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1.
Int J Oncol ; 12(4): 883-8, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9499450

ABSTRACT

Early gastric cancers (EGC) may be subdivided into 2 groups by means of the use of mitotic index, apoptotic index and cell density: EGCs with high cell turnover and low cell density, which show high cell dissociation and, more frequently, lymph node invasion; EGCs with low cell turnover and high cell density. The same parameters discriminate among intestinal type tumors, when separately considered from diffuse ones. No correlation is noted of these 2 groups with transforming growth factor-alpha, epidermal growth factor receptor and p53 expression, gross type, entity of neoangiogenesis, and submucosal invasion.


Subject(s)
Stomach Neoplasms/pathology , Apoptosis , Cell Count , Humans , Mitosis , Proliferating Cell Nuclear Antigen/analysis
2.
Int J Cancer ; 74(6): 637-41, 1997 Dec 19.
Article in English | MEDLINE | ID: mdl-9421362

ABSTRACT

Mitotic (MI) and apoptotic index (AI), the sum of the 2, i.e., the turnover index (TI), tumor neovascularization (NV) and p53 expression, as well as tumor grading and node status, are evaluated in early and advanced gastric-cancer cases. T1 cases show significantly less frequent lymph-node invasion and lower tumor grade, and, taken together, have significantly lower MI, Al and TI and higher values of NV than the T2-3 cases. However, correlation of the variables shows that the above-mentioned discrimination is due to a minority of T1 cases (11 out of 33), while the majority of them are allocated in the same 95% ellipse of tolerance of the T2-3 cases.


Subject(s)
Neovascularization, Pathologic/pathology , Stomach Neoplasms/blood supply , Stomach Neoplasms/pathology , Azure Stains , Cell Cycle/physiology , Cell Death/physiology , Cell Division/physiology , DNA, Neoplasm/analysis , Humans , Intestines/pathology , Lymphatic Metastasis , Neoplasm Invasiveness , Neoplasm Staging , Reproducibility of Results , Staining and Labeling/methods , Tumor Suppressor Protein p53/biosynthesis
3.
Eur J Cancer Prev ; 5(4): 287-95, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8894566

ABSTRACT

Previous histochemical studies have shown that changes occur in the composition of mucins both in preneoplastic and neoplastic lesions of the gastric mucosa. Since monoclonal antibodies are now available which recognize the protein product of distinct mucin genes, they are likely to provide useful tools for evaluating these changes. Thus, a monoclonal antibody 996/1 raised against a peptide epitope of the colonic mucin MUC2 was examined for its potential as a prognostic indicator in gastric cancer. 996/1 works well on formalin-fixed paraffin sections and shows good staining of the colonic goblet cells in the region of the golgi, while there is no staining of normal control gastric mucosa. The epitope was detected in all cases of intestinal metaplasia (44 samples) and some but not all cases of dysplasia (26 samples) and gastric carcinoma (74 samples). There was no significant difference between the positivity of the tumours according to their classification, stage and lymph node status. These results unfortunately gave little indication that this antibody would be a useful prognostic tool in gastric cancer. However, the pattern of 996/1 staining provides useful information about the molecular changes in mucin expression that occur in gastric carcinogenesis.


Subject(s)
Biomarkers, Tumor/analysis , Epitopes/analysis , Mucins/analysis , Neoplasm Proteins/analysis , Precancerous Conditions/chemistry , Stomach Neoplasms/chemistry , Antibodies, Monoclonal , Biomarkers, Tumor/immunology , Gastric Mucosa/chemistry , Gastric Mucosa/pathology , Humans , Immunohistochemistry , Mucin-2 , Mucins/immunology , Neoplasm Proteins/immunology , Peptides/analysis , Precancerous Conditions/pathology , Stomach Neoplasms/pathology
4.
Gut ; 38(2): 299-301, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8801216

ABSTRACT

A case is presented of Churg-Strauss syndrome in a young man in whom the definitive diagnostic procedure was a full thickness sigmoidoscopic rectal biopsy, with submucosal sampling. Gastrointestinal changes in Churg-Strauss syndrome, a rare systemic illness characterised by asthma, blood and tissue eosinophilia, vasculitis, and granulomatous inflammation are common but poorly reported. The endoscopic and histopathological features of a case are described and emphasise the potential value of a limited sigmoidoscopy in establishing the diagnosis, when lower gastrointestinal symptoms are present.


