2012 Vol. 3, No. 1

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Original Contributions
Abstract:
  Objective  To investigate the expression and its significance of Cyclin D1 in invasive lobular carcinoma (ILC) of the breast.  Methods  The specimens from 75 cases of ILC were detected using immunohistochemical method.  Results  Of these 75 cases, Cyclin D1 was positive on the nucleus in 70 cases (93.33%), among which 41 (54.67%) showed strong diffuse staining (3 +, 6-7 points), and 21 (28%) were moderately positive (2 +, 4-5 points), and 8 (10.67%) were weak positive (1 +, 2-3 points). Only 5 (6.67%) cases showed negative results (0-1 points). The positive expression of Cyclin D1 showed no significant differences among patients in terms of age (> 50 years), maximum tumor diameter (> 2cm), lymph node metastasis, involvement of papillary interstitial tissue and the large duct beneath it, existence of estrogen and progesterone receptors, and the possible mutation of P53. However, an inverse correlation was found between the degrees of the positive staining of Cyclin D1 and the lymph node metastasis (P < 0.05).  Conclusion  Cyclin D1 is overexpressed in ILC, suggesting that there may be certain genetic abnormalities.
Abstract:
  Objective  To determine the effect of laminin (LN) on the intrinsic chemoresistance of pancreatic cancer and whether such effect is mediated by LN-induced focal adhesion kinase (FAK) phosphorylation and subsequent downstream signal pathway.  Methods  The effect of LN on gemcitabine (Gem) -induced cytotoxicity and apoptosis in pancreatic cancer cell line AsPC-1 cells were determined by MTT assay, clonogenic assay and apoptosis analysis. The effect of LN on the expression and phosphorylation of FAK, Akt, and ERK1/2 were detected by Western blotting. The changes in the effects of LN in AsPC-1 cells were explored by FAK phosphorylation inhibition through focal adhesion kinase-related non-kinase (FRNK) overexpression or specific FAK phosphorylation inhibitor PF-573, 228.  Results  LN decreased Gem-induced cytotoxicity and apoptosis in AsPC-1 cells. After Gem treatment for 72 h, the viability was 57.71%±6.08% and the colony number was 55.33±5.01 on LN, while the viability and the colony number on plastic were 36.65%±4.14% and 31.43±4.62, respectively (both P < 0.05). The Annexin V positivity of AsPC-1 cells on LN (41.00%±5.46%) was significantly lower than that on plastic (55.70%±3.44%) (P < 0.05). Moreover, LN induced FAK and Akt phosphorylation in a time-dependent manner and increased the levels of survivin and pBad (pS136). Specific inhibition of LN-induced FAK phosphorylation by either FRNK overexpression or PF-573, 228 suppressed the effect of LN on AsPC-1 cells. PF-573, 228 increased Gem-induced apoptosis in AsPC-1 cells from 26.77%±0.49% to 38.53%±2.83% on LN (P < 0.05).  Conclusions  LN contributes to the increased intrinsic chemoresistance of pancreatic cancer cell to Gem, which may be achieved through the regulation of FAK, Akt, and Bad phosphorylation and survivin expression. Targeted FAK inhibitors may be a promising way to enhance chemosensitivity in pancreatic cancer.
Abstract:
  Objective  To investigate the changes of HER2/neu gene in pancreatic and gastric adenocarcinoma in Chinese patients and to evaluate its roles in targeted gene therapy.  Methods  The expression of HER2/neu protein was detected using immunohistochemistry, while gene amplifications of HER2/neu were assessed using multi-color fluorescence in situ hybridization (FISH). The samples were paraffin embedded and 10% formalin fixed. They included 81 cases of pancreatic ductal adenocarcinomas with adjacent non-neoplastic pancreatic tissues and 100 cases of gastric adenocarcinomas with adjacent non-neoplastic gastric tisssues.  Results  Immunohistochemical tests showed that the positive rate of HER2/neu in pancreatic ductal adenocarcinomas and gastric adenocarcinomas was 11.1% (9/81) and 13% (13/100), respectively. FISH showed that HER2/neu gene amplification was detected in 18.5% (15/81) of pancreatic adenocarcinoma cases 11% (11/100) of gastric adenocarcinoma (including all 6 HER2/neu 3 + cases). HER2/neu protein expression and gene amplification were not found in adjacent normal tissues in both arms. Among the pancreatic adenocarcinoma cases, HER2/neu gene amplification was positively correlated with lymphoma metastasis (P=0.001).  Conclusions  Protein expression is not relevant with gene amplification of HER2/neu in pancreatic cancer. HER2/neu gene amplification may be the major reason for its protein overexpression in gastric adenocarcinoma. HER2/neu gene expression may play an important role in the carcinogenesis of pancreatic and gastric adenocarcinoma. Evaluation of the status of HER2/neu may be helpful to achieve the targeted therapy of pancreatic and gastric adenocarcinoma.
