Adenocarcinoma ; metabolism ; pathology ; Adenocarcinoma, Mucinous ; metabolism ; pathology ; Adenocarcinoma, Papillary ; metabolism ; pathology ; Carcinoma, Signet Ring Cell ; metabolism ; pathology ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Organic Cation Transport Proteins ; biosynthesis ; genetics ; Organic Cation Transporter 2 ; Osteopontin ; Prognosis ; RNA, Messenger ; biosynthesis ; genetics ; Sialoglycoproteins ; biosynthesis ; genetics ; Stomach Neoplasms ; metabolism ; pathology ; Survival Rate

Adenocarcinoma ; pathology ; Adult ; Aged ; Female ; Humans ; Lasers ; Male ; Middle Aged ; Neuroendocrine Cells ; pathology ; Polymerase Chain Reaction ; methods ; Stomach Neoplasms ; pathology

OBJECTIVE: To ivestigate the incidence of neuroendocrine (NE) cells and hormone products in adenocarcinomas and to explore its clinicopathological significance. METHODS: 356 cases of adenocarcinomas were studied by immunocytochemistry with antibodies for chromorgranin and polypeptide hormones. RESULTS: The prevalence of NE cells and hormone products were detected in 54 of 130(41.5%) and 32 of 54 (59.3%) colorectal carcinomas, 38 of 96(39.6%) and 14 of 38 (36.8%) gastric cancer, 8 of 21(38.1%) and 4 of 8(50.0%) prostatic carcinomas, 17 of 81(21.0%) and 3 of 17(17.6%) breast cancer, 5 of 28(17.9%) and 3 of 5 (60.0%) pancreatic carcinomas, respectively. Among carcinomas of large intestine, pancreas and breast, the incidence of NE cells in well differentiated ones was higher than that in the poorly differentiation. By contrast, NE cells were found more frequently in the letter than in the former in gastric carcinoma. The cases with NE cell (++) or polypeptide positive cells exhibited higher 5-year survival rate than those without NE cells in colorectal carcinomas. CONCLUSION: The presence of neuroendocrine cells and the hormone products may be close correlated with the degree of tumore cell differentiation. For colorectal carcinoms, there is a close correlation of the presence of NE cells and the hormone products with the tumor staging and prognosis.

OBJECTIVETo investigate the status of Notch signaling pathway in small cell lung cancer (SCLC).

METHODSExpression plasmids of pEFBOS-NIC-MYC and pEFBOS-neo were transfected into NCI-H446 cells. Stably transfected cell lines were selected and their growth rates were examined by MTT method. Expression of downstream genes along the Notch signaling pathway were studied by RT-PCR. Protein expression of euroendocrine markers of CgA and NSE were detected by Western blot analysis and immunocytochemistry.

RESULTSThe expression of HES1 was increased in the pEFBOS-NIC-MYC group, but the expression of hASH in the pEFBOS-NIC-MYC group was decreased significantly. The transfected cells with pEFBOS-NIC-MYC plasmid showed a significantly slower growth rate compared with that of two control groups (P < 0.05, Student's t-test). Immunocytochemistry of NSE showed that PUs in the NIC transfected group, sham group and negative control group were 7.21 ± 0.59, 28.25 ± 1.46, 30.57 ± 1.31 respectively, the former one was smaller than the values of the latter two significantly (P < 0.01). Western blot analysis showed the grave scales of CgA in NIC transfected group and sham group to be 0.54 ± 0.03 and 0.99 ± 0.05 respectively (grave scales of the negative control was set as 1.00), the former one significantly smaller than that of the other two groups (P < 0.01). The grave scales of NSE in the NIC transfected group and sham group were 0.43 ± 0.02 and 1.07 ± 0.09 respectively (grave scales of the negative control was set as 1.00) and the former one was significantly smaller than the other two groups (P < 0.01).

CONCLUSIONNotch signaling pathway regulates SCLC cells through its inhibitory effect on hASH1 transcription via HES1 along with an expression inhibition of neuroendocrine markers in SCLC.

