Clinicopathologic characteristics of fibrous mass-forming chronic pancreatitis / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate clinicopathological features of fibrous mass-forming chronic pancreatitis (FMCP), to compare clinicopathological and immunohistochemical characteristics between autoimmune pancreatitis (AIP) and fibrous mass-forming non-autoimmune pancreatitis (nAIP) and to provide evidence for pathological diagnosis, differential diagnosis and clinical treatment strategy.</p><p><b>METHODS</b>Clinicopathological features were analyzed in 81 cases of FMCP. Infiltrating IgG4(+) plasmacytes were counted by immunohistochemical staining.</p><p><b>RESULTS</b>Among 81 cases of FMCP, 20 cases were diagnosed as AIP and 61 cases were interpreted as nAIP. AIP was more common in males over 50 years, whereas nAIP was seen in much younger patients (P = 0.001). The amount of inflammatory cells in the stroma of AIPs was remarkable higher than that in nAIPs (P = 0.002). The incidence of neuritis in AIPs (100%, 20/20) was also higher compared with that of nAIPs (75.4%, 46/61; P = 0.017). Storiformed-fibrosis was more common in AIPs (95.0%, 19/20) than in nAIPs (1.6%, 1/61;P = 0.000). Pancreatic intraepithelial neoplasia (PanIN) was observed in 50.0%(10/20) of AIPs and 32.8%(20/61) of nAIPs, with a greater severity observed in AIPs (P = 0.031). Tubular complex (TC) was more commonly observed in AIPs (65.0%, 13/20) than nAIPs (26.2%, 16/61;P = 0.002). Among 81 cases of FMCP, 61 cases had less than 11 IgG4(+) plasmacytes /HPF, 7 cases had 10-30/HPF and 13 cases had over 30/HPF.</p><p><b>CONCLUSIONS</b>FMCPs include both AIP and nAIP. AIP has distinct pathological features and the presence of IgG4(+) plasmacyte is an important diagnostic parameter. FMCP appears to be an important precancerous lesion of pancreatic ductal adenocarcinoma. Surgery may be considered for patients with FMCP due to its mass-forming nature. In contrast, patients with AIP are treated medically due to its steroid-responsiveness. Therefore, accurate and timely diagnosis of AIP is of clinical relevance to avoid unnecessary surgical complications and to prevent progression of the disease.</p>

Expression and significance of neurogenic differentiation protein in pancreatic carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression and significance of neurogenic differentiation protein (NeuroD) in pancreatic carcinoma.</p><p><b>METHODS</b>The expression of NeuroD, PCNA and p53 proteins in 127 specimens of pancreatic carcinoma was detected by tissue microarray and immunohistochemestry. The correlations were analyzed between NeuroD and PCNA, p53, neural invasion, sleeve-like lymphocytic infiltration around the nerve, pancreatitis adjacent to carcinoma, lymph node metastasis and age, gender, location of tumors, histological types and differentiation of pancreatic carcinomas.</p><p><b>RESULTS</b>The positive rates of NeuroD, PCNA and p53 expression were higher in pancreatic carcinoma than those in non-tumor pancreatic tissues [64.6% (82/127) vs 10.5% (8/76), 57.5% (73/127) vs 9.2% (7/76), 59.1% (75/127) vs 9.2% (7/76), P < 0.01]. NeuroD expression in pancreatic carcinoma was related to that of PCNA and p53 and neural invasion (P < 0.05). No significant correlation was found between NeuroD and age, gender, tumor location, histological types and differentiation, sleeve-like lymphocytic infiltration, pancreatitis adjacent to the carcinoma and lymph node metastasis in pancreatic carcinomas.</p><p><b>CONCLUSIONS</b>NeuroD overexpression in pancreatic carcinoma. The overexpression of NeuroD may contribute to the tumorogenesis and development of pancreatic carcinoma, and is closely correlated to the cancer cell proliferation, p53 signal pathway and neural invasion in pancreatic carcinoma.</p>

