneum.According to 2010 WHO classification of tumours of the digestive system, 34 cases diagnosed as "pseudomyxoma peritonei (PMP) " were reevaluated and divided into low grade and high grade. Immunohistochemistry was applied to investigate the expression of SATB2 and the histologic origin of the mucinous tumor of the peritoneum, using antibodies against SATB2, CK7, CK20 and CDX-2. The relationship between clinicopathologic characteristics and prognosis of the low grade and high grade tumors were analyzed.Twenty five patients had low grade mucinous tumors (two of them were no cell type), nine patients had high grade mucinous tumors. There was no significant difference between low grade and high grade mucinous tumors in age, sex, recurrence and organs involvement (P0.05). Thirty patients were followed up, the overall survival rates of patients with low grade and high grade mucinous tumors were 13/21 (61.9%) and 3/9, respectively. The median survival time was 74 and 24 months in low and high grade patients, and the difference was statistically significant (P=0.002).Immunohistochemistry showed the expression rates of CDX-2, CK20, and CK7 in totally 32 cases (excluding 2 cases of no cell type) were 30/32(93.8%), 31/32 (96.9%), and 3/16, respectively; the expression rates of CDX-2, CK20, and CK7 in 16 cases with distinct primary site were 15, 16, and 1, respectively; fifteen of 16 cases of tumors of unknown primary site were positive for CDX-2 and CK20, two of the them were positive for CK7. There was no difference in the expression of CDX-2, CK20 and CK7 between tumors with distinct primary site and tumors with unknown primary site (P0.05). The expression rate of SATB2 in the cases was 56.3% (18/32), excluding 2 cases of no cell type. There was no significant difference between low grade and high grade tumors in the expression of SATB2 [15/23(65.2%) vs 3/9, P=0.102], also SATB2 was not related to the prognosis of the tumor (P=0.786).The prognosis of the mucinous tumor of the peritoneum was significantly different between low grade and high grade according to WHO 2010 classification, and most mucinous tumor of the peritoneum originated from the appendix.