Danhua Shen

Peking University People's Hospital, Peping, Beijing, China

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Publications (15)25.21 Total impact

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    ABSTRACT: Endometrial carcinoma is one of the most common gynecological cancers and the incidence has been increasing. This study was to identify the relationship of estrogen receptor (ER), progestrone receptor (PR), P53 protein, Ki-67 and phosphatase and tensin homolog deleted on chromosome ten (PTEN) with endometrial carcinoma, the assessment of these biomarkers and their association with clinicopathological parameters was performed. A total of 198 cases of primary endometrial carcinoma were investigated for ER, PR, Ki-67, P53, and PTEN antigens by immunohistochemical methods. The association of these markers with age, menopause status, histological type, FIGO stage, grading, depth of invasion, lymph node involvement and serum tumor marker was examined. The percentages of Ki-67- and P53-negative endometrial tumors were significantly higher in ER-positive compared with ER-negative tumors (both P = 0.000). The same trend was evident with PR status. The percentage of PTEN-positive tumors was significantly higher in PR-positive compared with PR-negative tumors (P = 0.021), but was no difference in tumors with different ER status. There was no clear association between PTEN positivity and clinicopathological parameters except more relevance with endometrioid histotype (P = 0.013). There was a statistically significant difference in the distribution of the different combined biological factors examined in disease-free survival. ER and PR status were significant predictors with staging, grading and recurrence. P53 and Ki-67 expression were inversely correlated with both ER and PR expression and have more aggressive clinicopathological features. PTEN expression was inversely correlated with PR expression but not with ER expression. The combined type of ER+PR+P53-PTEN+ was in the majority in endometrial cancer and seemed to be related to better clinical outcome. The combination of ER-PR-P53+PTEN- represented the worst disease-free survival and was strongly associated with poorest survival rate.
    Chinese medical journal 04/2014; 127(8):1459-63. · 0.90 Impact Factor
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    ABSTRACT: The study aim was to explore the anatomy, histopathology, and molecular biological function of the fascias posterior to the interperitoneal colon and its mesocolon to provide information for improving complete mesocolic excision. To accomplish this aim, we performed intraoperative observations in 60 interperitoneal colon-cancer patients accepted for complete mesocolic excision and conducted local anatomy observations for five embalmed cadavers. An additional two embalmed child cadaver specimens were studied with large slices and paraffin sections. Ten of the 60 patients were examined with a lymph node tracer technique in vivo, while fresh specimens from these patients were assessed by histopathological examination and transwell cell migration assays in vitro. The anatomical and histopathological findings showed that the fascias posterior to the interperitoneal colon and its associated mesocolon were composed of two independent layers: the visceral and parietal fascias. These two fascias were primarily composed of collagen fibers, with the parietal fascia containing a small amount of muscle fiber. The in vivo test showed that the visceral fascia surrounded the colon and its associated mesocolon, including vessels and lymphatics, and that it had no lymphatic flow through it into the rear tissues. Moreover, the in vitro assays showed the visceral fascia was able to block tumor cell migration. Although many surgical scholars have known of the existence of fascia tissue posterior to the intraperitoneal colon, the detailed structure has been ignored and been unclear. As shown by our findings, the visceral and parietal fascias are truly formed structures that have not been previously reported. A thorough understanding of fascial structures and the function of the visceral fascia barrier in blocking tumor cells will facilitate surgeons when performing high-quality complete mesocolic excision procedures.