Detection of human telomerase RNA component gene by fluorescent in situ hybridization for screening of cervical lesions / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the value of fluorescence in situ hybridization (FISH) detection of human telomerase RNA component (hTERC) gene amplification in screening of cervical lesions.</p><p><b>METHODS</b>A total of 146 post-thinPrep cytology test (TCT) samples were analyzed using FISH by two-color interphase probe targeting hTERC gene at chromosome 3q26 and the data were compared with the cytological and histological results.</p><p><b>RESULTS</b>FISH analysis was successful in 120 cases (20 cases of normal and 100 abnormal cases by TCT). Gene amplification of hTERC by FISH had a positive correlation with the cytological (r = 0.465, P < 0.01) and histological grade results (r = 0.610, P < 0.01). Extra copies of hTERC were seen in 28.6% (6/21) of CINI, 61.1% (11/18) of CINII, 75.0% (18/24) of CINIII and 91.7%(22/24) of squamous cell carcinoma, respectively. None (0/13) of the inflammation cases showed hTERC amplification. The sensitivity and specificity for detecting high grade lesions by FISH were 77.3% (51/66) and 82.4% (28/34); and the positive and negative predictive values were 89.5% and 65.1%, respectively. The rate of hTERC gene gain in high grade lesions was significantly higher than that in the low grade lesions (χ(2) = 32.550, P < 0.01). Combined with the high copy numbers, the sensitivity for detecting high grade lesions was increased to 81.2%.</p><p><b>CONCLUSIONS</b>Detection of hTERC gene amplification by FISH improves the screening efficiency of high-risk cervical epithelial lesions. The presence of high copy numbers of hTERC correlates with the presence of high grade cervical dysplasia.</p>

Fluctuations in the rate of autopsy in China / 中华医学杂志(英文版)

Autopsy has played a unique role in the progression of clinical medicine, medical education, epidemiology, and public health. However, the autopsy rate has been decreasing during the past several decades worldwide, and its necessity is frequently argued. Autopsy-based research in China, a country with the world's largest population, is very important for studying the spectrum and epidemiology of diseases as well as for discovering new diseases. This article summarizes the brief history of autopsy in China and analyzes the cause of its decline in recent decades by reviewing previously published papers, review articles, self-collected materials, and private correspondence. Since the first officially permitted autopsy in 1913, China witnessed the highest autopsy rate between 1950 and 1970, and since then the autopsy rate began to decline as it in other parts of the world. The main reasons for the reduction in autopsy rates in China include negligence by hospital administrators and relevant government authorities, unmotivated clinicians, helpless pathologists, unenforceable regulations and laws, and local cultures and customs.

Endoscopic retrograde cholangiopancreatography-guided brush cytology diagnosis of pancreatobiliary tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the cytologic features of pancreatobiliary tumors in endoscopic retrograde cholangiopancreatography (ERCP)-guided brushing preparations and to evaluate the usefulness of cytology in the diagnosis of pancreatobiliary malignancy.</p><p><b>METHODS</b>A retrospective analysis of 212 cases of ERCP-guided brush cytology smears performed during the period from January, 2004 to December, 2006. The cytologic diagnosis was confirmed either by the histologic diagnosis or the strict clinical criteria.</p><p><b>RESULTS</b>Two of the cases studied were unsatisfactory for diagnosis, with no epithelial cells identified. One hundred and thirty-seven smears were diagnosed as "negative", 45 of which subsequently confirmed to be malignant (negative predictive value = 60.2%). Six of the 11 cases with "low-grade atypia" were proven to be malignant (positive predictive value = 54.5%), as compared to 19 of 23 cases of "high-grade atypia" (positive predictive value = 86.4%). All of the 41 cases with cytologic diagnosis of "malignancy" were confirmed to be malignant (positive predictive value = 100%). The cytologic features of malignancy in ERCP-guided brushing preparations included overlapping nuclei, anisonucleosis, coarse chromatin pattern, poor cellular cohesion, tumor diathesis, prominent nucleoli and atypical mitotic figures.</p><p><b>CONCLUSIONS</b>The accuracy of ERCP-guided brush cytology relies on good specimen preparation and application of morphologic criteria. Grading of cytologic atypia is of clinical significance. A "negative" or "low-grade atypia" cytologic diagnosis requires further diagnostic workup to rule out the possibility of underlying malignancy, while a "high-grade atypia" or "malignant" diagnosis is relatively specific in guiding subsequent management of suspected pancreatobiliary malignancy.</p>