Abstract:
  Objective  To explore the effects of Let-7a and miR-96 molecules on inhibition K-RAS in pancreatic cancer.  Methods  The levels of K-RAS mRNA and protein were detected in 9 pancreatic cancer cell lines, and the abundance of Let-7a and miR-96 in 7 of these 9 cell lines were determined to analyze the relation between the levels of Let-7a or miR-96 and K-RAS protein expression. Then, the levels of Let-7a or miR-96 was increased in PANC-1 cell line by transfection to observe K-RAS protein change.  Results  A high level of K-RAS mRNA was observed in 9 pancreatic cancer cell lines, and K-RAS protein was also at a higher level than normal ones. But Let-7a and miR-96 maintained were at a lower level in pancreatic cancer cell lines. An increase of Let-7a or miR-96 decreased the K-RAS protein expression in PANC-1 cell line.  Conclusion  Compared to normal condition, the levels of Let-7a and miR-96 decrease in pancreatic cancer, leading to the attenuation of inhibition to K-RAS, which contributes to pancreatic cancer formation and progression.
Abstract:
  Objective  To investigate the clinical and pathological features of pulmonary intravascular lymphoma (IVL).  Methods  The clinical, radiographic, and pathological features of five cases of pulmonary IVL diagnosed by lung biopsy from March 2008 to June 2011 were retrospectively analyzed, and similar cases reported in English literatures were reviewed.  Results  These 5 patients (3 males and 2 females) aged 36 to 59 years, with a median age of 45 years. The chief complaints included fever (5/5), weight loss (5/5), cough (4/5), fatigue (3/5), and dyspnea (2/5). Pulmonary function tests mainly showed some degree of decreased diffusing capacity. All the five cases had high serum lactate dehydrogenase (range:316-1025 U/L). Chest CT showed diffuse ground-glass opacity (n=3), bilateral multiple nodular density with subpleural wedgeshaped density and thickening of bronchial wall (n=1), and consolidations in the right lower lobe (n=1). On histopathology, single or clustered lymphoma cells were seen within the lumens of capillaries of the alveolar septum, with the alveolar structure remained; the lesion was small and could not be easily identified. Pulmonary infarction caused by tumor thrombus was identified in one case. Immunophenotyping showed B cell lineage in 3 cases and T cell lineage in 2 cases. During the follow-up period (range:0.67-6 months; mean:3.17 months), 3 patients with B cell pulmonary IVL received R-CHOP chemotherapy and their diseases were improved and remained stable. One patient with T cell pulmonary IVL received CHOP chemotherapy but died due to gastrointestinal bleeding and respiratory failure 20 days after diagnosis. One patient with T cell pulmonary IVL was lost to follow-up.  Conclusions  Pulmonary IVL is a rare malignant disease that mainly seen in the elderly. Its clinical symptoms are not specific. Chest CT usually reveals diffuse interstitial changes, which should be carefully differentiated from interstitial pneumonia, pulmonary infection, and lung metastatic cancer. It can be pathologically diagnosed through transbronchial lung biopsy or surgical lung biopsy.