Basic Helix-Loop-Helix Transcription Factors ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Chromogranin A ; metabolism ; Homeodomain Proteins ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Phosphopyruvate Hydratase ; metabolism ; Plasmids ; Receptor, Notch1 ; metabolism ; physiology ; Recombinant Proteins ; metabolism ; Signal Transduction ; Small Cell Lung Carcinoma ; metabolism ; pathology ; Transcription Factor HES-1 ; Transfection

BACKGROUNDThe aim of this study was to investigate DNA content and expression of c-erbB-2, PS2, and prostate-specific antigen (PSA) proteins in breast carcinomas with neuroendocrine (NE) cell differentiation.

METHODSChromogranin, c-erbB-2, PS2, and PSA in 131 samples of breast cancer were detected immunohistochemically. Classic Feulgen staining image analysis techniques were used to quantify DNA content in 81 of the breast cancer samples.

RESULTSThe c-erbB-2 positive rate in breast carcinoma samples containing neuroendocrine cells was 37.5% and the rate of high expression of c-erbB-2 (++ or +++) was 33.3%, both significantly lower than that in breast carcinomas without neuroendocrine cells (62.6% and 68.7%, respectively, P < 0.05). The rates of positive PS2 and PSA expression in breast carcinoma samples containing neuroendocrine cells were 72.2% and 55.0%, respectively, both significantly higher than that in breast carcinoma samples without neuroendocrine cells (45.0% and 16.4%, respectively, P < 0.05). In NE(+) samples, the integral optical density, DNA index, DNA stemline peak, > 5 c aneuploidy cells, and rate of aneuploidy among cells were all lower than that in NE(-) breast carcinomas (P < 0.01). In NE(+) grade I or II breast carcinomas, these indices were also all lower than that in the NE(-) breast carcinoma samples (P < 0.01).

CONCLUSIONBreast carcinomas with neuroendocrine differentiation have a lower rate of malignancy. Neuroendocrine differentiation could serve as a prognostic marker in clinical practice.

Breast Neoplasms ; chemistry ; pathology ; Cell Differentiation ; DNA ; analysis ; Female ; Humans ; Membrane Proteins ; analysis ; Neurosecretory Systems ; cytology ; Presenilin-2 ; Prostate-Specific Antigen ; analysis ; Receptor, ErbB-2 ; analysis

Computer Graphics ; Computer-Assisted Instruction ; Forensic Pathology ; Humans ; Imaging, Three-Dimensional ; Pathology ; education ; Pathology, Clinical ; Specimen Handling ; methods

OBJECTIVETo investigate the incidence and clinicopathologic significance of MSI and LOH on 3P in breast carcinoma and its precancerous lesions, intraductal papillary adenoma and ductal carcinoma in situ.

METHODS41 paired sporadic invasive breast carcinomas, 13 archival precancerous lesion specimens of the breast and 14 couples of benign hyperplasia were collected. Twelve microsatellites on chromosomes 2p, 3p, 5q, 6q, 16q, 17q, eleven markers on chromosome 3p were amplified for MSI and LOH, respectively, by polymerase chain reaction ( PCR ) with designed primers and detecting after polyacrylamide gel electrophoresis. In addition, the expression of protein of hMSH2, hMLHI, FHIT, ER, and PR were detected by immunohistochemistry.

RESULTSMSI was observed, at least two microsatellite markers, in 15 out of 41 (36. 6%) of the carcinomas, almost all belonging to poorly or intermediately differentiated carcinoma. Instability was shown in 9 of the 13 cases of precancerous lesions, but only 2 among them had more than 2 MSI sites. There was no MSI in benign hyperplasia. MSI was targeted predominately at D3S1766, D2S2739 in both carcinomas and precancerous lesions. Of the 11 loci examined, D3S1295, D3S1029 and D3S1038 were identified as the locus with most frequent LOH which were all correlated significantly with some clinicopathological parameters such as histological type, lymph node metastasis in breast cancer, while D3S1295 and D3S1029 were the most frequent markers in precancerous lesions. LOH of D3S1295 had significant correlation with negative expression of FHIT. Positive expression of hMLH1 and hMSH2 protein was detected in breast carcinomas in scattered distribution and their positive rate was 45% and 40% , respectively. In precancerous lesions, hMLH1 and hMSH2 protein showed diffuse expression and their positive rate was 61. 54% and 76. 92% , respectively, significantly lower than that in the control tissues.