Subject(s)
Churg-Strauss Syndrome/pathology , Rectal Diseases/pathology , Adult , Biopsy , Humans , Male , Sigmoid Diseases/pathology , Sigmoidoscopy/methods
5.
Int J Cancer ; 62(2): 149-54, 1995 Jul 17.
Article in English | MEDLINE | ID: mdl-7622288

ABSTRACT

Gastric dysplasia (high-grade, HGD, and low-grade, LGD) and normal mucosa were tested for anti-p53, anti-Ki-67 and anti-PCNA monoclonal antibodies on paraffin sections, and for relative AgNOR area and number on semithin Epon-Araldite sections. The proliferative compartment in normal mucosa was restricted to the middle layer corresponding to the neck-isthmus region. In LGD and HGD there was an expansion of this compartment to the lower and upper layers of mucosa, and in HGD in particular to the upper layer. p53 was always negative in LGD as well as in normal mucosa, while it was positive in 34 out of 51 cases of HGD. The most discriminant variables between LGD and HGD were relative AgNOR area and the percentages of MIB-1, p53 and PCNA. In p53-positive HGD the highest percentages of PCNA and MIB-1 were in the middle and upper layers (PCNA) or the upper layer (MIB-1), while in p53-negative HGD cases cell proliferation was maximal in the middle layer, although also present in the upper layer. The majority of cases of LGD did not demonstrate cell proliferation in the upper layer, but 5 cases behaved similarly to the p53-negative HGD cases. No significant correlations were found among percentages of MIB-1 and of PCNA and relative AgNOR area and number.


Subject(s)
Gastric Mucosa/metabolism , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Stomach Diseases/genetics , Stomach Diseases/pathology , Adenocarcinoma/pathology , Antibodies, Monoclonal , Cell Division , Discriminant Analysis , Genes, p53 , Humans , Ki-67 Antigen , Neoplasm Proteins/genetics , Nuclear Proteins/genetics , Nucleolus Organizer Region/ultrastructure , Proliferating Cell Nuclear Antigen/genetics , Stomach Neoplasms/pathology
6.
Br J Cancer ; 71(1): 30-6, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7819044

ABSTRACT

Epidermal growth factor (EGF), its related peptide transforming growth factor (TGF-alpha) and their common receptor (EGFR) have been implicated in the control of cell proliferation and differentiation in the gastrointestinal epithelium and may play an important role in gastric carcinogenesis. We compared the immunohistochemical expression and topographic distribution of these peptides using Western blot analysis in gastric carcinoma precursor lesions and in non-cancer tissue. We observed: (i) increased and extended expression of TGF-alpha in normal mucosa and hyperplasia in carcinoma fields compared with non-cancer controls; (ii) increased expression of EGFR in intestinal metaplasia (IM) from carcinoma fields compared with controls; (iii) EGF expression was not detected in normal mucosa and only weakly in IM; (iv) coexpression of TGF-alpha/EGFR and EGF/EGFR was higher in intestinal metaplasia in carcinoma fields than in non-cancer controls. We conclude that altered expression of TGF-alpha/EGFR is associated with morphological changes during gastric carcinogenesis. In this regard increased expression of TGF-alpha is a very early event which is subsequently followed by up-regulation of EGFR and this has important biological and clinical implications.