    Journal of Anatomy 05/2013; · 2.36 Impact Factor
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    ABSTRACT: BACKGROUND: To explore the potential application of placenta-specific PLAC1/Cancer Placenta (CP) 1 antigen for immunotherapy in CRC patients, further identification of the cytotoxic T lymphocyte epitopes from this antigen is necessary. METHODS: We assessed the protein expression of PLAC1/CP1 using a tissue chip and immunochemistry staining in CRC samples. Simultaneously, we predicted four PLAC1/CP1-derived HLA-A*0201-restricted peptides by using reverse immunology methods. Peptide-specific CD8(+) T cell responses were assessed by an IFN-γ release ELISPOT assay. Effector CD8(+) T cells lyse HLA-A*0201 CRC cell line SW620 was detected in a granzyme-B release ELISPOT cytotoxicity assay. RESULTS: Our results indicated that PLAC1/CP1 was highly expressed in 56.7 % (55/97) of adenocarcinomas. PLAC1/CP1 protein expression was associated with CRC tumor differentiation, the tumor/node/metastasis stage, and lymph node metastasis. Two of four peptides showed high affinities in an HLA-A2 binding assay. In 66.7 % (6/9) of peripheral blood mononuclear cells of CRC samples with PLAC1/CP1 protein-positive expression, these two peptides, PLAC1/CP1 p41-50 (FMLNNDVCV) and PLAC1/CP1 p69-77 (HAYQFTYRV), were immunogenic in the induction of peptide-specific CD8(+) T cell responses as assessed by an IFN-γ release ELISPOT assay. Furthermore, the generated effector CD8(+) T cells could specifically lyse the PLAC1/CP1 HLA-A*0201 CRC cell line SW620 in a granzyme-B release ELISPOT cytotoxicity assay. CONCLUSIONS: These results show that the PLAC1/CP1 antigen is a possible prognostic marker of CRC and that PLAC1/CP1 p41-50 and PLAC1/CP1 p69-77 are novel HLA-A*0201-restricted CD8(+) T cell epitopes and potential targets for peptide-based immunotherapy in CRC patients.
    Journal of Gastroenterology 04/2013; · 3.79 Impact Factor
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    ABSTRACT: We report the case of a 74-year-old woman with a primary mucinous borderline tumor of the fallopian tube coexisting with an ovarian mucinous borderline tumor. Data were obtained through histopathologic study of the excised surgical specimen. p53, estrogen receptor (ER) and PAX8 expression were evaluated by immunohistochemistry on the available right fallopian tube and ovary. Both the ovarian and fallopian tube borderline ovarian tumors were negative for p53, ER and PAX8. However, the staining pattern highlighted the transition from a normal ciliated cell to neoplastic epithelia in the fallopian tube fimbria. This is the first report to indicate that mucinous borderline tumors may arise from the ciliated cells at the fallopian tube fimbrial epithelia. ER and PAX8 are useful markers in identifying the transition and origination of these tumors.
    International journal of clinical and experimental pathology 01/2013; 6(5):962-5. · 2.24 Impact Factor
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    ABSTRACT: Objective: Estrogen receptor-α36 (ER-α36), a newly identified variant of ER-α, is predominantly membrane-based and mainly mediates nongenomic estrogen signaling. In this study, we investigated the expression of ER-α36 in human endometrial carcinoma tissues to understand the relationship between its expression and clinicopathological characteristics. Methods: ER-α36 expression was assessed by immunostaining in 73 endometrial carcinomas, 20 normal endometrial tissues, and 9 with atypical endometrial hyperplasia. Correlations between ER-α36 protein expression and clinicopathological characteristics were investigated. Results: The expression of ER-α36 in endometrial carcinoma tissues was significantly lower than in normal endometrial tissues and atypical hyperplasia (p < 0.01). ER-α36-negative tissues were significantly more likely than ER-α36-positive tumors to have tumor involvement of the cervix (p < 0.05). The disease-free survival rate of patients with ER-α36 expression was poorer than that of those who were negative for ER-α36 expression (p < 0.01). There was no significant relationship between ER-α36 expression and patient age, surgical staging, histological differentiation, myometrial invasion, lymph node metastasis, and pathological types (p > 0.05). Conclusions: ER-α36 may be an important biomarker for diagnosis, prognostication, and treatment choice in endometrial carcinoma.