CONCLUSIONDefective expression of MMR genes is closely associated with the development of breast cancer. Genomic instability might play a role in the early stage during multi-step mammary carcinogenesis. MSI indicates poor histological differentiation in breast carcinoma. D3S1766 and D2S2739 might be the sensitive sites to detect MSI in breast carcinoma and precancerous lesions. The smallest common LOH deletion regions seem likely to be situated between 3p14 and 3p25, indicating the existence of breast tumor related genes in those regions and some of them might affect tumor development.

Acid Anhydride Hydrolases ; metabolism ; Adaptor Proteins, Signal Transducing ; metabolism ; Adenoma ; genetics ; metabolism ; pathology ; Adult ; Aged ; Breast ; metabolism ; pathology ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; Chromosome Deletion ; Chromosomes, Human, Pair 3 ; genetics ; DNA Mismatch Repair ; Female ; Humans ; Hyperplasia ; Immunohistochemistry ; Loss of Heterozygosity ; Lymphatic Metastasis ; Microsatellite Instability ; Middle Aged ; MutL Protein Homolog 1 ; MutL Proteins ; Neoplasm Proteins ; metabolism ; Neoplasm Staging ; Nuclear Proteins ; metabolism ; Polymerase Chain Reaction ; Precancerous Conditions ; genetics ; metabolism ; pathology ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo investigate the mRNA expression of bFGF and MMP-9 in gastric carcinomas and to find their correlation with tumor microvascular density (MVD), invasion, metastasis and patients survival.

METHODSIn situ hybridization and immunohistochemistry technique were used to test the expression of bFGF mRNA and MMP-9 mRNA and protein of CD34 in 105 specimens of gastric carcinoma.

RESULTSIn situ hybridization revealed that the positive rates of bFGF mRNA and MMP-9 mRNA were 60.95 and 58.1%, respectively; The mean MVD (46.09 +/- 11.52, 43.75 +/- 13.41 piece/0.72 mm(2)) in tumors with bFGF mRNA and MMP-9 mRNA positive expression was significantly higher than that (29.41 +/- 12.47; 33.45 +/- 13.92 piece/0.72 mm(2)) in tumors with their negative expression, respectively; The positive expression rates of bFGF and MMP-9 mRNA were correlated to invasion depth (r(s) = 0.211, P = 0.031; r(s) = 0.335, P = 0.001, respectively), growing pattern (r(s) = 0.324, P = 0.001; r(s) = 0.267, P = 0.006, respectively), vessel invasion (r(s) = 0.579, P = 0.001; r(s) = 0.209, P = 0.032, respectively), lymph node metastasis (r(s) = 0.405, P = 0.001; r(s) = 0.343, P = 0.001, respectively) and distant metastasis (r(s) = 0.474, P = 0.001; r(s) = 0.468, P = 0.001, respectively), but not correlated to tumor type (r(s) = 0.134, P = 0.173; r(s) = 0.103, P = 0.145, respectively) and differentiation (r(s) = 0.096, P = 0.332; r(s) = 0.102, P = 0.298, respectively); And then, the mean MVD in tumors with infiltrating type, stage T(3)-T(4), vessel invasion, lymph node metastasis and distant metastasis was significantly higher than that in tumors with expanding type (t = 10.105, P = 0.001), stage T(1)-T(2) (t = 5.961, P = 0.001), non-vessel invasion (t = 7.394, P = 0.001), non-lymph node metastasis (t = 3.819, P = 0.01) and non-distant metastasis (r = 10.578, P = 0.001); There was a positive relationship between MVD and bFGF mRNA and MMP-9 mRNA (t = 3.207, P = 0.002; t = 7.035, P = 0.001), respectively; the mean survival time in cases with positive bFGF mRNA and MMP-9 mRNA and MVD value >/= 39.5 was significantly shorter than that in cases with their negative expression and MVD value < 39.5.

CONCLUSIONSbFGF and MMP-9 promote angiogenesis in gastric cancer. Test of the expression of bFGF and MMP-9 may act as an useful index to determine angiogenesis, invasion, metastasis and patients survival.

Adult ; Aged ; Biomarkers, Tumor ; biosynthesis ; genetics ; Female ; Fibroblast Growth Factor 2 ; biosynthesis ; genetics ; Humans ; In Situ Hybridization ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; RNA, Messenger ; biosynthesis ; Stomach Neoplasms ; metabolism ; mortality ; pathology ; Survival Rate

OBJECTIVETo investigate the expression of CD147 and E-cadherin in gastric carcinoma and their correlation with clinicopathological features.