Abstract:
  Objective  To study the application of DNA image cytometry (DNA-ICM) in the diagnosis of pleural effusion.  Methods  DNA-ICM was applied for the determination of DNA levels in the cast-off cells from pleural effusion in 50 patients. Meanwhile, using the cytological test results as the standard, we analyzed the optimal thresholds of this technology in diagnosing the positive cases.  Results  Compared with exfoliative cytology examination, DNA-ICM had a sensitivity of 87.5% and a specificity of 100% in the diagnosis, with a threshold of 1 cell when the DNA index ≥ 2.5.  Conclusion  DNA-ICM can be promising in the diagnosis of pleural effusion, whereas its thresholds require further investigations.
Abstract:
  Objective  To study the clinicopathologic features and diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma of the thymus.  Methods  The clinical, pathologic, immunohistochemical and polymerase chain reaction (PCR) findings of two patients (one 57-year-old Chinese Han man and one 53-year-old Chinese Han woman) with thymic MALT lymphoma were retrospectively analyzed.  Results  Pre-operative computed tomography (CT) and magnetic resonance imaging (MRI) images and gross examination showed well-demarcated masses with multilocular cysts. Microscopy showed that the centrocyte-like lymphocytes formed broad, pale-staining bands and sheets, with frequent presence of epithelium-lined cysts and consistent plasma cell differentiation around small vessels. The dilated Hassall's corpuscle with eosinophilic material was observed. The lymphoepithelial lesions and reactive lymphoid follicle hyperplasia were common. Many small nodules, full of the lymphoma cells, located in the adipose tissue. The tumor cells were immunoreactive for CD20, CD79α, and Bcl-2. Immunostaining for AE1/AE3 highlighted the Hassall's corpuscles and epithelium lining the cysts. PCR for immunoglobulin heavy chain variable region (IgHV) rearrangements showed distinct bands indicating monoclonality in both two cases. No recurrence or metastasis was noted 27 and 6 months after surgery.  Conclusions  Thymus MALT lymphoma is rare, and may represent a distinct subgroup of MALT lymphoma characterized by apparent predilection for Asians. It has a strong association with autoimmune disease, frequent presence of cysts, consistent plasma cell differentiation, and consistent lack of API2-MALT1 gene fusion. Surgery is the treatment of choice, usually resulting in good outcome.
Abstract:
  Objective  To investigate the clinicopathological features of solitary desmoplastic fibroma of the bone (DF).  Methods  Totally 4 cases of DF were confirmed in our hospital from October 2004 to July 2008. Their clinical manifestations as well as the pathologic, morphologic, and immunohistochemical findings were summarized, and relevelant literature was reviewed.  Results  DF was composed of spindle cells (fibroblasts/myofibroblasts) in a background of numerous thick and wavy collagen fibers of ovoid nuclei dispersed within a collagenous fibers. No mitotic figures, hypercellularity, or pleomorphism was observed.  Conclusion  DF is a rare benign lesion and can be progressive, invasive, and sometimes recurrent.
Abstract:
  Objective  To investigate the clinicopathological features, immunophenotype, and differential diagnosis of intravenous leiomyomatosis (IVL).  Methods  Clinical manifestations, morphologic features, and immunohistochemical staining results from 34 patients with IVL were retrospectively analyzed.  Results  Patients were aged 24 to 61 years (mean 44.8 years), with the clinical manifestations included edema of low extremity, abdominal distention, hypermenorrhea, and other pelvic discomfort. In patients whose inferior vena cava and heart were also involved, the symptoms also included chest tightness, palpitation, and dyspnea. The morphologic changes were observed in uterine (n=14), pelvic veins (n=6), and inferior vena cava (IVC) (n=14); in 9 patients, tumors extended into right heart chamber through IVC. Microscopically, the tumors were composed of spindle-shaped cells with rare mitotic figure. The tumors were positive for SMA, ER, PR, and Desmin and negative for CD10 and HMB45. CD34 was positive in 4 patients and negative in the remaining patients. Ki-67 index ranged 0.3% -2.7%.  Conclusion  IVL is a rare disease among women of child-bearing age. It can be histologically begign but biologically malignant, with specific morphologic manifestations and immunohistochemical features.