    Gynecologic and Obstetric Investigation 12/2012; · 1.10 Impact Factor
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    ABSTRACT: Objective: To investigate the clinical characteristics of mirror syndrome. Methods: Retrospective analysis of cases with mirror syndrome. Data of clinical manifestations, laboratory examinations, placental morphology, treatment and prognosis of these patients were obtained and studied. Results: Five cases satisfying the inclusion criteria for mirror syndrome were identified from our hospital database. The incidence of the condition was 0.0154% in China. Mirror syndrome was associated with Rhesus isoimmunization, intrauterine parvovirus B19 infection, fetal neuroblastoma, fetal heart malformation and unknown cause respectively. Fetal symptoms were multi-hydrocele and fetal heart failure complicating fetal hydrops. All of the cases manifested maternal hydrops and hemodilution, the other most common symptoms included hypertension, proteinuria, hypoalbuminemia, anemia, thrombocytopenia and elevated uric acid levels. Fetal outcomes in this study were poor with a perinatal mortality rate of 100%. Placentomegaly was observed in most cases and placental morphology showed villous edema, increased intervillous fibrin deposition and one rare case of fetal adrenal neuroblastoma. Resolution of maternal symptoms was noted within 3-30 days after delivery. Conclusion: Mirror syndrome is associated with a substantially increased risk of fetal death and severe maternal complications. Early diagnosis of this condition during pregnancy is crucial for providing proper treatments and achieving better clinical outcomes.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 10/2012; · 1.36 Impact Factor
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    ABSTRACT: The aim of the present study was to investigate the expression of Ki-67, P53 and P63 in hydropic abortion and partial mole and to explore possible role of these three parameters in distinguishing partial mole from hydropic. The hydropic abortion (n = 13) and partial mole (n = 23) were retrieved from the files of 2002 to 2010 at the Department of Pathology, Peking University People's Hospital and Department of Pathology, Haidian Maternal and Child Health Hospita1. All cases had typical histological features and complete clinical information. All pathologic diagnoses were reviewed by two gynaecologic pathologists and had no conflict. All cases showed P57 negative, which can exclude the diagnosis of CHM. An immunochemical study of the expressions of Ki-67, P53 and P63 was performed. Microscopically, the pathologic characteristics of a HA include villous oedema with minimal to no cistern formation and mild trophoblastic hyperplasia. In contrast, the pathologic features of PHM were characterized by focal trophoblastic hyperplasia and a variable degree of hydropic swelling with central cistern formation. The Ki-67 expression was observed in the nuclear of cytotrophoblastic cell and intermediate trophoblasts population within placental tissue. The Ki-67 expression in HA is less than that in PHM. The p53 expression was observed in the nuclear of cytotrophoblastic cell and intermediate trophoblasts population within placental tissue. There was a significant difference between HA and PHM. Positive staining for P63 was localized in the nuclei of cytotrophoblastic cell population. No significant difference was observed in positive rate of p63 expression between HA and PHM. The high Ki-67 labeling index and over-expression of p53, detected by immunohistochemistry, could serve as useful adjuncts to conventional methods of diagnosis in distinguishing PHM from HA. Due to, however, the limited samples, it needs to expand the number of the cases to verify this conclusion.
    Wiener klinische Wochenschrift 01/2012; 124(5-6):184-7. · 0.81 Impact Factor
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    Yanru Hou, Yi Li, Danhua Shen, Heng Cui
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    ABSTRACT: Highlights ► The case is unique as the signet ring-like tumor cells in the ascites occur in primary peritoneal serous tumors. ► The tumor cells may have degenerated, which led to the formation of cytoplasmic vacuoles and resembled signet ring-like cells.
    Gynecologic Oncology Case Reports. 12/2011; 1(1):4–5.
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    ABSTRACT: Epithelioid angiosarcoma is a rare histopathologic variant of angiosarcoma characterized by an epithelioid morphology. This subset can histologically mimic non-vascular neoplasms and impose serious challenges in reaching a correct diagnosis, especially in the context of limited tissue sampling (e.g., needle core biopsy). To improve recognition of epithelioid angiosarcoma - and the spectrum of morphologic diversity associated with this rare variant - and to avoid a misdiagnosis, we describe the clinical, histopathologic, and immunohistochemical findings of cases of epithelioid angiosarcoma diagnosed at our institution. Seven cases of epithelioid angiosarcoma with appropriate pathologic material were identified from our archives. Immunohistochemistry was used to detect the expression of CD31, CD34, Factor VIII, cytokeratin, epithelial membrane antigen, vimentin, HMB45, CD1a, CD68, lysozyme, CD45, desmin, and smooth muscle actin in all cases. Follow-up information was obtained by reviewing medical records or by direct communication with family members. The lesions involved the bone (n = 4) and soft tissues (n = 3). Microscopically, all tumors had a predominantly diffuse growth pattern, with a focal nested architecture in 6 cases, which closely mimicked metastatic carcinoma. The initial biopsy was performed in 2 of 6 patients and revealed the presence of a malignant neoplasm suggestive of metastatic carcinoma. Immunohistochemically, the epithelioid endothelial cells usually showed strong reactivity for CD31 (7/7), variable or focal positive staining for CD34 (5/7), Factor VIII (4/7), cytokeratin (6/7), epithelial membrane antigen (2/7), vimentin (7/7), and CD68 (3/7). In contrast, they were negative for CD1a, HMB45, lysozyme, CD45, desmin, and smooth muscle actin. Three patients died of disease within one year of the diagnosis, 2 patients developed local recurrence or metastases, and another 2 were disease-free at this writing. With any unusual epithelioid neoplasm displaying some or all of the morphologic features described above, epithelioid angiosarcoma should be included in the differential diagnosis. In such an instance, endothelial markers should be incorporated in the immunohistochemical analysis to avoid misdiagnosis, particularly with limited sampling.
