To emphasize the importance of specimen fixation and improve quality of diagnosis of gastrointestinal stromal tumor / 中华胃肠外科杂志

The most common problem in the diagnosis of gastrointestinal stromal tumor (GIST) is inadequate specimen fixation. The paper focused on specimen fixation and standardized protocol in immunohistochemistry staining and gene mutation detection. We have adjusted some procedure used in immunohistochemistry staining and c-kit gene detection to improve the quality of inadequately fixed specimen. It maybe useful for clinicians, pathologists and technicians working in immunohistochemistry labs and gene detection labs.

Clinicopathologic study of 963 cases of mature T-cell and natural killer/T-cell lymphoma with respect to 2008 WHO classification of lymphoid neoplasms / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of various types of mature T-cell and natural killer (NK)/T-cell lymphoma in Guangdong, China, with respect to the 2008 WHO classification of lymphoid neoplasms.</p><p><b>METHODS</b>Eleven hundred and thirty-seven (1137) cases of mature T-cell or NK/T-cell lymphoma diagnosed during the period from 2002 to 2006 in Guangzhou area were retrieved. The clinical data, histologic features and immunohistochemical findings were reviewed by a panel of experienced hematopathologists. Additional immunostaining was performed if indicated. The cases were re-classified according to the 2008 WHO classification of lymphoid neoplasms.</p><p><b>RESULTS</b>Nine hundred and sixty-three (963) cases fulfilled the diagnostic criteria of mature T-cell or NK/T-cell lymphoma and accounted for 20.1% of all cases of lymphoma encountered during the same period (963/4801). A predominance of extranodal involvement was noted in 644 cases (66.9%), while 319 cases (33.1%) showed mainly nodal disease. The prevalence of various lymphoma subtypes was as follows: peripheral T-cell lymphoma, unspecified (PTCL, NOS) 293 cases (30.4%), extranodal NK/T-cell lymphoma, nasal type 281 cases (29.2%), anaplastic large cell lymphoma (ALCL) 198 cases (20.6%), and angioimmunoblastic T-cell lymphoma (AILT) 46 cases (4.8%). The male-to-female ratio was 1.99. The median age of the patients was 44 years, with the peak age of PTCL, NOS, extranodal NK/T-cell lymphoma, nasal type and AILT being 55 to 64 years, 25 to 54 years and 65 to 74 years, respectively. ALK-positive ALCL occurred more frequently in young age, while the ALK-negative ALCL cases occurred mainly in the elderly.</p><p><b>CONCLUSIONS</b>Extranodal lesions predominate in mature T-cell and NK/T-cell lymphomas occurring in Guangzhou area. There is a male predominance and the overall incidence shows no increasing trend with age of the patient. The peak age of various subtypes however varies. The most common subtype was PTCL, NOS, followed by extranodal NK/T-cell lymphoma, nasal type, ALCL and AILT. The relatively frequent occurrence of extranodal NK/T-cell lymphoma, nasal type in Guangdong area is likely associated with the high incidence of Epstein-Barr virus infection there.</p>

Subgrouping and outcome prediction of diffuse large B-cell lymphoma by immunohistochemistry / 中华病理学杂志

<p><b>OBJECTIVE</b>To categorize diffuse large B-cell lymphoma (DLBCL) into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subgroups by immunohistochemistry; and to investigate the underlying prognostic significance.</p><p><b>METHODS</b>Immunohistochemical study for CD10, bcl-6 and MUM1 was performed on 133 cases of DLBCL. The cases were then categorized into GCB and non-GCB subgroups. The 5-year overall survival and 5-year progression-free survival rates were compared between the GCB and non-GCB groups, and among the cases with different immunohistochemical expression or with different IPI.</p><p><b>RESULTS</b>Amongst the 133 case studied, CD10 was expressed in 33.1%, while bcl-6 was positive in 34.6% and MUM1 in 45.1%. CD10 expression had a favorable impact on 5-year overall survival (P=0.041) and 5-year progression-free survival (P=0.031). On the other hand, bcl-6 expression had a favor able impact on 5-year progression-free survival (P=0.044). Expression of MUM1 carried an adverse effect on 5-year overall survival (P=0.031) and 5-year progression-free survival (P=0.028). GCB immunophenotype was demonstrated in 40.6% of the cases, while 59.4% showed a non-GCB profile. GCB DLBCL had a significantly longer 5-year overall survival (P=0.004) and 5-year progression-free survival (P=0.003), as compared with the non-GCB group. When dividing the cases into two groups according to their IPI score (IPI=0 to 1 and IPI=2 to 5), it turned out that the 5-year overall and progression-free survival rates of the GCB group were significantly higher than those of the non-GCB group (P=0.019 and 0.014 respectively in cases with IPI of 0 to 1 and P=0.006 and 0.009 respectively in cases with IPI of 2 to 5). The non-GCB cases with a IPI of 2 to 5 had the poorest prognosis.</p><p><b>CONCLUSION</b>DLBCL subgrouping by immunohistochemistry and analysis of the subgrouping with IPI is feasible and useful in predicting clinical outcome.</p>