Solitary plasmacytoma of spine: a clinical, radiologic and pathologic study of 13 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinical, radiologic and pathologic features of solitary plasmacytoma of spine.</p><p><b>METHODS</b>The clinical, radiologic and pathologic features, as well as treatment and follow-up data, of 13 solitary plasmacytoma of spine cases were retrieved and analyzed. Immunohistochemical study using EnVision method for LCA, CD19, CD20, CD79a, CD3, CD7, PC, MUM1, CD138, IgG, IgM, kappa, lambda and Ki-67 was carried out.</p><p><b>RESULTS</b>All the tumours were primarily located in the vertebrae (including 9 cases in thoracic vertebrae and 4 cases in lumbar vertebrae). The male-to-female ratio was 3.3:1. The age of the patients ranged from 42 to 69 years (mean age = 56 years). The commonest symptom was pain in the surrounding regions. The degree of neurologic disturbance mostly depended on the extent of vertebral destruction and structural instability of the spine. Radiologic examination showed mainly osteolytic lesions in vertebrae. Magnetic resonance imaging demonstrated the presence of heterogeneous intensity inside the involved vertebrae (low in T1 weighted and high in T2 weighted images). Histologic examination showed diffuse infiltration by malignant cells. In well-differentiated plasmacytomas, the tumor cells resembled normal plasma cells. In poorly differentiated examples, the cellular morphology mimicked that of the centroblasts. The interstitial stroma was scanty and contained plenty of vessels, sometimes with formation of blood lakes. Amyloid deposition was present in some of the cases. Immunohistochemical study showed that the tumor cells were positive for CD79a and negative for CD20. Light chain restriction was detected in all the 13 cases studied. Plasma cell marker PC was expressed in all cases, while IgG was positive in 5 cases, IgM in 1 case, MUM1 in 10 cases and CD138 in 8 cases. Ki-67 index varied from 10% to 50%. All cases were operated, with adjuvant chemotherapy and radiotherapy given.</p><p><b>CONCLUSIONS</b>Correlation of clinical, radiologic and pathologic features is important in diagnosis of solitary plasmacytoma of spine. The possibility of multiple myeloma needs to be excluded. Early detection by radiologic examination, local surgical resection, post-operative chemoradiotherapy and long-term follow-up are prudent for successful management of this condition.</p>

Hepatitis B virus X protein inhibits hepatoma cell growth in vitro through p14(ARF)-dependent and p14(ARF)-independent pathways / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effects of hepatitis B virus X protein (HBx) on hepatoma cell growth through p14(ARF)-dependent and p14(ARF)-independent pathways.</p><p><b>METHODS</b>HBx and p14(ARF) were transfected either separately or in combination into HepG2 cells containing wt-p53 but not expressing p14(ARF). The cells were divided into 4 groups, namely pcDNA3 (control), pcDNA3HBx, pcDNA3p14(ARF), and pcDNA3HBx + pcDNA3p14(ARF) groups. Flow cytometry was used to examine the apoptosis rates and cell cycle progression of HepG2 cells in different groups. The expression of p14(ARF), MDM2, p53, and p21(WAF1) proteins were investigated by detecting the activity of p21(WAF1) promoter-luciferase and using Western blotting.</p><p><b>RESULTS</b>The apoptosis rates of HepG2 cells in pcDNA3HBx and pcDNA3p14(ARF) groups were significantly higher than that in the control group (14.11%, 13.72% vs 10.66%). Compared with the control group, pcDNA3HBx and pcDNA3p14(ARF) groups also showed significantly higher cell percentages arrested at G(0)/G(1) phase (63.62%, 61.75% vs 57.42%), luciferase activity of p21 promoter (1.25-/+0.05, 1.09-/+0.06 vs 0.77-/+0.03) and expressions of p53 and p21(WAF1). The cell apoptosis rate, percentage of cells in G(0)/G(1) phase and expression level of p14(ARF) were even higher in pcDNA3HBx+pcDNA3p14(ARF) group (18.61%, 66.74%, and 3.53-/+0.43, respectively) than in either p14(ARF) or HBx group.</p><p><b>CONCLUSION</b>HBx induces p53 expression through p14(ARF)-dependent and independent pathways to activate p21(WAF1) promoter, leading to G(0)/G(1) arrest and apoptosis of HepG2 cells.</p>