Abstract:
  Objective  To observe the clinicopathological features of intestinal Behcet syndrome (BS).  Methods  The ileocolonic resections obtained from two patients with intestinal BS in Peking Union Medical College Hospital were reviewed with naked eyes and microscope. Their clinical features were also summarized.  Result  The common clinicopathological findings included:met the internationally recognized BS diagnostic criteria; ileocolonic resection was performed due to refractory intestinal bleeding; the intestinal ulcers, located within the ileocecal junction, were multifocal, perpendicular to the long axis of the intestine, and with adjacent mucosa became swollen; non-necrotizing vasculitis beneath the ulcers was found under microscope.  Conclusion  BS may be diagnosed based on its typical clinicopathological findings after other diseases are carefully excluded.
Abstract:
  Objective  To explore the clinicopathologic features, diagnostic criteria, and prognostic factors of villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix.  Methods  We retrospectively analyzed the clinical and pathological data of 10 VGPA patients including age, clinical stage, surgical procedure, outcome, macroscopic features, tumor size, horizontal spread and depth of endophytic tumor, nuclear atypicality, mitotic count, lymph capillary space invasion, and lymph node metastasis.  Results  The median age was 39 years. Eight patients were at stage FIGO Ib1, one at stage IIa, and one at stage Ia1. All patients who had undergone hysterectomy and lymphadenectomy were alive, one patient experienced recurrence, and one patient was lost to the follow-up. Macroscopically, 5 cases showed exophytic polypoid or florid lesions with the diameter ranged between 5-25 mm, 3 cases showed microvillous rough regions with area ranged between 25 mm×14 mm-35 mm×20 mm, and the recurrent case showed an ulcerative type of mass with the diameter of 25 mm. Horizontal spread and depth of endophytic tumor ranged between 5 -26 mm and between 2 -12 mm, respectively; the invasion of posterior fornix of vagina was observed in one case. All the non-recurrent cases showed mild to moderate cytologic atypia, while the recurrent one showed severe cytologic atypia. The mean mitotic count was 48/10 HPF. Cervical intraepithelial neoplasia (CIN) Ⅲ and/or acute coronary ischemia syndrome (ACIS) or a mixture of the two were found in 9 cases, 2 of which were simultaneously in association with welldifferentiated adenocarcinoma. Occasional lymph capillary space invasion was present in one case. None had corpus infiltration, bulky lymph node metastases, or ovary metastasis.  Conclusions  VGPA usually has a favorable prognosis. Predictors of a poor outcome include tumor infiltration of outer one-third cervical wall, corpus infiltration, vascular invasion, and positive lymph nodes; meanwhile, severe cytologic atypia and/or any other more aggressive malignant tumor can also play a role.
Abstract:
  Objective  To discuss the clinicopathological characteristics of hapatocellular dysplastic nodules.  Methods  Totally 12 cases of hepatocellular dysplastic nodules were collected and their clinical and pathological features were reviewed.  Results  Hepatocellular dysplastic nodules were shown as nodules on gross examination. On microscopic examination, they showed increased cell density as well as nucleus/cytoplasm ratio. Structural atypia and unpaired arteries were also found. In 2 cases there were foci of early hepatocellular carcinoma in dysplastic nodules. During the follow-up, 7 patients lived without tumors, and 1 patient developed hepatocellular carcinoma after 48 months.  Conclusion  Hepatocellular dysplastic nodules have typical clinicopathology and can be regarded as a precursor of hapatocellular carcinoma.
Abstract:
  Objective  To investigate the clinicopathological characteristics of poorly differentiated thyroid carcinoma (PDTC).  Methods  The clinical and pathological features as well as the imaging findings of 12 cases of PDTC were retrospectively reviewed.  Results  The 12 patients, 1 man and 11 women, with an average age of 53.6 years, presented with painless mass at the anterior neck. Grossly, the tumor had a nodular appearance. Histologically, the predominantly insular pattern was found in 4 tumors, the trabecular architecture in 5 tumors, and the solid flake architecture in 3 tumors. Immunohistochemically, TTF1 was positive in 11 cases. Thyroglobulin expression was noted in 10 cases. P53 immunostaining showed diffuse positivity in 4 cases and focal positivity in 3 cases. The Ki67 proliferative index ranged from 3% to 25%. Two patients died of the tumor progression 4 and 7.5 years after the surgery, respectively.  Conclusion  PDTC is a rare disease with clinicopathological characteristics intermediate between follicular/papillary and anaplastic carcinomas.