Subject(s)
Epidermal Growth Factor/analysis , ErbB Receptors/analysis , Precancerous Conditions/chemistry , Stomach Neoplasms/chemistry , Transforming Growth Factor alpha/analysis , Humans , Immunohistochemistry , Precancerous Conditions/pathology , Stomach Neoplasms/pathology
7.
Int J Cancer ; 60(1): 27-32, 1995 Jan 03.
Article in English | MEDLINE | ID: mdl-7814148

ABSTRACT

Adenocarcinomas of the gastro-esophageal junction (GEJ) and those arising in Barrett's esophagus (BE) are increasing in the West and have a poorer prognosis than distal stomach cancers. This has been attributed mainly to anatomical location, but biological factors such as growth-regulatory molecules have been implicated. We have investigated the expression of one of these factors, TGF alpha, and its precursor prepro TGF alpha in 82 adenocarcinomas of GEJ (32 resected specimens and 50 biopsies) as well as in 48 BE biopsies without tumor, by immunohistochemistry and by Western-blot analysis. TGF alpha staining was shown in the cytoplasm and membrane of cells. Western blot confirmed that most immunoreactivity was against mature TGF alpha (5.6 kDa), but higher-molecular-weight bands were also identifiable, suggesting some reactivity with prepro protein. TGF alpha expression was more extense and intense in intestinal metaplasia and cancer. The tubular histological type of adenocarcinoma was more often positive than the signet-ring type. Primary tumors with lymph-node metastases also had increased TGF alpha expression. We conclude, therefore, that there is differential regulation of the expression of TGF alpha and its precursors during esophageal tumorigenesis.


Subject(s)
Barrett Esophagus/metabolism , Barrett Esophagus/pathology , Protein Precursors/analysis , Transforming Growth Factor alpha/analysis , Adenocarcinoma/chemistry , Adenocarcinoma/pathology , Blotting, Western , Epithelium/chemistry , Epithelium/pathology , Esophageal Neoplasms/chemistry , Esophageal Neoplasms/pathology , Gastric Fundus , Gastric Mucosa/chemistry , Humans , Immunohistochemistry , Intestinal Mucosa/chemistry , Lymphatic Metastasis , Myocardium/chemistry
9.
Gut ; 35(12): 1697-700, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7829004

ABSTRACT

Abnormalities of the tumour suppressor gene p53 have been shown in approximately 60% of advanced gastric adenocarcinomas and it has been suggested that the immunohistochemical finding of increased p53 expression is a prognostic marker in gastric cancer. No studies of early (T1) tumours have been reported. Over expression of p53 protein in 95 early gastric carcinomas and in adjacent mucosa was investigated using immunohistochemistry with antibody CM1. Thirty five per cent of the tumours were positive. The frequency of p53 positivity in tumours of tubular histological type (46%) was significantly higher than that in signet ring tumours (10%) (p = 0.006), and neoplasms that invaded deeply into the submucosa were more frequently positive (45%) than others (30%). Five of eight (62%) T1 tumours with lymph node metastases showed immunoreactive p53. In signet ring tumours, immunopositivity correlated with the frequency of DNA aneuploidy. p53 Over expression was also found in 15% of 26 examples of high grade dysplasia in mucosa adjacent to invasive tumours. No positivity was found in intestinal metaplasia or in normal mucosa. The findings show that immunocytochemically demonstrable over expression of p53 correlates with other morphological markers of aggressiveness in T1 gastric adenocarcinoma. The increasing frequency of p53 immunoreactivity in the sequence of high grade dysplasia-->early gastric cancer-->advanced gastric cancer supports the view that abnormalities of p53 are related to tumour progression in gastric carcinogenesis.


Subject(s)
Genes, p53 , Precancerous Conditions/genetics , Stomach Neoplasms/genetics , Tumor Suppressor Protein p53/biosynthesis , Adenocarcinoma/genetics , Gastric Mucosa/metabolism , Gene Expression Regulation, Neoplastic , Genetic Markers , Humans , Immunohistochemistry , Lymphatic Metastasis , Stomach Neoplasms/metabolism
10.
Anal Cell Pathol ; 7(1): 1-9, 1994 Jul.
Article in English | MEDLINE | ID: mdl-7981132