Effect of siRNA targeting centromere protein-A gene on biological behavior of HepG2 cells / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the influence of siRNA inhibition of CENP-A expression on the biological behavior of HepG2 cells.</p><p><b>METHODS</b>Three pairs of 21 bp reverse repeated motifs of CENP-A target sequence with 9 spacer were synthesized and inserted into vector pSilencer 2.1-U6 neo to generate siRNA eukaryotic expression plasmids. After stable transfection into HepG2 cells, cell growth, apoptosis, cell cycles and plate clone forming efficiency were investigated. Expressions of CENP-A mRNA was monitored by the reverse transcriptase polymerase chain reaction (RT-PCR). The protein expression of CENP-A, bcl-2, Bax, p53, p21waf1 and mdm2 were detected by Western-blotting.</p><p><b>RESULTS</b>Two eukaryotic expression plasmids with significant siRNA specific inhibition to the CENP-A gene were created. Compared with control cells, HepG2 cells transfected with the constructs showed G1 phase delay (P < 0.01) and cell number decrease in the S phase (P < 0.001), along with an increased apoptotic rate (P = 0.003), significant increase of Bax expression and decreased bcl-2 expression (P< or =0.001). The protein expressions of p21waf1 was higher and mdm2 was lower than those of the control groups. However, the wild type p53 protein expression was not effected by CENP-A siRNA.</p><p><b>CONCLUSIONS</b>An altered expression of CENP-A may be related to the proliferation of hepatocellular carcinoma through cell cycle regulation involving an altered bcl-2/Bax expression, that may be p53 independent.</p>

Unusual expression and molecular mechanisms of E-cadherin, beta-catenin in correlation with clinicopathologic parameters in neuroblastoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of E-cadherin and beta-catenin in neuroblastomas of various degrees of differentiation, and to investigate their molecular mechanisms in correlation with clinicopathologic parameters.</p><p><b>METHODS</b>Immunohistochemistry EnVision method was used to detect E-cadherin and beta-catenin expression in 90 paraffin-embedded tissue samples of neuroblastomas. The methylation status of CpG islands of E-cadherin promoter was investigated by MSP in 7 fresh tissue and 24 paraffin-embedded tissue samples. The mutation status of exon 3 of beta-catenin gene was studied by PCR in 7 fresh tissue samples. Statistical analysis of the data was performed by SPSS software.</p><p><b>RESULTS</b>E-cadherin and beta-catenin were abnormally expressed in neuroblastomas in general. The expression of beta-catenin in well-differentiated neuroblastoms was markedly higher (47/70, 67.1%) than that of the poorly differentiated tumors (8/20, 40.0%). There was a markedly decreased expression of both genes in tumors with lymph node metastasis than those without. Demethylation was seen in some regions of the promoter of E-cadherin in 31 cases of nuroblatomas. PCR of the exon 3 of beta-catenin followed by DNA sequencing demonstrated rearrangements and mutations in 7 cases, including 2 cases harboring identical point mutation at gene position 27184, leading to a T-->A alteration.</p><p><b>CONCLUSIONS</b>The abnormal over-expression of E-cadherin in neuroblastomas is independent of the methylation status of their promoter sequences. The abnormal expression of beta-catenin may be related to mutational changes at exon 3 of the gene.</p>

Expression of centromere protein A in hepatocellular carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of centromere protein A (CENP-A) and its significance in hepatocellular carcinoma (HCC) and adjacent non-neoplastic liver tissue.</p><p><b>METHODS</b>The expression levels of CENP-A mRNA in 20 samples of HCC and adjacent non-neoplastic liver tissue were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and real-time quantitative polymerase chain reaction (qRT-PCR). Immunohistochemical study for CENP-A and p53 proteins was also performed on tissue microarrays containing 80 samples of HCC and adjacent liver tissue.</p><p><b>RESULTS</b>The expression level of CENP-A mRNA in HCC (0.64 +/- 0.18) was higher than that in adjacent non-neoplastic liver tissue (0.09 +/- 0.09) (t = 12.78, P < 0.01). Of the 80 samples of HCC, 57 cases (71.25%) and 60 cases (75%) expressed CENP-A and p53 proteins respectively. The positivity rates of CENP-A and p53 proteins in non-neoplastic liver tissue were 43.75% (35/80) and 16.25% (13/80) respectively. There was a statistically significant difference in CENP-A and p53 protein expression between HCC and non-neoplastic liver tissue (P < 0.01). The coincident rate between CENP-A and p53 expression was 88.75% (71/80). Expression of CENP-A protein showed a positive correlation with that of p53 protein (r = 0.57, P < 0.01).</p><p><b>CONCLUSION</b>The over-expression of CENP-A occurs at transcriptional level and may be related to malignant proliferation of HCC via possible interaction with p53 gene.</p>