    Tumori. 09/2011; 97(5):585-9.
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    ABSTRACT: The main objective of this study was to refine more precisely the gene expression patterns used to distinguish serous from endometrioid endometrial carcinoma. A low-density cDNA microarray containing 492 genes was designed and constructed. The gene expression profiles of 32 endometrioid and 5 serous endometrial cancer tissue samples were compared. The expression of 5 differentially expressed genes: NDC80, BUB1, FUT8, ANXA4 and BBC3 in endometrioid and serous adenocarcinoma samples was further evaluated by quantitative real-time PCR and immunohistochemistry. Unsupervised cluster analysis revealed that the 5 serous adenocarcinomas clustered together. These were separated from the endometrioid adenocarcinomas which were further sorted into 3 additional clusters. A comparative analysis indicated that there was a significant difference in FIGO stage with no significant difference in depth of myometrial invasion among the 4 clusters. The FIGO ternary grading system could not distinctly separate the 3 clusters of endometrioid adenocarcinomas, but a binary grading system was able to do so. Using a supervised analysis, we have identified 46 genes exhibiting >2-fold differences that can be used to statistically differentiate serous adenocarcinomas from endometrioid adenocarcinomas. The directions of gene and protein expression change of five differentially expressed genes estimated by real-time PCR and immunohistochemistry are consistent with those estimated from microarray. Serous adenocarcinoma exhibits distinct gene expression profiles, compared with those of endometrioid adenocarcinoma. These differences make it feasible to validate microarray data by immunohistochemistry, and they will ultimately allow us to identify tumors according to their immunohistochemical phenotype. The accuracy of classifying endometrial tumors using a system based on their gene expression patterns is much higher than the accuracy of the FIGO grading system. Thus, this gene expression pattern-based system may prove to be crucial in developing novel treatment strategies for endometrial cancers at the molecular level in future.
    Experimental and Molecular Pathology 04/2011; 91(1):373-84. · 2.13 Impact Factor
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    ABSTRACT: Gastric cancer (GC) is the one of the most common types of cancer in Asia. To better understand the molecular mechanisms underlying GC, and to seek new markers of tumor progression, we used a proteomics strategy to analyze the protein expression patterns in matched pairs of GC tissue and normal gastric mucosa of 8 GC patients. Comparative proteomic analysis, using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), revealed that 32 protein spots showed a >2-fold difference in intensity between tumor and normal tissues. Twenty-six proteins were up-regulated and 6 proteins were down-regulated in tumor tissue compared to control. Western blot analysis confirmed differential expression for 9 proteins, including AGR2, ENO1, GDI2, GRP78, GRP94, PPIA, PRDX1, PTEN and VDAC1. Immunohistochemical staining of a tissue microarray, derived from 145 GC patients, with antibodies for each of the 9 proteins demonstrated a significant association between the level of protein immunostaining and the clinical features of the disease in the donor. The identified proteins were functionally classified using bioinformatics methods, showing that the 9 proteins identified were related to BCL2, BAX, ERBB2 and CASP3 proteins and involved in the process of apoptosis. These proteomic data provide potentially valuable insights into both the biology of GC and the identity of biomarkers for tumor progression. We propose ENO1, GRP78, GRP94, PPIA, PRDX1 and PTEN as potential GC biomarkers.
