ABSTRACT
ObjectiveTo investigate the effect of Smad7 antisense oligodeoxynucleotide (ASODN) on proliferation in human pancreatic cancer cell line SW1990,with a focus on the expression of matrix metalloproteinase-2(MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2).To explore the underlying mechanism of the role of Smad7 in the pathogenesis and development of pancreatic cancer.MethodsSmad7 ASODN was transfected into SW1990 cells through lipofectamine.Nosense oligodeoxynucleotide (NSODN),ASODN and lipofectamine was used as control. The transfection efficiency was assessed by fluorescence microscopy and flow cytometry.The expressions of Smad7,MMP-2 and TIMP-2 in transfected cells were detectedby RT-PCR and Western blot.Cell viability was assessed by dimethyl thiazoldiphenyltetrazoliumbromide (MTT) method. Results Smad7 was expressed in SW1990 cells.The transfection efficiency of SW1990 was 81.2％.The expressions of Smad7 mRNA were 0.34 ± 0.06,0.95 ±0.07,1.03 ± 0.11 in transfected group,ASODN and lipofectamine group; and the expressions of MMP-2 mRNAwere 0.54 ± 0.08,1.15 ± 0.13,1.27 ± 0.16 ; and the expressions of TIMP - 2 mRNA were 0.26 ±0.07,0.72 ± 0.13,0.78 ± 0.17,the mRNA expressions were significantly reduced in Smad7 ASODN transfected group,compared with other two groups (P ＜0.01 ).The expressions of Smad7 protein were 0.14 ± 0.03,0.29 ± 0.05,0.28 ± 0.07 in transfected group,ASODN and lipofectamine group; the expressions of MMP-2 protein were 0.17 ±0.02,0.29 ±0.05,0.31 ±0.04,and the expressions of TIMP-2 protein were 0.20 ± 0.03,0.41 ± 0.11,0.43 ± 0.09,the protein expressions were significantly reduced in Smad7 ASODN transfected group,compared with other two groups (P ＜0.01 ).The A490 values of proliferation were 0.83 ± 0.03,1.02 ±0.02,0.99 ±0.02 in transfected group,ASODN and lipofectamine group,the proliferation were significantly reduced in Smad7 ASODN transfected group,compared with other two groups (P ＜0.01 ).ConclusionsSmad7 ASODN could effectively inhibit the expressions of Smad7,therefore decrease the expressions of MMP-2,TIMP-2 and reduce the proliferation.
ABSTRACT
Objective To evaluate the clinical significance of positive peritoneal cytology in patients with endometrial cancer.Methods The records of 315 patients with endometrial cancer who were operated at Cancer Hospital, Fudan University between January 1996 and December 2008 were reviewed.Peritoneal cytology were performed and diagnosed in all patients.Factors related with peritoneal cytology were analyzed by correlation analysis.Log-rank test and Cox regression test was used for the analysis of prognosis,respectively.Results (1) Peritoneal cytology were positive in 30 (9.5%) patients.Positive peritoneal cytology was associated with pathological subtype ( P = 0.013 ), stage ( P = 0.000 ), myometrial invasion ( P =0.012), lymph-vascular space invasion ( P = 0.012 ), serosal involvement ( P = 0.004 ), cervical involvement ( P = 0.016), adnexal involvement ( P = 0.000), and omental involvement ( P = 0.000), with no association with grade ( P = 0.152 ) and lymph node metastasis ( P = 0.066 ).( 2 ) Three-year overall survival (OS) and progression-free survival(PFS) were 93.0% and 85.5% ,respectively.Positive peritoneal cytology, surgical stage, pathological subtype, myometrial invasion, grade, and lymph-vascular space invasion were significantly associated with worse prognosis by univariate analysis ( P ＜ 0.05 ), while only surgical-pathology stage and myometrial invasion were independent prognostic factors by multivariate analysis ( P ＜ 0.05 ).For 30 cases with positive peritoneal cytology, the patients with no high risk factors shown significantly prognoses better than those with any risk factors.The results shown that for patients with late stage (stage Ⅲ - Ⅳ ) endometrial cancer with positive peritoneal cytology was significantly associated with the worse OS and PFS by multivariate analysis ( P = 0.006).Conclusions Positive peritoneal cytology was associated with serosal involvement, cervical involvement, adnexal involvement, omental involvement, and late stage.Therefore, peritoneal cytology should be performed and reported separately as a part of full surgical staging procedure.