Expressions of nm23, P53 and S100A4 proteins and their relationships with metastasis potential in gastric carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression levels of nm23, P53, and S100A4 in gastric carcinoma and their relationships with clinicopathologic parameters and metastasis potential.</p><p><b>METHODS</b>Pathological specimens from gastric carcinoma,matched para-tumor tissues, metastatic lymph node and distant metastatic tissues were examined for the expression levels of nm23, P53, and S100A4 proteins by tissue microarray technique and immunohistochemistry.</p><p><b>RESULTS</b>The expression levels of P53 and S100A4 were upregulated (P< 0.01), while the expression of nm23 downregulated (P< 0.05) in gastric carcinoma compared with non-tumor tissues. S100A4 expression was significantly higher in distant metastatic tissues, while nm23 lower in metastatic lymph nodes than those in cancer tissues. Upregulating expression levels of nm23, P53, and S100A4 were significantly correlated with some malignant behaviour of gastric cancer. The expression rates of nm23+/P53+, P53+/S100A4+, and nm23+/S100A4+ immunohistochemical phenotypes were 48/74 (64.9%), 50/74 (67.6%), and 39/74 (52.7%). P53+/S100A4+, nm23+/S100A4+, and nm23+/P53+/S100A4+ phenotypes were associated with high metastasis potential of gastric cancer.</p><p><b>CONCLUSIONS</b>Alteration of nm23, P53, and S100A4 expression may contribute to the development of gastric carcinoma. Nm23 and S100A4 proteins play a critical role in tumor metastasis. Co-detection of the expression of P53, nm23, and/or S100A4 can be used to evaluate high metastasis potential of gastric cancer.</p>

Mucinous noncystic (colloid) adenocarcinoma of the pancreas / 中华病理学杂志

<p><b>OBJECTIVE</b>To determine the clinicopathologic characteristics and the relationship between related gene expression and pathobiologic behavior of pancreatic mucinous noncystic adenocarcinoma.</p><p><b>METHODS</b>Among the 249 pancreatic carcinoma cases from the department files, 6 tumors were identified to meet the pathologic criteria of colloid carcinoma. Envision immunohistochemical staining technique was used to detect expression of p21(ras), p21(WAF1), p16, p33(ING1), p53, ATM, MDM2, PCNA, Cyclins (D1, D3, A, B and E). Intra- and extra- cellular mucin production were determined by AB-PAS staining. Clinically, all of 6 cases were followed to June, 2003.</p><p><b>RESULTS</b>In all 6 cases, the tumors were located in the head of the pancreas and all displayed similar microscopic findings. Duodenal invasion was seen in 4 cases and perineural invasion was seen in 1 case. Tumor metastasis in the liver was seen in 2 cases and in the regional lymph nodes in 2 cases. Positive immunostaining was seen in 5 cases with p21(ras), 3 cases with p21(WAF1), 1 case with p16, 4 cases with p33(ING1), 2 cases with p53, 3 cases with ATM, 3 cases with MDM2, 6 cases with PCNA, 3 cases with cyclinA, 3 cases with cyclinD1, 4 cases with cyclinD3, 4 cases with cyclinB and 6 cases with cyclinE. Both extracellular and intracellular mucin was strongly positive for AB-PAS staining. Clinical follow-up found that 2 patients died of their tumors at 14 and 20 months. Three patients were alive after 28, 49 and 87 months of follow-up. One case were lost contact.</p><p><b>CONCLUSIONS</b>Pancreatic mucinous noncystic adenocarcinoma has distinct morphologic features and biologic behavior. Multiple gene products including many cyclins may be involved in the pathogenesis of pancreatic colloid carcinoma. The tumor has an aggressive behavior with a high frequency of invasion and metastases, though the prognosis could be better than that of ordinary ductal adenocarcinoma of pancreas.</p>

Influence of Smad4-independent pathway of transforming growth factor beta1 on the biological activity of pancreatic cancer cells / 中华病理学杂志