Abstract:
  Objective  To explore the clinicopathological features of primary peritoneal and primary ovarian serous papillary carcinoma in Chinese patients.  Methods  The clinical specimens were obtained from 10 patients who were confirmed to be with primary peritoneal serous papillary carcinoma (PPSPC) and from 20 otherwise-matched patients with ovarian serous papillary cancer (OSPC). The clinicopathological features of these PPSPC and OSPC cases were observed. The levels of estrogen receptors (ER), progesterone receptors (PR), human epidermalgrowth factor receptor 2 (HER2)/neu and P53 protein were detected using immuno-histochemical techniques. The status of HER2 gene was evaluated by fluorescence in situ hybridization (FISH) using PathVysionTM kit.  Results  The mean onset age was 8.3 years older among PPSPC patients than in OSPC patients (P=0.045). The proportion of poorly differentiated serous cancer was 60% among the PPSPC patients and 20% among the OSPC patients (P=0.045). Positive immunostaining for ER and PR was significantly less in PPSPC (60% and 10%, respectively) than OSPC (95% and 50%; P=0.031 and P=0.032, respectively). Positive expression of P53 was found in 40% of the PPSPC patients and 85% of the OSPC patients (P=0.045). HER2/neu was faint/barely perceptible membrane staining (1 +) in 10% of the PPSPC patients versus 15% of the OSPC patients. In addition, HER2 amplification was not found in either group.  Conclusions  PPSPC and OSPC share some clinicohistological features; however, compared with OSPC, PPSPC is more common in older women, with relatively poorer differentiation, stronger potential of invasion, lower ER/PR expression, lower P53 protein expression, and poorer outcomes.
Abstract:
  Objective  To explore the pathological manifestations of primary hepatic angiosarcoma and review the literature.  Methods  We retrospectively analyzed the pathological and clinical data of three cases of primary hepatic angiosarcoma, which were confirmed and treated in the Department of Pathology of Peking Union Medical College Hospital from 2001 to 2010.  Results  All these three cases showed no specific clinical manifestations and imaging results. Pathologically, there were varies of microscopic patterns such as hemangioma-like and epithelioid hemangioendothelioma-like apperieaces; however, specific pathological diagnostic features of angiosarcoma still existed in all three cases.  Conclusions  Primary hepatic angiosarcoma is a rare malignant tumor. The combined application of history-taking, symptom observation, imaging, and liver biopsy is important for the diagnosis of primary hepatic angiosarcoma.
Abstract:
  Objective  To explore the clinical features of cardiac amyloidosis (CA).  Methods  The clinical data of 17 CA patients who were diagnosed in our hospital from September 2006 to April 2010 were retrospectively analyzed.  Results  Of these 17 patients, 14 (82.4%) were over 40 years old, and the ratio of male to female was 1:1. Sixteen patients (94%) had two or more systems involved, and 9 patients (52.9%) had three or more systems involved. Patients were manifested as fatigue (41%) and/or skin petechia/ecchymosis. In the circulation system, seven patients (41.2%) showed a trend of hypotension, and echocardiography showed 14 patients (82.4%) had thickened ventricular walls[(14.6±2.27) mm]and interventricular septal thickness/left ventricular wall thickness >1.1 mm. Fourteen patients (82.4%) had impaired diastolic function of ventriculus sinister. Thirteen patients (76.5%) had increased echogenicity of the myocardium with a granular appearance. Fourteen patients (82.4%) had abnormal electrocardiogram findings. Eight patients (47%) had gastrointestinal systems, which included glossal hypertrophy (11.7%) and enlargement of the liver (17.6%). Seven patients (41.2%) showed renal insufficiency. Immunofixation electrophoresis of blood and urine detected monoclonal light chain in 52.9% of patients (λ light chain, n=8; κ light chain, n=1). One patient (5.9%) experienced nervous symptom.  Conclusion  CA can affect multiple systems, with heart, gastrointestinal system, and kidney as the most commonly involved target organs.
