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1.
Zheng HC Takahashi H Li XH Hara T Masuda S Guan YF Takano Y 《Virchows Archiv : an international journal of pathology》2008,452(2):147-155
Parafibromin is a protein encoded by the hyperparathyroidism 2 oncosuppressor gene and its downregulated expression is involved
in pathogenesis of parathyroid carcinomas. To clarify the roles of parafibromin expression in tumourigenesis and progression
of gastric carcinomas, it was examined by immunohistochemistry (IHC) on tissue microarray containing gastric carcinomas (n = 508), adenomas (n = 45) and gastritis (n = 49) with a comparison of its expression with clinicopathological parametres of carcinomas. Gastric carcinoma cell lines
(MKN28, AGS, MKN45, KATO-III and HGC-27) were studied for parafibromin expression by IHC and western blot. Parafibromin expression
was localised in the nucleus of gastric epithelial cells, adenoma, carcinoma cells and cell lines. Its expression was gradually
decreased from gastritis to gastric carcinoma, through gastric adenomas (p < 0.05) and inversely correlated with tumour size, depth of invasion, lymphatic invasion, lymph node metastasis and Union
Internationale Contre le Cancer (UICC) staging (p < 0.05) but not with sex or venous invasion (p > 0.05). Parafibromin was strongly expressed in older carcinoma patients compared with younger ones (p < 0.05). There was stronger positivity of parafibromin in intestinal-type than diffuse-type carcinomas (p < 0.05). Univariate analysis indicated cumulative survival rate of patients with positive parafibromin expression to be higher
than without its expression (p < 0.05). Multivariate analysis showed that age, tumour size, depth of invasion, lymphatic invasion, lymph node metastasis,
UICC staging and Lauren’s classification but not sex, venous invasion or parafibromin expression were independent prognostic
factors for carcinomas(p < 0.05). Downregulated parafibromin expression possibly contributed to pathogenesis, growth, invasion and metastasis of gastric
carcinomas. It was considered as a promising marker to indicate the aggressive behaviours and prognosis of gastric carcinomas. 相似文献
2.
Zheng HC Li XH Hara T Masuda S Yang XH Guan YF Takano Y 《Virchows Archiv : an international journal of pathology》2008,452(5):525-534
To investigate the pathobiological behaviors of gastric mixed-type (MT) carcinomas and gastric carcinogenesis, the clinicopathological
characteristics of MT carcinomas were analyzed and compared with intestinal-type (IT) and diffuse-type (DT) carcinomas. The
expression of Ki-67, caspase-3, p53, fragile histine triad (FHIT), maspin, extracellular matrix metalloproteinase inducer
(EMMPRIN), vascular growth factor (VEGF), MUC-2, 4, 5AC and 6, CD44, E-cadherin, β-catenin, and phosphorylated glycogen synthase
kinase 3β-ser9 (P-GSK3β-ser9) was examined on tissue microarrays using immunohistochemistry. It was found that MT carcinomas exhibited large size, deep
invasion, frequent local invasion, and lymph node metastasis in comparison with IT and DT carcinomas (p < 0.05). All the markers except MUC-5AC showed higher expression in IT than DT carcinomas (p < 0.05). The expression of maspin, EMMPRIN, VEGF, MUC-4, and membrane E-cadherin was stronger in MT intestinal than diffuse
component (p < 0.05). Immunoreactivities to Ki-67, EMMPRIN, and VEGF were weaker in IT carcinoma than in the MT intestinal portion (p < 0.05), while the opposite was true for CD44, MUC-2, and MUC-6 (p < 0.05). The MT diffuse component displayed a higher expression of FHIT, VEGF, and P-GSK3β-ser9 than DT carcinoma (p < 0.05). The accumulative survival rate of the IT carcinoma patients was higher than the other types (p < 0.05). The invasive depth, venous invasion, lymph node, peritoneal or liver metastasis, and Lauren's classification were
independent prognostic factors for gastric carcinomas (p < 0.05). These findings suggested that MT carcinomas were also indicated to be more aggressive than IT and DT carcinomas.
Significant differences were observed in the proliferation, apoptosis, angiogenesis, mucin secretion, and cell adhesion between
IT and DT carcinomas, whereas only a few of these characteristics showed differences between the MT intestinal and diffuse
parts, thus suggesting that both the MT components might originate from the stem cells with similar genetic traits, but follow
different histogenic pathways. 相似文献
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4.