<p><b>OBJECTIVE</b>To study effects of the expression of transforming growth factor (TGF)-beta1 on the growth of Smad4-null pancreatic cancer cells.</p><p><b>METHODS</b>TGF-beta1 eukaryotic expression vector was transfected into pancreatic cancer cell line BxPC3. Effects of the expressison of TGF-beta1 was studied by growth curve analysis and flow cytometry. Cell motility was monitored by wound-healing assay. Western blot was used to estimate the expression level of p21(WAF/CLIP1), a cyclin-dependent kinase inhibitor.</p><p><b>RESULTS</b>Transfection of TGF-beta1 changed the morphology of BxPC3 into spindle shaped cells. The growth rate of BxPC3 began to decrease after the fourth day of TGF-beta1 transfection, compared with the control groups. Flow cytometry showed that the percentages of cells in the S phase were (27.53 +/- 0.02)%, (26.32 +/- 0.01)% and (17.01 +/- 0.03)% in naïve BxPC3, vector-control group and TGF-beta1 transfection group respectively. Lesser cells entered the S phase after TGF-beta1 transfection (P < 0.01), but no difference was seen between the BxPC3 and vector groups (P > 0.05). The expression of p21(WAF/CLIP1) increased upon the expression of TGF-beta1.</p><p><b>CONCLUSION</b>The Smad4-independent pathway of TGF-beta1 not only induces epithelial-mesenchymal transition in pancreatic cancer BxPC3, but also inhibits its growth through the up-regulation of p21(WAF/CLIP1).</p>

Hepatitis B virus and deletion of its COOH-terminal forty amino acids: proliferative impact on hepatoma cell line SMMC-7721 / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the biological impact of 40 amino acid deletion at the C-terminal of hepatitis B virus X on the proliferation of hepatoma cells.</p><p><b>METHODS</b>Cells of SMMC-7721 hepatoma cell line were transfected with HBx and its derivative HBx3'-40, harboring the 40 amino acid deletion at the distal C-terminal region. Cell growth curve, colony formation in soft agar plate and tumorigenesis assay in nude mice were used to observe the alterations induced by the transfection of HBx and HBx3'-40. The expression level of PCNA in tumor cells was also investigated.</p><p><b>RESULTS</b>The growth rates of the cells transfected with HBx and HBx3'-40 were markedly increased as compared with that of the control group. The colony formation rates were enhanced in the cells transfected with HBx(48.7 +/- 8.1) and HBx3'-40 (82.8+/-6.0), comparing with the control (26.9 +/- 3.5) %. In the tumorigenic assay, the size and weight of tumors were significantly increased in the cells transfected with HBx (0.412 +/- 0.212, 0.395 +/- 0.159) % and HBx3'-40 (1.476 +/- 0.232, 0.987 +/- 0.279) %, as compared with the control group (0.051 +/- 0.024, 0.033 +/-0.004) %. The expression level of PCNA in tumors was increased in both HBx (59.00 +/- 2.58) % and HBx3'-40 (69.25 +/- 3.77) % transfected cells, comparing with the control (37.67 +/- 2.52) %. Overall, the cells transfected with HBx3'-40 demonstrated the highest proliferative capacity.</p><p><b>CONCLUSION</b>The deletion of 40 amino acids in the C-terminal of HBx is correlated with an enhanced proliferation of hepatoma cells and may play an important role in the malignant transformation of the liver.</p>

Expression of proteins in p53 (p14ARF-mdm2-p53-p21WAF/CIP1) pathway and their significance in exocrine pancreatic carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of p14(ARF), p53, mdm2 and p21(WAF/CIP1) proteins and their relationship in exocrine pancreatic carcinoma.</p><p><b>METHODS</b>Specimens of pancreatic carcinoma, adjacent non-neoplastic pancreatic tissue and pancreatic benign lesions were examined for p14(ARF), p53, mdm2 and p21(WAF/CIP1) protein expression by tissue microarray technique and immunohistochemistry.</p><p><b>RESULTS</b>The expression of p14(ARF), p53, mdm2 and p21(WAF/CIP1) proteins in pancreatic carcinoma were 35.3% (59/167), 57.5% (96/101), 64.1% (107/167) and 39.5% (66/167) respectively. The expression of p53 proteins was increased in pancreatic carcinoma (P < 0.01), while the expression of p14(ARF) and p21(WAF/CIP1) proteins was reduced (P < 0.05), as compared with that in non-neoplastic pancreatic tissue. p21(WAF/CIP1) protein expression in pancreatic carcinoma significantly correlated with the age of patients and perineural invasion (P < 0.05). p53 protein expression correlated significantly with tumor differentiation, lymph node metastasis and perineural invasion (P < 0.05). Mdm2 protein expression correlated significantly with tumor differentiation (P < 0.05), while p14(ARF) protein expression correlated significantly with the age of patients and metastasis (P < 0.05). There was also statistic correlation between the expression of these four genes (P < 0.05).</p><p><b>CONCLUSIONS</b>Overexpression of p53 and mdm2 and loss of p14(ARF) and p21(WAF/CIP1) expression may contribute to the pathogenesis of pancreatic carcinoma. These proteins play a critical role in cell cycle arrest and apoptosis after DNA damage through p14(ARF)-mdm2-p53-p21(WAF/CIP1) pathway. Detection of p53 and Mdm2 protein overexpression may be useful in evaluation of the aggressiveness of pancreatic carcinoma.</p>