    International Journal of Oncology 02/2011; 38(2):375-83. · 2.66 Impact Factor
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    ABSTRACT: To investigate whether the molecular classification of endometrial cancer based on gene expression profiles can predict the biological behavior of the tumors and inform prognosis. An array containing 492 genes was used to generate gene expression profiles from 35 tumor samples. A hierarchical cluster algorithm was used to compare gene expression patterns among the tumor samples. A cluster analysis revealed 3 distinct tumor clusters. A comparative analysis of tumor type, grade, FIGO stage, and depth of myometrial invasion revealed significant differences in grade and stage among the clusters, which appear to group tumors with specific clinical behaviors. Moreover, the cluster analysis initially revealed 2 clusters of differentially expressed genes. One contained 38 genes that were upregulated in most samples of the cluster representing the most advanced disease, and the other contained 27 genes that were upregulated in most samples of the cluster representing the least advanced disease. Molecular classification of endometrial cancer based on gene expression profiles obtained by designing specialized microarrays indicated a marked correspondence with the histologic features and clinical behavior of endometrial cancer tumors.
    International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 08/2010; 110(2):125-9. · 1.41 Impact Factor
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    ABSTRACT: To search for potential protein markers of colorectal cancer (CRC), the changes in protein expression levels between microdissected tumor cells and normal mucosa epithelia were analyzed by an acetylation stable isotopic labeling method coupled with linear quadrupole ion trap fourier transform mass spectrometry (LTQ-FTMS). In total, 137 proteins were up-regulated or down-regulated significantly in cancer by at least two-fold. Based on gene ontology analysis, the largest part of differential proteins were unknown for both subcellular localization and biological process. In particular, the significant up-regulation of transgelin-2 (TAGLN2) in CRC was validated by Western blot analysis and further evaluated by immunohistochemistry in paired tumor and normal mucosa samples from 120 consecutive CRC patients, 20 adenomas, and eight synchronous hepatic metastases of CRC. TAGLN2 expression was frequently observed in cancer cells, precancerous lesions, and hepatic metastases, whereas in normal epithelia expression was rarely observed. The overexpression of TAGLN2 was associated with lymph node and distant metastasis, advanced clinical stage (P < 0.001), and shorter overall survival in CRCs. Cox regression analysis indicated that high tumor-TAGLN2 expression represents an independent prognostic factor. Consequently, over-expression of TAGLN2 may serve as a new biomarker for predicting progression and prognosis of CRC.
    Cancer Science 11/2009; 101(2):523-9. · 3.48 Impact Factor
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    ABSTRACT: The aim of the study was to analyze the expression of Cdx2 and nuclear PTEN in relation to clinicopathological features of gastric cancer tissue biopsies in order to determine the value of a combined analysis of Cdx2 and nuclear PTEN expression in distinguishing histological types and prognosis of gastric cancers. The expression of Cdx2 and nuclear PTEN was studied using immunohistochemistry of paraffin-embedded tumor specimens from 99 patients who underwent radical D2 gastrectomy between 1999 and 2001. Cdx2 and nuclear PTEN expression were detected in 39.6% (36 of 91) and 70.3% (64 of 91) of gastric cancer cases, respectively. There was a negative correlation between Cdx2 expression and Lauren classification (p=0.032), and between nuclear PTEN expression and lymph node metastasis (p=0.049). Patients with Cdx2-positive, or nuclear PTEN-positive expression had higher survival rates than those with Cdx2-negative or nuclear PTEN-negative expression (p<0.001 and p=0.003, respectively). Co-expression of Cdx2 and nuclear PTEN showed significantly lower levels in diffuse- or mixed-type cancers than in intestinal-type cancers (p=0.005). Multivariate analysis revealed that Cdx2 expression was an independent prognostic indicator of gastric cancer (p=0.014). These data suggest that combined analysis of Cdx2 and nuclear PTEN expression can have significant value in distinguishing histological types of gastric cancer and assessing prognosis in patients with gastric cancer.
    Apmis 12/2007; 115(12):1383-90. · 2.07 Impact Factor
  • Chinese medical journal 02/2002; 115(1):138-40. · 0.90 Impact Factor