ABSTRACT
Objective The purpose of this study was to evaluate gene amplification by chromogenic in situ hybridization (CISH) and the protein expression of Her-2/neu gene in patients with uterine papillary serous carcinoma ( UPSC) and to determine its prognostic value.Methods Thirty-six patients with confirmed pathologic diagnosis of UPSC in Cancer Hospital of Fudan University from Jan.1996 to Jan.2006,were analysed retrospectively.CISH was performed to assess Her-2/neu gene amplification,and protein expression was evaluated by immunohistochemistry (IHC).The prognostic factors were analyzed by log-rank test or Cox proportional hazard model.Results Among 36 cases with UPSC,13 patients (36.1% ) showed moderate staining (++) to strong staining (+++) for Her-2/neu protein,while amplification of the Her-2/neu gene by CISH was observed in 4 of the 36 (11.1% ) cases.Her-2/neu protein over-expression was significantly associated with advanced surgical stage and worse prognosis by univariate analysis ( P = 0.030 and P = 0.002,respectively),while the multivariate analysis shown that only Her-2/neu protein over-expression and deep myometrial invasion were associated with a poor prognosis ( P < 0.05 ).In 13patients with Her-2/neu protein over-expression,the mean survival period with chemotherapy was shorter than those without chemotherapy (20 vs.42 months,P = 0.370 ).Conclusion Her-2/neu protein over-expression is significantly associated with advanced surgical stage UPSC and poor survival outcome,and might reduce the chemotherapy sensitivity.
ABSTRACT
Objective To evaluate prognostic factors and treatment of patients with advanced stage endometrial cancer. Methods One hundred and eighteen patients with advanced stage endometrial cancer were treated in our hospital between January 1996 and December 2006. The treatment and prognosis were retrospectively analyzed. The mean follow-up time was 26 months. Results During the follow-up, 33 cases (28.0%) died and 25 patients(21.2% ) had disease progression. The 3-year overall survival for patients with stage Ⅲ and stage Ⅳ was 78. 3% and 39. 4%, and for endometrioid and nonendometrioid endometrial carcinoma was 69. 3% and 42. 0%, respectively. Four patients with positive cytology only were followed closely after surgery and were free of disease up to the report time. Patients with late stages, deep myometrial invasion, nonendometrioid endometrial cancer, poor differentiation, without lymphadenectomy and without radiochemotherapy after surgery were associated with a worse prognosis by univariate analysis (P < 0. 05 ),while in a multivariate analysis only late stages and deep myometrial invasion were associated with a poor prognosis ( P < 0. 05 ). The patients who received lymphadenectomy and whose residual disease after the surgery was less than 1 cm had better prognoses than those otherwise(P <0. 05). The patients who received postoperative radiochemotherapy had better prognoses than those who did not ( P <0. 05 ). Conclusions Pathological stage and myometrial invasion are independent prognostic factors for late stage endometrial cancer. Satisfactory cytoreduction surgery and lymphadenectomy, followed by postoperative radiochemotherapy, except for stage Ⅲa patients with positive cytology only, are recommended in order to improve prognosis.
ABSTRACT
Objective To study the expression of BCL10 and associated chromosomal aberration in primary cutaneous marginal zone B-cell lymphoma (PCMZL). Methods Tissue specimens were collected from 17 patients with PCMZL. Immunohistochemistry was used to detect the expression of BCL10. Fluorescence in situ hybridization (FISH) was performed to examine the presence of API2-MALT1 fusion gene and chromosomal aberration in BCL10, MALT1 as well as IgH genes in these cases. Results Of these patients,94.1% (16/17) expressed BCL10 protein. The cytoplasmic expression of BCL10 was observed in 64.7% (11/17) of the patients, and nuclear expression in 29.4% (5/17). As shown by FISH test, neither API2-MALT1 fusion gene nor chromosomal aberration in BCL10, MALT1 or IgH genes was present in these patients. Conclusions Compared with MALT lymphomas originating from tissues other than skin, PCMZL is uncommonly associated with chromosomal abnormalities; it is possible that there are unknown factors contributing to its tumorigenesis. Nuclear BCL10 is unrelated to the presence of chromosomal aberration in BCL10, MALT1 or IgH genes. Further follow-up is required to clarify the association between nucle ar BCL10 and poor prognosis of PCMZL.