Fine needle aspiration cytology of eyelid sebaceous gland carcinoma and its differential diagnosis / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the fine needle aspiration cytology (FNAC) features and differential diagnosis of eyelid sebaceous gland carcinoma.</p><p><b>METHODS</b>Four cases of eyelid sebaceous gland carcinoma diagnosed by FNAC were reported and confirmed by biopsy. Three of the cases were in early stages with tumor sizes smaller than 10 mm in diameter and without metastasis. The smears were stained by routine H & E and SudanIII methods. The cytologic findings were described and compared to corresponding histological features, and moreover, compared to chalazion, pilomatrixoma and eyelid basal cell carcinoma.</p><p><b>RESULTS</b>Neither hemorrhage nor infection were found after the examination. Abundant cells were observed in the sebaceous carcinoma FNAC smears. Two types of tumor cells were found: one showed tumor cells differentiating toward sebaceous gland, with large pale cells and vacuolated cytoplasm, the other demonstrated poorly-differentiated cell with dark and irregular nuclei. Numerous vacuoles with inequality of size were found in cytoplasm or in background in all four cases, and the SudanIII stain showed that these vacuoles contained lipid. Some smears demonstrated cells with basaloid, fusiform or squamous features, corresponding to various histopathological types. In contrast, smears of chalazion displayed inflammatory granuloma, containing several types of inflammatory cells without malignant cells. Smears of pilomatrixoma were cellular with three cell populations, which included bland sheets of basaloid cells, nucleated basophilic cells and anucleated keratinized "ghost cells", along with calcific debris. The smears of basal cell carcinoma were typically less cellular, more tightly cohesive and had smaller clusters of uniform hyperchromatic basaloid cells without vacuolization in cytoplasm or background. Overall, the cytological features of eyelid sebaceous carcinoma were distinct from those of chalazion, pilomatricoma and basal cell carcinoma.</p><p><b>CONCLUSIONS</b>FNAC is a safe and effective approach for the diagnosis of eyelid sebaceous carcinoma and lipid stain is useful in differential diagnosis. The application of FNAC may be important in reaching an early diagnosis and initial treatment of eyelid nodule.</p>

Interaction effect of p53 with HBV in hepatoma cell line SMMC-7721 / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To study the interaction of hepatitis virus B (HBV) and tumor suppressor p53.</p><p><b>METHODS</b>Plasmid pCMVp53 was transfected or cotransfected with pCMVHBVa (wild type HBV) or PCMVHBVb (mutant type HBV) into the hepatoma cell line SMMC-7721 by lipofectamine. Apoptosis cells were labeled by annexin V-FITC and confirmed by flow cytometry. Reporter plasmids PG13-CAT or p21-luc were cotransfected respectively in each group to indicate transactivation activity of p53 and it's effect on p21 promoter. Western blot was performed to observe p53 expression in each group.</p><p><b>RESULTS</b>The group transfected by pCMVp53 alone exhibit higher luciferase activity and higher apoptosis rate, otherwise, p53 expression, enzyme activity of PG13-CAT or p21- luc and cell apoptosis rate were much higher in the group cotransfected by pCMVp53 and pCMVHBVa, but not in the other cotransfected group; HBV replication was enhanced in p53 cotransfected group.</p><p><b>CONCLUSION</b>p53 expression and effects could be enhanced by HBV and p53 had positive regulation effect on HBV replication.</p>

