Animals ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms ; metabolism ; secondary ; Lymphatic Metastasis ; Neoplasm Proteins ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; Protein Tyrosine Phosphatases ; metabolism ; Stomach Neoplasms ; metabolism ; pathology

Apoptosis ; Colonic Neoplasms ; metabolism ; pathology ; HT29 Cells ; Humans ; Insulin-Like Growth Factor Binding Proteins ; metabolism

BACKGROUND/AIMS: Obesity increases the risk of colorectal cancer and adenomatous polyp, and one of the underlying mechanisms of this increase is considered to be due to the growth promoting effects of adipokines, such as leptin. In order to investigate this finding, leptin expression in the colonic tissue and blood leptin concentration of the colonic adenoma patients were compared to those of the control group. METHODS: Colonic adenoma tissues were obtained by polypectomy (n=60). In these patients, normal colonic mucosa at remote areas from the polyp was also obtained and blood samples were collected as well. Age and sex matched control subjects were selected among those who showed normal colonic mucosa in health screening colonoscopy (n=60). RESULTS: There was no significant difference in serum leptin concentration between the colonic adenoma patients and control subjects. Leptin expression was noted in 43.3% of the colonic adenomas, but only in 6.7% of normal colonic mucosa from the control subjects (p<0.01). There were ten cases of concurrent adenocarcinoma in situ in adenoma patients, eight cases of which expressed leptin (p=0.01). In adenoma group, leptin expression rate was significantly high in larger adenomas and in obese patients (p<0.05). However, there was no statistically significant relationship between leptin expression in colonic mucosa and serum leptin level. CONCLUSIONS: Leptin expression was more frequently observed in colonic adenomas, especially in larger adenomas associated with adenocarcinoma in situ, but blood leptin level was not related to tissue leptin expression. Leptin expression was more frequently observed in obese patients from the adenoma group. Therefore, leptin may play an important role in colonic tumorigenesis and progression, especially in obese patient.
Adenoma/metabolism/*pathology ; Adult ; Aged ; Body Mass Index ; Colonic Neoplasms/metabolism/*pathology ; Colonic Polyps/metabolism/pathology ; Female ; Humans ; Intestinal Mucosa/*metabolism ; Leptin/blood/*metabolism ; Male ; Middle Aged ; Obesity/metabolism/pathology ; Odds Ratio ; Waist Circumference

BACKGROUND/AIMS: Obesity increases the risk of colorectal cancer and adenomatous polyp, and one of the underlying mechanisms of this increase is considered to be due to the growth promoting effects of adipokines, such as leptin. In order to investigate this finding, leptin expression in the colonic tissue and blood leptin concentration of the colonic adenoma patients were compared to those of the control group. METHODS: Colonic adenoma tissues were obtained by polypectomy (n=60). In these patients, normal colonic mucosa at remote areas from the polyp was also obtained and blood samples were collected as well. Age and sex matched control subjects were selected among those who showed normal colonic mucosa in health screening colonoscopy (n=60). RESULTS: There was no significant difference in serum leptin concentration between the colonic adenoma patients and control subjects. Leptin expression was noted in 43.3% of the colonic adenomas, but only in 6.7% of normal colonic mucosa from the control subjects (p<0.01). There were ten cases of concurrent adenocarcinoma in situ in adenoma patients, eight cases of which expressed leptin (p=0.01). In adenoma group, leptin expression rate was significantly high in larger adenomas and in obese patients (p<0.05). However, there was no statistically significant relationship between leptin expression in colonic mucosa and serum leptin level. CONCLUSIONS: Leptin expression was more frequently observed in colonic adenomas, especially in larger adenomas associated with adenocarcinoma in situ, but blood leptin level was not related to tissue leptin expression. Leptin expression was more frequently observed in obese patients from the adenoma group. Therefore, leptin may play an important role in colonic tumorigenesis and progression, especially in obese patient.
Adenoma/metabolism/*pathology ; Adult ; Aged ; Body Mass Index ; Colonic Neoplasms/metabolism/*pathology ; Colonic Polyps/metabolism/pathology ; Female ; Humans ; Intestinal Mucosa/*metabolism ; Leptin/blood/*metabolism ; Male ; Middle Aged ; Obesity/metabolism/pathology ; Odds Ratio ; Waist Circumference

OBJECTIVETo study the morphologic and immunohistochemical features of gastrointestinal stromal tumors (GISTs) and to explore the reference parameters for malignancy.

METHODSSeventy six (76) cases of primary GISTs were distinguished from a group of gastrointestinal mesenchymal tumors by use of a panel of antibodies such as CD117, CD34 by immunohistochemical EnVision method, their biologic behaviors were analyzed by including their follow-up data.