Abstract:
  Objective  To summarize our experiences in the pathologic diagnosis of rare pancreatic lesions.  Methods  The clinicopathological data of patients with rare pancreatic lesions which were confirmed in our department from 2000 to 2011 were retrospectively analyzed. Relevant literature retrieved from PubMed was reviewed.  Results  A total of 6 cases of rare pancreatic lesions were identified, which included myxoglobulosis (n=1), serous cystadenoma associated with ductal adenocarcinoma (n=1), acinar cell cystadenoma (n=1), intermediate mucous cystadenoma associated with mucoid leiomyosarcoma (n=1), osteoclast-like giant cell tumor (n=1) and ganglioneuroma (n=1). Few or no relevant literature was reported in PubMed database.  Conclusion  Special attention should be paid to these rare pancreatic lesions in clinical practice.
Abstract:
  Objective  To explore the effect of RNA interference (RNAi) plasmid on proliferation, apoptosis of status of Panc-1 cells by silencing oncogene AKT2, and investigate its possible mechanism.  Methods  Pancreatic cancer cell line Panc-1 was applied to constructe the RNAi plasmid-targeting oncogene AKT2 and to transfect cells transiently and stably. The proliferation status was determined using CCK-8 method and soft agar colone formation test. The apotosis status of the cancer cells in vitro was determined using Heochst and Annexin V-FITC/PI methods. The protein level of AKT2 and caspase-3 kinase were detected using Western blotting. Finally, we evaluate the in vivo effect of the recombinant plamids on Panc-1 cells.  Results  By silencing the oncogenes AKT2, RNAi plasmid effectively down-regulate the mRNA and protein levels of of AKT2 in Panc-1 cells reduced cell proliferation and colony formation of Panc-1 cells, induced apoptosis in Panc-1 cells, increased the protein level of caspase-3 protein, and inhibited tumor growth in vivo.  Conclusions  RNAi can inhibit the expression of oncogene AKT2 and therefore effectively inhibit the growth of pancreatic cancer cells and promote their apoptosis. Gene therapy targeting AKT2 may be a promising target for pancreatic cancer.
Abstract:
  Objective  To compare the blood loss between vaginal delivery and cesarean section in women at low-risk for postpartum hemorrhage, and to explore the risk factors of postpartum hemorrhage.  Method  The clinical data of nulliparous women who delivered in Peking Union Medical College Hospital from November 2008 to October 2009 were retrospectively analyzed. Women at high risk for postpartum hemorrhage (including placenta previa, placental abruption, and severe preeclampsia) were excluded. Pre-and post-delivery hematocrit (HCT) and hemoglobin (HGB) were recorded and compared between the vaginal delivery group and cesarean section group. The risk factors associated with postpartum hemorrhage were analyzed.  Result  After the delivery, the median decrease of HGB and HCT was-3 g/L (-10 g/L--3 g/L) and-1% (-3.1%--1.1%), respectively, in the elective cesarean section group, and was-8 g/L (-17 g/L-0 g/L) and-2.8% (-5.4%-0.1%) in the vaginal delivery group (both P < 0.05). The median decrease of HGB and HCT was-2.0 g/L (-12.7 g/L -4 g/L) and-1.0% (-3.98% -1.4%) in the no-episiotomy vaginal delivery group, which was not significantly different from that in the cesarean section group. Forceps, episiotomy, and postpartum curettage were risk factors for postpartum hemorrhage in vaginal delivery group.  Conclusions  For pregnant women at low risk for postpartum hemorrhage, blood loss during Cesarean section is larger than in vaginal delivery. Forceps, episiotomy, and postpartum curettage are risk factors for postpartum hemorrhage in vaginal delivery group.
2012, 3(1): 1-2. doi: 10.3969/j.issn.1674-9081.2012.01.001
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2012, 3(1): 3-4. doi: 10.3969/j.issn.1674-9081.2012.01.002
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2012, 3(1): 5-7. doi: 10.3969/j.issn.1674-9081.2012.01.003
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2012, 3(1): 113-116. doi: 10.3969/j.issn.1674-9081.2012.01.023
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2012, 3(1): 117-119. doi: 10.3969/j.issn.1674-9081.2012.01.024
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2012, 3(1): 120-123. doi: 10.3969/j.issn.1674-9081.2012.01.025
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