Immunohistochemical demonstration of cyclins A, B, D1, D3 and E in hepatocellular carcinomas using tissue microarrays / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of five kinds of cyclins in hepatocellular carcinoma (HCC) and their association with degree of tumor differentiation, metastasis and infection of hepatitis B virus (HBV).</p><p><b>METHODS</b>The HCC tissue microarrays were composed of those from 273 cases of HCC tissues, 144 surrounding-tumor liver tissues and 10 normal liver tissues obtained from autopsy. The diameter of each specimens on tissue microarrays was 2.0 mm. Immunohistochemistry was used to detect the expression of cyclin A, cyclin B, cyclin D1, cyclin D3 and cyclin E on HCC tissue microarrays. The association of the expression of these cyclins with the infection rate of HBV was also analyzed.</p><p><b>RESULTS</b>Three paraffin-embedded HCC tissue microarrays were successfully constructed, including 136, 143 and 148 tissue spots, respectively. The positive rates of cyclins in 273 cases of HCC were cyclin A 52.7%, cyclin B 45.4%, cyclin D1 35.9%, cyclin D3 44.3% and cyclin E 23.1%; while the figures in 144 surrounding-tumor tissues were 8.3%, 5.6%, 4.9%, 6.3% and 1.4%, respectively. In 10 normal liver tissues these cyclins exhibited negative staining, with the exception that cyclin D1 was positive in one case of normal liver tissue. The positive rate of cyclins in HCC were significant higher than those in surrounding-tumor liver tissues (P < 0.01), in HCC tissues with histological grade II and III, the cyclins expression were stronger than that in grade I (P < 0.05). The positive rates of cyclins, except cyclin A in HCC with portal vein invasion were higher than those without portal vein invasion (P < 0.01). Infection of HBV did not have significant relationship with the expression of cyclins (P > 0.05).</p><p><b>CONCLUSION</b>Cyclins in different cell cycles overexpressed at varied levels in hepatocellular carcinoma, and the increased expression of cyclins may shorten the tumor cell cycle phase, accelerate cell proliferation, and have a close relationship with HCC aggressiveness.</p>

The role of hepatitis B virus X gene and p53 on hepatocellular carcinoma cell growth / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the effects of hepatitis B virus X gene and p53 on hepatocellular growth.</p><p><b>METHODS</b>Two kinds of plasmids containing sense and antisense human wild p53 gene respectively were constructed. SMMU-7721 cells were transfected with HBx, sense-wtp53 antisense-wtp53 separately or cotransfected with either HBx and sense-wtp53 or HBx and antisense-wtp53. Flow cytometry was adopted to measure the apoptosis rates and the effects of HBx on cell cycle progression. The activity of p21(Waf1) promoter-luciferase construct was detected. Growth curves for SMMU-7721 stably transfected with pcDNA3 and pcDNA3HBx were analyzed.</p><p><b>RESULTS</b>After doxorubicin administration, HBx was noticed able to initiate apoptosis of the liver cells. The apoptosis rate was 5.32% in the pcDNA3 transfected and 12.66% in the pcDNA3HBx transfected groups respectively. HBx could also abrogate p53-mediated apoptosis. The apoptosis rate in groups transfected with pcDNA3, pcDNA3wtp53 and pcDNA3HBx + pcDNA3wtp53 was 5.32%, 11.72% and 4.67% respectively. In compared with the normal group, the number of cells in transiently HBx-expressed group and HBx-transfected group decreased 4.79% and 10.25% respectively. HBx inhibited the activity of p21(Waf1) promoter-luciferase constructed (P < 0.05) and promoted cell growth. The growth rate of HBx expression cells was faster.</p><p><b>CONCLUSION</b>Under DNA damage, HBx reduced expression of p21(Waf1) by repressing the activity of p53 protein, followed by disturbing the regulation of G(0)-G(1) cell cycle checkpoint, and promoted the growth rate of hepatoma cells.</p>

An experimental study of immune function effect of rats irradiated with the complex field cure instrument / 中国医疗器械杂志

The complex field cure instrument is a new medical instrument with which an experiment was carried out. Rats were continuously irradiated by the complex field for 90 days, with a day's total dose of 285.9 M.T.G. while other rats weren't irradiated for control group. The animals were respectively killed at 7d, 14d, 30d, 60d and 90d, and their blood samples were taken for cell and humoral immune analysis. The results show that values of lymphocyte transform rate, soluble receptor (SIL-2R), total hemolytic complement levels (CH50) and immunoglobulin (A.G.) after irradiation are more than those of the control group having proved that the instrument may improve immune function of rats.