Expression of syndecan-1 at different stages in the course of gastric carcinoma and its significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of syndecan-1 protein at different stages in the course of gastric carcinoma and its significance in carcinogenesis and metastasis.</p><p><b>METHODS</b>There were 56 cases of chronic gastritis, 50 cases of chronic atrophic gastritis, 59 cases of intestinal metaplasia, 61 cases of displasia, and 112 cases of gastric carcinoma. Among the carcinoma cases, 55 were without and 57 with lymph node metastases. All paraffin-embedded tissue samples were assessed by immunohistochemistry.</p><p><b>RESULTS</b>The syndecan-1 positive rate was 96.43% (54/56) in gastritis, 98.00% (49/50) in chronic atrophic gastritis, 100.00% (59/59) in intestinal metaplasia, 91.80% (56/61) in displasia, 45.45% (25/55) in gastric carcinoma without, and 24.56% (14/57) in gastric carcinoma with lymph node metastases. There was no significant difference among chronic gastritis, chronic atrophic gastritis and intestinal metaplasia (P > 0.05). There was a significant difference between displasia group and gastric carcinoma group (P <0.05), as well as between gastric carcinoma with and without lymph node metastases. There was a significant difference among well, moderately and poorly differentiated carcinoma groups.</p><p><b>CONCLUSION</b>A decreasing expression of syedecan-1 in the development of gastric carcinoma is related with gastric carcinogenesis, and it may further promote metastasis of gastric carcinoma.</p>

Expression of peroxisome proliferator-activated receptor gamma, E-cadherin and matrix metalloproteinases-2 in gastric carcinoma and lymph node metastases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Peroxisome proliferator activated receptor gamma (PPARgamma) is a ligand-activated transcription factor. Activation of PPARgamma has recently been demonstrated to inhibit various tumor cells growth, progression and metastasis. E-cadherin-mediated cell adhesion system is now considered to be an "invasion suppressor system" in cancer tissues. Matrix metalloproteinases-2 (MMP-2) is a prerequisite for metastasizing tumor cells. However their correlation is still unknown in gastric carcinoma. The aim of this study was to assess the expression of PPARgamma, E-cadherin, MMP-2 and their correlation in gastric carcinoma and metastases.</p><p><b>METHODS</b>Gastric carcinoma tissues and their corresponding lymph nodes with metastases and the adjacent non-tumor tissues were obtained from 54 patients with gastric cancer who underwent gastrectomy. Expression of PPARgamma, E-cadherin and MMP-2 was assessed by immunohistochemical staining.</p><p><b>RESULTS</b>The nuclear expression level of PPARgamma in neoplastic cells was significantly lower than that in the normal controls (P < 0.001), with the expression of PPARgamma being weaker in primary tumors compared with that in metastases. In all neoplastic cells, E-cadherin was expressed with abnormal patterns (cytoplasm pattern, cytoplasm and membrane pattern or absent), compared with normal cells where E-cadherin was expressed with a normal pattern (membrane pattern). Compared with the normal tissues, the expression level of E-cadherin decreased in primary tumors and further decreased in metastases (P < 0.001). Membrane staining of MMP-2 was detected in the foveolar epithelia of normal gastric mucosa, whereas predominant cytoplasm staining of MMP-2 was found in malignant tissues. The expression of MMP-2 was stronger in metastatic tissues than in primary tumors. In neoplastic foci the expression of PPARgamma was negatively correlated with MMP-2 expression (P < 0.05). However, there was no correlation between E-cadherin and PPARgamma or MMP-2 expression.</p><p><b>CONCLUSIONS</b>Down-regulation of PPARgamma and E-cadherin and up-regulation of MMP-2 in neoplastic foci might be helpful to gastric carcinogenesis and metastases. An inverse relationship between PPARgamma and MMP-2 in human gastric carcinoma suggests that PPARgamma might modulate MMP-2 expression and affect gastric cancer metastases.</p>

Differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and T-cell/histiocyte-rich B-cell lymphoma (TCRBCL).</p><p><b>METHODS</b>15 cases of NLPHL and 16 cases of TCRBCL were studied on both morphology and immunophenotype according to the WHO classification of lymphoid neoplasms. SP-immunohistochemical staining were performed on paraffin sections. In situ hybridization for EBER1/2 and gene rearrangement of immunoglobulin heavy chain (IgH) were carried out in 3 cases of NLPHL and 4 cases of TCRBCL, respectively.</p><p><b>RESULTS</b>Histologically, a few atypical large cells scattered in a background of small lymphocytes with or without histiocytes were a common finding in both NLPHL and TCRBCL. Of NLPHL, nodular pathern predominated in 11 cases, diffuse patterns without nodules in 3 cases and one case showed nodular and diffuse pattern intermixed with a increased number of large cells. 14 cases of TCRBCL showed diffuse pattern. One case with micronodular pattern involving the splenic white pulp. One case showed a combination of nodules of NLPHL, diffuse areas of TCRBCL and a sheet of large cells of diffuse large B-cell lymphoma (DLBCL) within the same lymph node biopsy specimen. Immunophenotypically, the large cells showed and CD20, CD79a, bcl-6 and EMA positive, and CD15, CD30, CD3, CD45RO and LMP-1 negative. In NLPHL, small B cells and CD57 positive cells were common, whereas in TCRBCL, TIA-1 positive cytotoxic cells and histiocytes dominated, small B cells were scarce or absent. EBER1/2 were negative and gene rearrangement of IgH was found in all tested 3 cases of NLPHL and 4 cases of TCRBCL, respectively.</p><p><b>CONCLUSION</b>There are some morphologic and immunophenotypic resemblance between NLPHL and TCRBCL. A combination of the morphological characteristics and the reactivity of the background cells for CD57 and TIA-1 seem to reliably discriminate between the entities and should therefore help to increase the interobserver reproducibility of diagnosis in the gray zone around Hodgkin lymphomas.</p>

Effect of shRNA-mediated survivin gene silencing on apoptosis and proliferation of leukemia cell line / 中华血液学杂志

<p><b>OBJECTIVE</b>To transfect a short hairpin RNA (shRNA) against survivin gene into human T lymphoblastic leukemia cell line Jurkat, and to explore the effects on apoptosis and proliferation of transfected cells.</p><p><b>METHODS</b>The survivin-shRNA expression vector were constructed and transfected into Jurkat cells. Expression of survivin mRNA and protein were assessed by RT-PCR and Western blot analysis respectively. Apoptosis index of transfected Jurkat cells was quantified by flow cytometry. The potential of cell proliferation was described by cell growth curves.</p><p><b>RESULTS</b>In survivin-shRNA transfected Jurkat cells, survivin mRNA levels were significantly reduced by 66.67% ( transient transfection) and 60.69% ( stable transfection) respectively, compared with that in control-shRNA treated group and PBS treated group (P < 0.05); and the levels of survivin protein were significantly reduced by 63.41% (transient transfection) and 60.18% (stable transfection), compared with that in the two control groups (P < 0.05). Apoptosis index was significantly increased during both transient and stable transfection, respectively [(22. 41 +/- 2.83)% and (20.73 +/- 2.56)% (P < 0.05)]. Survivin-shRNA also inhibited the proliferation of Jurkat cells.</p><p><b>CONCLUSIONS</b>Vector-based survivin-shRNA can effectively reduce the expression of survivin gene, induce apoptosis</p>