METHODSThe expression of CD147 and E-cadherin in gastric cancer tissue chip (TC) was detected by in situ hybridization (ISH) and immunohistochemistry in 220 cases of gastric carcinoma and 31 cases with normal gastric mucosa.

RESULTSThe expression rates of CD147 mRNA, E-cadherin mRNA and E-cadherin protein were 50.5%, 17.7% and 15.5%, respectively. The CD147 expression was negatively correlated with E-cadherin expression. There was a significant relationship between CD147 mRNA expression and tumor diameter, TNM stage, invasion depth, vessel invasion, lymph node and distant metastasis. The E-cadherin mRNA expression was closely related with TNM stage, invasion depth and vascular invasion. There was a significant relationship between E-cadherin protein expression and tumor diameter, TNM stage and vascular invasion. The mean survival time in cases with CD147-positive expression was shorter than that in negative cases, while E-cadherin was in an opposite relationship.

CONCLUSIONIn gastric carcinoma, up-regulation of CD147 and down-regulation of E-cadherin are in a negative correlation. The examination of both these two factors together is useful for predicting the invasion and metastasis of gastric cancer, therefore, can be used as a significant marker to direct clinic therapy and estimation of prognosis.

Adenocarcinoma ; metabolism ; pathology ; Adenocarcinoma, Mucinous ; metabolism ; pathology ; Adenocarcinoma, Papillary ; metabolism ; pathology ; Basigin ; genetics ; metabolism ; Biomarkers, Tumor ; metabolism ; Cadherins ; genetics ; metabolism ; Carcinoma, Signet Ring Cell ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Staging ; RNA, Messenger ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Survival Rate ; Tumor Burden

OBJECTIVETo investigate the effects of Notch1 signal activation on proliferation and neuroendocrine marker expression in small cell lung cancer cells.

METHODSThe active form of Notch1 (NIC) was over-expressed in NCI-H446 cells by constitutive transfection and a stable transfected cell line was established. Proliferation of NCI-H446 cells was analysed by MTT assay on 6 successive days. Expression of neuroendocrine markers (CgA, NSE) was observed by immunohistochemistry and Western blot analysis. Statistical analysis was conducted to compare the results in cells with NIC transfected and those in control groups.

RESULTSMTT assay showed that absorbance (A) of cells overexpressing Notch1 was significantly depressed compared with that of the control cells (P<0.05). Immunohistochemistry of CgA showed that PUs in the NIC transfected group, sham group and negative control group were 8.81 +/- 0.77, 38.10 +/- 1.55, 38.97 +/- 0.80, respectively, the former one was significantly smaller than that of the latter two (P<0.01). Immunohistochemistry of NSE showed that PUs in the NIC transfected group, sham group and negative control group were 7.21 +/- 0.59, 28.25 +/- 1.46, 30.57 +/- 1.31, respectively, the former one was significantly smaller than that in the latter two (P<0.01). Western blot analysis showed that the gray scales of CgA in the NIC transfected group and sham group were 0.54 +/- 0.03 and 0.99 +/- 0.05, respectively, (gray scale of the negative control set as 1.00), the former one was significantly smaller than that of the other two groups (P<0.01). The gray scales of NSE in the NIC transfected group and sham group were 0.43 +/- 0.02 and 1.07 +/- 0.09, respectively (gray scale of the negative control set as 1.00), the former one was significantly smaller than that of the other two groups (P<0.01).

CONCLUSIONNotch1 may behave as a tumor suppressor in small cell lung cancer. Notch1 signal activation can inhibit the proliferation and neuroendocrine marker expression in small cell lung cancer cells, suggesting that Notch1 gene could be a new target for small cell lung cancer treatment and probable relief of paraneoplastic syndrome.

Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; Chromogranin A ; metabolism ; Humans ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; pathology ; Phosphopyruvate Hydratase ; metabolism ; Receptor, Notch1 ; genetics ; metabolism ; physiology ; Recombinant Proteins ; genetics ; metabolism ; Small Cell Lung Carcinoma ; metabolism ; pathology ; Transfection