ABSTRACT

The DNA content of 48 gastric carcinomas from archival material was analysed by static and flow cytometry. By image analysis 81.3% of the tumours were aneuploid and ploidy was related to stage (P = 0.024) and lymph node metastasis. A trend for better survival (> 12 months) was observed in patients with diploid tumours (P = 0.058). The mean 5c exceeding rate (5cER) was significantly related to tumour stage (P < 0.05) and patient's survival (P = 0.018). In contrast, by flow cytometry only 43.7% of these tumours were aneuploid and these were more often associated with lymph node metastasis (59.3%) but no relationship was observed with any other parameters or patient's survival. In this series, image analysis appears to be more sensitive than flow cytometry in detecting small aneuploid populations. It may give additional prognostic information. It is, however, a time-consuming technique.


Subject(s)
Aneuploidy , Carcinoma/genetics , DNA, Neoplasm/analysis , Stomach Neoplasms/genetics , Carcinoma/mortality , Flow Cytometry , Humans , Image Processing, Computer-Assisted , Stomach Neoplasms/mortality
11.
J Pathol ; 173(3): 221-6, 1994 Jul.
Article in English | MEDLINE | ID: mdl-7931842

ABSTRACT

Barrett's oesophagus has a well-recognized association with oesophageal adenocarcinoma, with phenotypic progression through dysplasia to malignancy. The nuclear phosphoprotein p53 is a putative tumour suppressor with mutations resulting in both loss of negative growth regulatory function and possible gain of oncogene function. Many mutant forms have a prolonged half-life and are demonstrable with immunohistochemical techniques. We examined 62 endoscopic oesophageal biopsies and 36 oesophageal resections for p53 overexpression using the monoclonal antibody DO-7 on paraffin-embedded tissue. The series included 40 cases of Barrett's metaplasia, 13 cases of dysplasia, and 81 cases of adenocarcinoma. None of the cases of metaplasia was p53-positive, compared with 4/13 cases of dysplasia and 52/81 cases of adenocarcinoma. There was no association between the degree of dysplasia and p53 expression, although a trend emerged of increasing p53 expression with higher tumour grade. We conclude that p53 overexpression is frequent in oesophageal adenocarcinoma and may be related to tumour grade. p53 overexpression is not restricted to neoplastic lesions and mutation of this tumour suppressor may occur early in the malignant progression of Barrett's oesophagus.


Subject(s)
Adenocarcinoma/chemistry , Antibodies, Monoclonal , Barrett Esophagus/metabolism , Esophageal Neoplasms/chemistry , Esophagus/chemistry , Tumor Suppressor Protein p53/analysis , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Cell Nucleus/chemistry , Esophageal Neoplasms/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Precancerous Conditions/chemistry
12.
Int J Cancer ; 57(3): 324-9, 1994 May 01.
Article in English | MEDLINE | ID: mdl-8168991

ABSTRACT

Between 1967 and 1976, 1,525 Slovenian patients with a histological diagnosis of intestinal metaplasia (IM) were classified according to subtype of IM based on morphology and mucin staining; 518 cases were diagnosed with type I, 197 with type II and 275 with type III, but in 291 the diagnosis of IM was not confirmed. Patients who had developed cancer or died up to 1986 were identified by record linkage at the Slovenia Cancer Registry and the Central Population Registry in Slovenia. A total of 34 incident cases of gastric cancer occurring at least 6 months after the diagnosis of IM were identified. The standardised incidence ratio (SIR) for stomach cancer was 2.23 in the whole cohort. It was highest for IM type III, followed by type II and IM-unconfirmed, but not increased for type I. The relative risk (RR) of developing gastric cancer based on Cox's proportional hazards model was 2.14 for type II and 4.58 for type III, compared with type I. The RR was especially increased for a subgroup of type III secreting sulphomucins in their goblet cells in comparison with types I-II negative to sulphomucins. Our results confirm that subtyping of IM is useful for identifying individuals at high risk for gastric cancer.