RESULTSAll patients were adults, age range 32 to 81 years (mean 54 year), male 39 cases and female 37 cases; the tumors were situated in stomach (36 cases), in small intestine (23 cases), colon (2 cases) and rectum (15 cases). The most common symptoms were abdomen mass, vague pain and GI bleeding. Forty eight (48) cases were mainly located within the muscularis propria, 25 cases outside the serosa, and 3 cases below the mucosa. Grossly, they were of soft consistency often with hemorrhage, cystification or necrosis. Microscopically, the tumors were composed of spindle cells (46 cases) or epithelioid cells (9 cases) and of both cells (21 cases), arranged in interlacing fasicles, diffusing sheets, pallisading, whirling, alveolar and giant pseudo-rosette shapes. Tumor cells often had abundant cytoplasm with light to moderate eosinophilic or slight basophilic in staining, the nuclei generally showed spindle, blunted ends, round or signet in shape with nucleoli. Immunohistochemically, CD117 and CD34 showed diffuse strong expression, the positive rates were 98.7% and 68.4% respectively, alpha-SMA, MSA, S-100, PGP9.5 showed focal expression, the positive rates were 25.0%, 19.7%, 23.7% and 17.1% respectively, vimentin were all positive and desmin, GFAP, NF were all negative. Nine cases were benign, 19 cases borderline and 48 cases malignant. Follow-up of 20 cases with benign and borderline tumors found patients alive without tumor. In the malignant group of 34 cases, 10 cases were alive without tumor, 10 cases developed recurrence or metastasis, and 14 cases died of tumor. Coagulative necrosis, mitotic activity over 10/50HPF, high cellularity and obvious pleomorphism were all in the malignant group. In this group, tumor necrosis, adhesion in operation, tumor, over 5 cm in diameter, mitotic activity over 5/50HPF had significant differences among three groups and the 3 years survival rate had a significant difference in tumors with or without coagulative necrosis and also in tumors with or without mitotic activity over 5/50HPF.

CONCLUSIONSGISTs predominantly occurred in middle aged or old patients, the tumors had varied cell types and different arrangements, the immunohistochemical characters were positive for CD117 and CD34, negative for desmin, occasional positive for alpha-SMA, MSA, S-100 and PGP9.5, which were helpful to differentiate GIST from leiomyomas and Schwannomas. Coagulative necrosis, mitotic activity over 10/50HPF, high cellularity with obvious pleomorphism were also helpful parameters for diagnosis of malignancy aside from metastasis and invasion. Adhesion, over 5 cm in diameter and mitotic activity over 5/50HPF but less than 10/50HPF might be the potential malignant parameters.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Gastrointestinal Neoplasms ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Intestinal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Rectal Neoplasms ; metabolism ; pathology ; Statistics as Topic ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo explore cytological parameters that may identify the primary sites of metastatic adenocarcinomas in serous fluid.

METHODSSerous fluid specimens from 89 cases of metastatic adenocarcinomas (40 metastatic adenocarcinomas of lung, 6 metastatic adenocarcinomas of breast, 21 metastatic ovary adenocarcinomas, 22 metastatic gastrointestinal and pancreatic adenocarcinomas) were studied by using multiple morphologic parameters. Immunocytochemical S-P method was used to detect the expression of CA125, CA199, SPB and TTF-1 in 75 cases.

RESULTSMetastatic adenocarcinomas of different primary sites displayed certain different morphologic features, including the total amount of tumor cells, size of clusters, ratio of clusters over single cells, configuration of tumor clusters and the background of the smear. Cell clusters of small to medium sizes represented 95% and 100% in the metastatic adenocarcinomas of lung and breast, respectively. Most of the ovarian metastatic adenocarcinomas (85.7%) presented some large cell clusters and larger amount of cells, whereas certain metastatic gastrointestinal and pancreatic adenocarcinomas (45.5%) presented smaller number of cells and predominantly to be single cell in distribution (40.9%). Psammoma bodies were found in metastatic adenocarcinomas of lung and ovary. SPB and TTF-1 expression supported the diagnosis of adenocarcinoma of pulmonary origin. CA125 expression supported an ovarian origin. Although CA199 was seen in all groups of metastatic adenocarcinomas, nevertheless, its appearance in tumor cells in ascitic fluid specimens supported gastrointestinal and pancreatic origins.

CONCLUSIONMorpho-logic features of the cytological smear, immunohistochemical staining and clinical history are equally important in determining the primary sites of metastatic adenocarcinomas in serous fluid.

Adenocarcinoma ; metabolism ; secondary ; Ascitic Fluid ; metabolism ; pathology ; Breast Neoplasms ; metabolism ; pathology ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Male ; Nuclear Proteins ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; Pancreatic Neoplasms ; metabolism ; pathology ; Pleural Effusion, Malignant ; metabolism ; pathology ; Proteins ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism

Adenocarcinoma ; metabolism ; pathology ; Chromogranin A ; metabolism ; Colonic Neoplasms ; metabolism ; pathology ; Humans ; Immunohistochemistry ; methods ; Proliferating Cell Nuclear Antigen ; metabolism ; Staining and Labeling ; methods ; Vimentin ; metabolism

Adenocarcinoma ; metabolism ; pathology ; Adenoma ; metabolism ; pathology ; Colonic Neoplasms ; metabolism ; pathology ; Cytoplasm ; metabolism ; Female ; HSP27 Heat-Shock Proteins ; Heat-Shock Proteins ; analysis ; Humans ; Intestinal Mucosa ; metabolism ; pathology ; Male ; Neoplasm Proteins ; analysis ; Proteome ; analysis ; Proteomics ; methods ; Rectal Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the clinicopathological characteristics and expression status of Ki67, p53, CEA, CDX, CK7 in colorectal sessile serrated adenoma (SSA).