ABSTRACT
Background and purpose:Bone marrow cytomorphology is the main approach for determination of bone marrow involvement in patients with malignant lymphomas. In recent years, with the development of detection of cellular surface markers and molecular biology, flow cytometry (FCM) and polymerase chain reaction (PCR) were gradually applied in the detection of bone marrow in malignant lymphomas. Because such systematic research has not been done domestically , we performed a study to compare diagnostic value and clinipathological signifi cance of cytomorphology of bone marrow aspirates, immunophenotype detected by flow cytometry and immunoglobulin heavy chain gene rearrangement detected by polymerase chain reaction in bone marrow of B cell lymphomas. Methods: Bone marrow cytomorphology, FCM and PCR were simultaneously carried out in 75 bone marrows of B cell lymphoma and compared with each other. Results:(1)16 were demonstrated by cytomorphology, 36 by FCM, 33 by PCR. The positive rates were 21.3%, 48% and 44% respectively. The differences among these three methods have statistical signifi cance (P
ABSTRACT
0.05).(4) The subtypes of 4 cases of B-cell lymphoma diagnosed by cytology originally were determined by analyzing immunophenotype of their bone marrow involvement.Conclusions:Flow cytometry is an effective method for detecting bone marrow involvement in B-cell lymphoma and is superior to cytomorphology;Bone marrow involvement detected by FCM can be useful for helping diagnosis.The relevance of bone marrow involvement in different types of untreated B-cell lymphoma patients with clinical presentations and response to treatment should be further studied in more patients.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the clinicopathologic features of CD30-positive sinusoidal large B-cell lymphoma (CD30 + SLBCL) and its relative correlation with Epstein-Barr virus (EBV).</p><p><b>METHODS</b>Two cases of CD30 + SLBCL, a 65-year-old men and a 85-year-old women were morphologically and immunophenotypically analyzed. EBV status was also evaluated through not only the polymerase chain reaction (PCR) amplification to the EBV Bam HIW DNA sequence, but also an immunohistochemical detection of the latent membrane protein 1 (LMP1).</p><p><b>RESULTS</b>The patients presented with similarly superficial lymphadenopathy. One of them died of the tumor within 10 months. Microscopically, both of the neoplasms were characterized by a cohesive sinus growth pattern and the monomorphic cytology of the tumor cells. Immunohistochemically, They were both positive for CD45, CD30, and CD20 or CD79alpha, whereas neither expressed EMA, ALK1, nor any histiocytic/T-lineage markers. No evidence of EBV-infection could be found either.</p><p><b>CONCLUSIONS</b>CD30 + SLBCL is a morphologically and immunophenotypically distinctive variant of diffuse large B-cell lymphoma, which should be distinguished from T/null cell type anaplastic large cell lymphoma and some other nodal lesions with a predominantly sinusoidal infiltrative pattern. CD30 + SLBCL may not be correlation with EBV.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Diagnosis, Differential , Immunohistochemistry , Ki-1 Antigen , Lymphoma, B-Cell , Diagnosis , Pathology , Lymphoma, Large-Cell, Anaplastic , Diagnosis , PathologyABSTRACT