Subject(s)
Intestines/pathology , Stomach Neoplasms/epidemiology , Adult , Aged , Cohort Studies , Female , Humans , Incidence , Male , Metaplasia/epidemiology , Metaplasia/pathology , Middle Aged , Risk Factors , Slovenia/epidemiology
13.
Gut ; 35(5): 604-7, 1994 May.
Article in English | MEDLINE | ID: mdl-8200550

ABSTRACT

The induction of adenocarcinomas in the glandular stomach of the adult male Wistar rat by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was used as a model to study the expression of the growth promoting peptide, transforming growth factor alpha (TGF alpha), during experimental gastric carcinogenesis. TGF alpha was identified using the monoclonal antibody Ab-2 and standard immunohistochemistry, together with a semiquantitative assessment of the intensity of expression. Immunoreactivity was confined to the differentiated compartment of the mucosa while the carcinogen MNNG caused a significant increase in the intensity of TGF alpha expression (p < 0.01), after as little as 16 weeks' exposure. In experimental adenocarcinomas, a change to a previously undescribed pattern of perinuclear TGF alpha expression was found, which may represent the site of intense TGF alpha production in the Golgi apparatus after malignant transformation.


Subject(s)
Adenocarcinoma/chemistry , Precancerous Conditions/chemistry , Stomach Neoplasms/chemistry , Transforming Growth Factor alpha/analysis , Adenocarcinoma/chemically induced , Animals , Immunohistochemistry , Intestinal Mucosa/chemistry , Male , Methylnitronitrosoguanidine , Precancerous Conditions/chemically induced , Rats , Rats, Wistar , Stomach Neoplasms/chemically induced
14.
Histochem J ; 25(12): 843-53, 1993 Dec.
Article in English | MEDLINE | ID: mdl-7906685

ABSTRACT

This review provides an update on proliferation-associated antibodies applicable to immunohistochemical techniques in formalin-fixed paraffin-embedded tissue. New insights into proliferating cell nuclear antigen (PCNA) and antibodies to PCNA are presented. The characterization of the protein recognized by the Ki-67 antibody has enabled production of a new range of antibodies (monoclonal and polyclonal) which have immunostaining profiles similar to those of the original antibody. A new proliferation-associated antibody, KiS1, is described. The clinical applications of antibodies to PCNA in human material are summarized, and the limitations of these studies are discussed.


Subject(s)
Antibodies, Monoclonal , Antigens, Neoplasm/analysis , Biomarkers/analysis , Cell Division , Neoplasm Proteins/analysis , Nuclear Proteins/analysis , Animals , Antigens, Neoplasm/immunology , Biomarkers, Tumor/analysis , DNA Topoisomerases, Type II , DNA-Binding Proteins , Humans , Immunohistochemistry , Ki-67 Antigen , Neoplasm Proteins/immunology , Nuclear Proteins/immunology , Poly-ADP-Ribose Binding Proteins , Proliferating Cell Nuclear Antigen
16.
Int J Cancer ; 55(4): 598-603, 1993 Oct 21.
Article in English | MEDLINE | ID: mdl-8406987

ABSTRACT

Abnormalities affecting tumour suppressor genes on chromosome 5q21 are increasingly recognised as important in the pathogenesis of a variety of human cancers, particularly of the gastrointestinal tract. We have examined a series of gastric and pancreatic cancers from European patients for loss of heterozygosity (LOH) of markers within and around the APC and MCC genes on chromosome 5q21 using restriction fragment length polymorphism and polymerase chain reaction techniques. We find that LOH of the APC and MCC genes is particularly frequent in gastric cancers of diffuse type, but very infrequent in pancreatic cancers. We have also used single-strand conformational polymorphism to screen for abnormalities of the sequence of the APC and MCC genes in a panel of pancreatic cancer cell lines. Our results suggest that there are distinct differences in the molecular pathogenesis of gastric and pancreatic cancer and that abnormalities of APC and MCC may be involved particularly in the diffuse type of gastric cancer.