METHODSThe clinicopathological data of 11 cases of SSA, 51 cases of hyperplastic polyp (HP) and one case with mixed HP/SSA were reviewed and analyzed retrospectively. The expression of Ki67, p53, CEA, CDX and CK7 were detected by immunohistochemistry.

RESULTSThe major histological features in SSA were architectural abnormality in crypts, dilatation of serrated crypt bases like an inverted "T" or "L" shape adjacent to muscularis mucosa. Atypical cells containing round to oval nuclei and nucleoli were also observed. The immunohistochemical staining showed that the expression of p53 increased gradually from HP to TA: 11.8% in HP, 20.0% in SSA, 41.2% in VTA and 75.0% in TA, with a significant difference among the groups (chi(2) = 17.996, P = 0.000). However, no significant difference in the expression of CDX and CK7 was observed between HP and SSA. Of the 10 SSA cases, positive expression of Ki67 was found in cells located in the base or middle part of crypt in 6 cases, positive cells index was 26% - 50% in 5 cases, and > 50% in 3. Compared with the expression of Ki67 in the HP, VTA and VA, SSA showed a significant difference in both the positive cell number and in the positive regions. (positive number: chi(2) = 34.601, P = 0.000; positive regions: chi(2) = 63.077, P = 0.000).

CONCLUSIONMorphological diagnosis of SSA was mainly based on crypt architectural and cellular abnormalities, and the crypt architectural abnormality may be more important than cellular features. Detection of p53 and Ki67 expression may be helpful in differential diagnosis and understanding the nature of SSA.

Adenoma ; metabolism ; pathology ; Adenoma, Villous ; metabolism ; pathology ; Adult ; Aged ; CDX2 Transcription Factor ; Carcinoembryonic Antigen ; metabolism ; Colonic Neoplasms ; metabolism ; pathology ; Colonic Polyps ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Homeodomain Proteins ; metabolism ; Humans ; Immunohistochemistry ; Keratin-7 ; metabolism ; Ki-67 Antigen ; metabolism ; Male ; Middle Aged ; Rectal Neoplasms ; metabolism ; pathology ; Retrospective Studies ; Trans-Activators ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVESTo study the change of ability to transform from 5'-deoxy-fluorouracil monophosphate (5'-DFUR) to fluorouracil (5-FU) in human colon cancer cell lines SW480 and LOVO which transfected with thymidine phosphorylase (TP) gene. And to discuss the anti-cancer activity of 5'-DFUR to SW480 and LOVO cells.

METHODSTP cDNA were transfected into human colorectal cancer cell lines SW480 and LOVO with the lentiviral vector, pLenti6.3_MCS_IRES2-EGFP. The transfection efficiency was analyzed by flow cytometer, the mRNA expression of TP was detected by RT-PCR, and the TP protein expression was detected by Western blot, and the volumes of 5-FU converted from 5'-DFUR both in 2 cells and medium were detected by high performance liquid chromatography (HPLC). The 50% inhibitory concentration (IC50) of 5'-DFUR on these 2 colon cancer cell lines both wild type and TP-transfected cells were evaluated by MTT assay.

RESULTSThe colorectal cancer cell lines SW480 and LOVO transfected with human TP cDNA were monitored 5 generations, and the transfections efficiency rate wea about 95%. Compared with wild type cell SW480 and LOVO, the RQ values of mRNA expression of SW480-TP and LOVO-TP were (695 ± 171) folds (t = -7.00, P = 0.002) and (282 ± 87) folds (t = -5.61, P = 0.030), respectively. Also TP protein expression in SW480-TP and LOVO-TP were higher than their parent cells shown by Western blot. The volume of 5-FU converted from 5'-DFUR in the medium cultured SW480-TP and LOVO-TP were increased compared with their parent cells, respectively (t = 19.406-66.921, P < 0.01), whereas few of 5-FU was detected both in wild, and TP-transfected cells. After transfected with TP cDNA, the IC50 of 5'-DFUR on SW480-TP and LOVO-TP were (587 ± 17) µmol/L and (1088 ± 89) µmol/L respectively, and there were significantly less than their parent cells (t = -32.59 and -8.52, P < 0.01).

CONCLUSIONSThe stabilized transfections of SW480 and LOVO with higher TP expression could be built with lentiviral vector. Transfected TP cDNA into SW480 and LOVO, could improve the expression both of TP mRNA and TP protein, increase the volume of 5-FU converted from 5'-DFUR in medium, and result in an enhancement of anticancer effect on these 2 cells.

Cell Line, Tumor ; Colonic Neoplasms ; pathology ; Floxuridine ; metabolism ; Fluorouracil ; metabolism ; Humans ; Thymidine Phosphorylase ; genetics ; Transcription, Genetic ; Transfection