<p><b>OBJECTIVE</b>To study the genetic basis of aberrant crypt foci (ACF), which serve as a very early morphological alteration during the development of carcinogenesis by analyzing the loss of heterozygosity (LOH).</p><p><b>METHODS</b>DNA from 35 colorectal carcinomas (CRC) and 34 matched ACF were isolated by microdissection. LOH of microsatellite loci at 18q12, 18q21, 5q12, 5q21, 3p21, 2p16, 17q21, 17q11 and 11p13 was detected by means of ABI-SEQUENCER and GeneScan software was applied for analysis.</p><p><b>RESULTS</b>The rate of LOH in ACF (41.18%) was less than that in carcinoma (68.57%) (P < 0.05). The profile of LOH rates at loci 18q12, 5q12, 3p21, 17q21, 17q11, 11p13 and 2p16 in ACF was similar to that in carcinoma. The LOH frequencies on 18q12, 18q21, 5q12, 5q21, and 3p21 were higher than that on 17q11 and 11p13. However the rate at 18q21 and 5q21 in ACF was much lower than that in the carcinoma (P < 0.05). The co-existing carcinomas displayed more polypoid growth pattern and located more at the sigmoid colon and rectum. LOH in carcinomas did not correlate with the location, size, type of the carcinoma and Duke's stage.</p><p><b>CONCLUSIONS</b>ACF are putative preneoplastic lesions that might represent the earliest morphological lesion with the alteration at molecular genetic level. Our study provides further genetic evidence in the pathogenesis of colorectal carcinomas.</p>
Subject(s)
Humans , Chromosomes , Chromosomes, Human, Pair 11 , Chromosomes, Human, Pair 17 , Chromosomes, Human, Pair 18 , Chromosomes, Human, Pair 2 , Chromosomes, Human, Pair 3 , Chromosomes, Human, Pair 5 , Colorectal Neoplasms , Genetics , Pathology , Loss of Heterozygosity , Precancerous ConditionsABSTRACT
<p><b>OBJECTIVE</b>To assess the feasibility of detecting SYT-SSX fusion transcripts in paraffin-embedded tissues of synovial sarcoma by reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>METHODS</b>RT-PCR was used to amplify the SYT-SSX fusion transcripts using archival formalin-fixed paraffin-embedded tumor specimens from a series of 37 synovial sarcoma cases. To investigate the specificity of the SYT-SSX fusion transcripts, a variety of non-synovial sarcoma tumors were included in the study as negative controls. The detected messages derived from fusion genes were confirmed by subsequent sequence analysis.</p><p><b>RESULTS</b>SYT-SSX fusion transcripts were detected in 33 of 37 (89.2%) synovial sarcomas. None of the 34 cases of non-synovial sarcoma tumors showed amplified products of SYT-SSX fusion transcripts, although PBGD mRNA was detected in all specimens. Among 33 SYT-SSX-positive synovial sarcomas, 22 tumors had an SYT-SSX 1 fusion transcript, whereas 6 tumors had an SYT-SSX2 fusion transcript. Fusion types can not be distinguished in the remaining 5 cases. There was a significant relationship between SYT-SSX fusion type and histologic subtype. All 10 biphasic synovial sarcomas had the SYT-SSX1 fusion, whereas all tumors with SYT-SSX2 were of monophasic morphology (P < 0.05).</p><p><b>CONCLUSIONS</b>RT-PCR can be applied to archival formalin-fixed paraffin-embedded tumor tissues as a sensitive and reliable technique for the diagnosis and differential diagnosis of synovial sarcoma. There is an association between SYT-SSX fusion type and histological subtype. SYT-SSX2 fusion transcripts can only be found in monophasic synovial sarcoma.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Oncogene Proteins, Fusion , Genetics , Paraffin Embedding , RNA, Messenger , Reverse Transcriptase Polymerase Chain Reaction , Sarcoma, Synovial , Genetics , PathologyABSTRACT
WTBZ]Breast cancer resistance protein (BCRP) is a recently discovered half-transporter belonging to the ABC transporter superfamily as P-glycoprotein(P-gp) and multiple resistance protein (MRP). The latest research results concerned BCRP on construction features of gene, relationship to differentiation of hemopoietic stem cell and correlated transport substrates were reviewed in the article and it's clinical significance was mentioned at the same time.