Subject(s)
Adenocarcinoma/genetics , Carcinoma/genetics , Chromosome Deletion , Chromosomes, Human, Pair 5 , Genes, Tumor Suppressor , Pancreatic Neoplasms/genetics , Stomach Neoplasms/genetics , Humans , Mutation , Polymerase Chain Reaction , Polymorphism, Genetic , Tumor Cells, Cultured
17.
Int J Cancer ; 54(6): 935-40, 1993 Jul 30.
Article in English | MEDLINE | ID: mdl-8335401

ABSTRACT

The pattern of c-erbB-3 gene product was studied in 91 advanced gastric carcinomas, adjacent hyperplastic mucosa, intestinal metaplasia and dysplasia and in normal controls, using immunohistochemistry in archival material. All tumours showed positive c-erbB-3 staining in both cytoplasm and membrane. No significant differences of expression were observed between intestinal and diffuse-type carcinomas or any other clinical parameters. Of interest is the expression in the adjacent mucosa, which is extensive, cytoplasmic, and of lower intensity than in the tumours. Further studies are currently being carried out to clarify the role of this protein in tumour behaviour and gastric carcinogenesis.


Subject(s)
Proto-Oncogene Proteins/analysis , Stomach Neoplasms/chemistry , Adult , Aged , Aged, 80 and over , Cell Membrane/chemistry , Cytoplasm/chemistry , Female , Gastric Mucosa/chemistry , Humans , Male , Middle Aged , Receptor, ErbB-3
19.
Histopathology ; 22(4): 349-54, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8099897

ABSTRACT

Immunohistochemistry using the PC10 antibody to proliferating cell nuclear antigen (PCNA) was applied to archival material from mucosa adjacent to gastric carcinoma ('normal', hyperplasia, complete and incomplete intestinal metaplasia and dysplasia) and non-cancer controls (normal and complete intestinal metaplasia). Overall, increased PCNA indices, with expansion and altered location of the proliferative zones, were observed in carcinoma fields and compared with controls (P < 0.001). These differences were particularly significant in 'normal' mucosa far from carcinoma as compared with normal in controls (P < 0.001). In carcinoma 'fields' distinct patterns of PCNA expression were noted in complete and incomplete intestinal metaplasia. Similarly, in dysplastic lesions high PCNA indices were present either throughout the gland or found predominantly in the upper compartment. We conclude that these differences in PCNA index and staining patterns might prove useful in monitoring the evolution of the disease in the follow-up of patients at risk of developing gastric cancer.


Subject(s)
Antigens, Neoplasm/analysis , Nuclear Proteins/analysis , Precancerous Conditions/pathology , Stomach Neoplasms/pathology , Antibodies, Monoclonal , Humans , Immunoenzyme Techniques , Precancerous Conditions/immunology , Proliferating Cell Nuclear Antigen , Stomach Neoplasms/immunology
20.
Gut ; 34(2): 230-4, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8432479

ABSTRACT

DNA ploidy of 100 early gastric carcinomas (T1) was analysed by flow cytometry on archival material from five European centres and was correlated to morphological features and clinical behaviour. Tumours were classified according to the macroscopic appearance, histological type, and growth pattern. Aneuploidy was observed in 39% of tumours. Aneuploidy was more frequent in submucosal than in mucosal tumours (p = 0.04), in raised than in flat or ulcerated lesions (p = 0.001), and in the intestinal histological than in the diffuse types (p = 0.016). The presence of lymph node metastasis in 10 cases had no obvious relation to DNA ploidy. Five related deaths occurred during the follow up (6 months--16 years) of 84 patients. These results are similar to those reported in a large Japanese series suggesting no major differences between the two populations. Although follow up data were insufficient to relate DNA ploidy to tumour behaviour in this study, the Japanese experience shows that particular attention should be paid to early direction and complete surgical excision of raised intestinal type T1 carcinomas that have a Pen A growth pattern and are aneuploid.


Subject(s)
DNA, Neoplasm/analysis , Ploidies , Stomach Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Female , Flow Cytometry , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , S Phase , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology
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