Effect of survivin antisense mRNA transfection on the growth and chemotherapy sensitivity of lymphoma cells / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the effect of transfecting survivin antisense mRNA on growth and chemotherapy sensitivity of lymphoma cells.</p><p><b>METHODS</b>Eukaryotic expression plasmid pcDNA3. 1-antisense (As) survivin was constructed and transfected into Jurkat T lymphoblastic lymphoma cell lines with high expression survivin mRNA by use of lipofectmine gene transfer technique. Expression of survivin mRNA and protein were detected by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemical and Western blot. The effect of transfecting survivin antisense mRNA on the growth of Jurkat cell lines was monitored by population doubling time (PDT) and Apoptotic indexes (AI). The morphologic features were observed in transfected cells by light and electric microscopes. MTT assay was used to analyze the response of transfected cells to CTX and MTX.</p><p><b>RESULTS</b>Compared with the control cells, the expression of survivin mRNA and protein were reduced after transfected pcDNA3. 1-Assurvivin 48 h, 5 w and 6 w, PDT (52 h) was prolonged. Apoptotic indexes were higher in transfected antisense survivin mRNA cells [20.2% (48 h)], 6.2% (5 w) and 6.8% (6 w) than control ones [2.1%, 1.3% (48 h)] and [1.3% (5 w) and 1.0% (6 w)]. The cells grow slowly and the dead cells increase and some swelling and apoptotic cells were observed in transfected pcDNA3. 1-Assurvivin groups by invert, light and electric microscopes. The Jurkat cell line of transfected pcDNA3. 1-Assurvivin had higher sensitivity to CTX and MTX. The rate of inhibition was higher in transfected group. There is a significant difference between the transfected group and untransfected one, P < 0.05.</p><p><b>CONCLUSIONS</b>The result indicated that survivin gene was very important for growth of Jurkat cells. To inhibit the expression of survivin will be significant in therapy of T lymphoblastic lymphoma. Survivin gene might be a target of therapy.</p>

T-cell/histiocyte-rich B-cell lymphoma: histology, immunophenotype and differential diagnosis / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the histology, immunophenotype and differential diagnosis of T-cell/histiocyte-rich B-cell lymphoma (TCRBCL).</p><p><b>METHODS</b>A review of 245 cases of so-called Hodgkin lymphoma diagnosed during the period from 1980 to 2000 in 3 hospitals in Guangzhou, 8 cases were reclassified as TCRBCL, according to the 2001 World Health Organization classification of lymphoid neoplasms. An additional 8 cases of TCRBCL were retrieved from consultation files, as well as routine biopsy cases encountered between 2000 and 2004. Immunohistochemical studies were performed on paraffin-embedded tissue by SP technique in order to study the immunophenotype of the large neoplastic cells (CD20, CD79a, CD3, CD45RO, CD15, CD30, CD10, bcl-6 and EMA) and background non-neoplastic cells (CD3, CD8, CD20, CD45RO, CD79a, CD57, CD68, CD21, CD35, cyclin D1, TIA-1). In-situ hybridization for EBER 1/2 and immunoglobulin heavy chain gene rearrangement study were also performed in 4 and 4 cases respectively.</p><p><b>RESULTS</b>Among the TCRBCL cases studied, there were 8 males and 8 females. The age of patients ranged from 10 to 68 years old (mean = 40.3 years old). All had lymphadenopathy and hepatosplenomegaly. On presentation, 3 cases belonged to stage II, 10 cases stage III and 3 cases stage IV. Histologically, scattered atypical large neoplastic cells were seen in a background of small lymphocytes and sometimes histiocytes. The large cells exhibited CD20+, CD79a+, EMA+, CD15- and CD30- phenotype. On the other hand, the background small lymphocytes were CD3 and CD45RO-positive. Most of these background T cells expressed CD8 and TIA-1, while they were mostly CD57-negative. The histiocytic cells were CD68-positive; and CD21 and CD35-positive follicular dendritic cell meshworks were absent. In-situ hybridization for EBER 1/2 showed negative nuclear signals. Immunoglobulin heavy chain gene rearrangement study revealed clonal pattern in all the 4 cases tested.</p><p><b>CONCLUSIONS</b>TCRBCL is a rare subtype of lymphoma, with distinctive histology and immunophenotype. The above features are helpful in delineating this entity from Hodgkin lymphoma, reactive lymphoid hyperplasia and lymphomatoid granulomatosis.</p>