ABSTRACT
Objective To identify the chemoresistant factors predicting the response to preoperative chemotherapy and clinicopathological prognosis in bulky cervical cancer. Methods 68 patients with bulky cervical carcinoma treated with two courses of intraarterial infusion of cisplatin 80mg, 5 fluorouracil(5Fu) 1500mg and AT 1258 or EADR 60mg, followed by radical hysterectomy and pelvic lymphnodenectomy at our hospital between 1996-1999 were retrospectively reviewed. Expressions of the chemoresistance related proteins, such as P glycoprotein glutathione S transferase ?(GST ?), and proliferating cell nuclear antigen(PCNA) in the tumor cells were examined by immunohistochemistry in previous biopsy specimens. These results were compared with the chemotherapeutic response obtained by gynecological examination and vagina ultrasonic. 68 patients were followed up. SPSS 8.0 was used. Results P glycoprotein expression rate was 31% and GST ? expressioin rate was 51%. There were 38 patients whose PCNA labellings were more than 50% and 30 less than 50%. The total chemotherapeutic response rate was 84%. Chemotherapeutic response rate was significantly correlated with P glycoprotein expression( P =0.013) and PCNA labelling ( P =0.001), but not GST ? expression in the tumor cells. Parautrial involvement and lymph node metastasis were independent factors for prognosis in this group. The survival rate in MDR(+) group was lower than MDR(-) group. No significant correlation between eigher the expression of GST ? or PCNA. Conclusions The expression of P glycoprotein and PCNA is potentially useful for predicting the response to preoperative chemotherapy for cervical cancer. The parautrial involvement and lymph node metastasis were independent prognostic factors for the survival rate including. the expression of P glycoprotein.
ABSTRACT
Objective To explore clinical features and prognosis of patients with hereditary nonpolypnsis colorectal cancer(HNPCC).Methods Twenty-four kindreds of Chinese HNPCC according to Amsterdam standard were enrolled and their pedigree trees were drawn.Clinicopathological and follow- up data were collected,clinical features and prognosis of 24 kindreds of Chinese HNPCC were analyzed as well.Results Among 24 H NPCCkindreds,there were 116 cases of cancer including 16 cases of multiple cancers in probands and 9 cases of multiple cancers in the members of kindreds.The age of patients ranged from 19 to 74.Of all the patients,there were 120 loci of colorectal cancers and 32 foci of HNPCC related extracolonic cancers.Among probands of 24 HNPCC kindreds,the average incidence age of onset- ring first colorectal cancer was 42.5,the male and right-side colon cancer patiens were more than female and left-side colon cancer patiens,respectively.The most pathologic type was tubular adenocarcinomas with moderately differentiation,which accounted for 45.8%(11/24).Up to the deadline of follow-up, 14 cases had survived for more than 5 years accounting for 58.3%(14/24) Of them,9 cases survived for more than 10 years and 1 case survived for 27 years.Conclusions Chinese patients with HNPCC have special characteristics such as moderately differentiated tubular adenocarcinomas,early onset of coloreetal cancer,right-side colon involvement.
ABSTRACT
Objective To study the clinicopathological characteristics of hereditary nonpolyposis colorectal cancer (HNPCC) in Chinese population with different criteria and guidelines. Methods Twenty four families fulfilling Amsterdam Criteria (AC), 15 additional families fulfilling Japanese Criteria (JC) and the remaining 19 patients fitting Bethesda Guidelines (BG) were analyzed. Results In the 24 AC families there were 116 malignant tumor patients including 90 colorectal cancer (CRC) subjects and in the 15 JC families there were 54 malignant tumor patients including 33 CRC cases. The two groups displayed similar clinical features. Mean age of first CRC at diagnosis was 46.1 and 51.4 years old, respectively. The proximal colonic cancers accounted for 55.4% versus 44.8%. Synchronous and metachronous multiple CRCs occurred in 25.6% and 18.2% of patients respectively. Totally there were 55 extracolonic tumors in the two groups. Gastric and endometrial carcinomas were two most common extracolonic tumor types in our series. The tumors of the 34 probands showed more frequent exophytic growth pattern, higher occurance of poorly differentiated carcinoma, A / B Dukes stage and more Crohn's like lymphoid reaction ( P
ABSTRACT
Objective To evaluate the correlation between vascular endothelial growth factor(VEGF) expression and microvessel density(MVD) in gastric carcinoma (GC) and the relationship of VEGF and MVD with clinicopathologic characteristics and prognosis of GC. Methods The expression of VEGF and intratumoral microvessel density (MVD) in one hundred and sixteen resected specimens of the patients with GC were observed and counted, and the relationship of VEGF and MVD with clinicopathologic factors and prognosis of GC were analysed. Results The expression of VEGF was found in 60.34% of the specimens. The MVD value was much higher in VEGF(+) group than that in VEGF(-) group (26.16±8.50 and 19.22±8.20, respectively, P<0.01). Expression of VEGF was significantly higher in patients with lymph node metastasis than that in patients without lymph node metastasis (p<0.05).Expression of VEGF was highly correlated with the stage of tumor (P<0.05). MVD correlated with lymph node metastasis (P<0.01) and abdomen metastasis (P<0.01) and increased with the TNM stage (P<0.01). The total five-year survival rate in VEGF(-) group and low MVD group were significantly higher than that in VEGF(+) group and high MVD group respectively(both P<0.01). Multivariate analysis indicated that the expression of VEGF and MVD were independent prognostic factors of GC. Conclusions The expression of VEGF and MVD can reflect the malignant degree of GC. They may serve as the prognostic factors and guide the decisions on the therapy.
ABSTRACT
Mucosa-associated lymphoid tissue lymphomas are a distinct subgroup of non-Hodgin's lymphoma with a particular clinicopathologic behavior.It is the most common type of extranodal low-grade B cell lymphoma.This type of lymphoma tends to appear in patients with a history of autoimmune disease or chronic inflammatory disorders.These indolent lesions usually remain localized for long periods and often respond to local therapy.The most common site of MALT lymphoma is the stomach.This article reviews clinical features and management of MALT lymphoma,emphasizing on gastric MALT lymphoma.
ABSTRACT
Purpose:To evaluate the relationship between the expressions of MDR and GST-? and the response to neoadjuvant chemotherapy and prognosis in cervical carcinoma. Methods:The expressions of MDR and GST-? were examined by Envision immunohistochemistry using pretreatment biopsy specimens. The stage distribution of 57 patients in the study was 7 stage Ib, 35 stage IIa, 15 stage IIb. Treatment consisted of 2 courses of neoadjuvant chemotherapy followed by radical hysterectomy and lymphonectomy. If the patient was found to have parametrial involvement, pelvic lymph node metastasis, microscopic tumor emboli or disease in vagina stemp, she was given adjuvant radiotherapy after operation. All patients were followed up and the median follow-up time was 35 months (21-66 months). Statistical method used was SPSS 8.0 package. Results:There were 14 patients with cervical carcinoma who had expression of MDR. The rate of expression of MDR was 24.6% (14/57). Also there were 29 patients who had expression of GST-?. The rate of expression was 50.8% (29/57). The total response rate of neoadjuvant chemotherapy was 81%. The complete clinical response rate was 19% (11/57) and partial response rate was 61% (35/57). All patients were treated by operation following chemotherapy and 13 patients were given adjuvant radiotherapy after operation. The 5-year survival rate in stage Ib was 100%, stage IIa 90% and stage IIb 78.5%. The results showed the expression of MDR was related to response of neoadjuvant chemotherapy and 5-year survival. It is 93%(40/43) in group of MDR(-) and 43%(6/14) in group of MDR(+)( P =0.001). But it was not related to FIGO, histopathologic, parametrial involvement, and pelvic lymph nodes metastasis. The expression with GST-? only related to response of chemotherapy. The response rate in the group with expression of GST-? is 69% and it is 93% in the group with GST-?(-)( P =0.02).Conclusions:The response rate of neoadjuvant chemotherapy in group of MDR(-) and GST-?(-) was better than in the group with expression of MDR and GST-?. The measure of MDR and GST-? is helpful to predict the response of neoadjuvant chemotherapy in cervical cancer and MDR may related to prognosis of cervical cancer.