Fernández S Mosquera JL Alaña L Sanchez-Pla A Morote J Ramón Y Cajal S Reventós J de Torres I Paciucci R 《Virchows Archiv : an international journal of pathology》2011,458(3):323-330
The prostate tumor overexpressed-1 (PTOV1) protein was first described overexpressed in prostate cancer but not detected in
normal prostate. PTOV1 expression is associated to increased cancer proliferation in vivo and in vitro. In prostate biopsy,
PTOV1 detection is helpful in the early diagnosis of cancer. The purpose of this study was to analyze the relevance of PTOV1
expression to identify aggressive tumors derived from 12 different histological tissues. Tissue microarrays (TMAs) containing
182 biopsy samples, including 168 human tumors, were analyzed for PTOV1 and Ki67 expression by immunohistochemistry. Tumors
of low and high histological grade were selected from lung, breast, endometrium, pancreas liver, skin, ovary, colon, stomach,
kidney, bladder, and cerebral gliomas. One TMA with representative tissues without cancer (14 samples) was used as control.
PTOV1 expression was analyzed semiquantitatively for the intensity and percentage of positive cells. Ki67 was evaluated for
tumors proliferative index. Results show that PTOV1 was expressed in over 95% of tumors examined. Its expression was significantly
associated to high-grade tumors (p = 0.014). This association was most significant in urothelial bladder carcinomas (p = 0.026). Overall, the expression of Ki67 was associated to high-grade tumors, and it was significant in several tumor types.
PTOV1 and Ki67 were significantly co-overexpressed in all tumors (p = 0.001), and this association was significant in clear cell renal carcinoma (p = 0.005). In conclusion, PTOV1 expression is associated to more aggressive human carcinomas and more significantly to bladder
carcinomas suggesting that this protein is a potential new marker of aggressive disease in the latter tumors. 相似文献
5.
Goto A Hirahashi M Osada M Nakamura K Yao T Tsuneyoshi M Takayanagi R Oda Y 《Virchows Archiv : an international journal of pathology》2011,458(6):717-724
Although Helicobacter pylori is a risk factor for gastric cancer (GC), its detailed carcinogenesis remains unclear. Recently, aberrant expression of activation-induced
cytidine deaminase (AID) was demonstrated in gastric epithelium with H. pylori infection and seems to cause the accumulation of mutation. This investigation aims to elucidate whether or not AID expression
plays an important role in the carcinogenesis of early GC. We examined the correlation between immunohistochemical AID expression
and histological characteristics, including pre-existing chronic gastritis and cellular mucin phenotype in 138 cases of intramucosal
GC. Furthermore, we investigated the relationship between AID, p53 protein, and β-catenin. The low degree of polymorphonuclear
neutrophil activity, and the high degree of glandular atrophy and intestinal metaplasia were significantly correlated with
the high levels of AID expression in non-neoplastic mucosa (P = 0.007, P ≤ 0.001, and P = 0.003). With regard to mucin phenotype of carcinoma, the intestinal phenotype tended to have the higher AID expression
levels (P = 0.052). AID showed close correlations with Cdx2 and nuclear staining of β-catenin (P = 0.003, P = 0.034). As for p53 protein, no correlation was found with AID expression. Our findings suggest that aberrant AID expression
is correlated with persistent inflammatory condition induced by H. pylori infection and may contribute to the development of GC through an inflammatory condition and intestinalization. 相似文献
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7.
Miskad UA Semba S Kato H Matsukawa Y Kodama Y Mizuuchi E Maeda N Yanagihara K Yokozaki H 《Virchows Archiv : an international journal of pathology》2007,450(3):303-310
Phosphatase of regenerating liver (PRL)-3, encoding a 22-kD low molecular weight tyrosine phosphatase, has been reported to be associated with metastasis of colorectal
carcinoma. We assessed the levels of PRL-3 mRNA expression to know whether its up-regulation was involved in progression and metastasis of gastric carcinoma. Levels
of PRL-3 expression in 94 human gastric adenocarcinomas and 54 matched lymph node metastases were detected by in situ hybridization
and compared with clinicopathological characteristics including prognosis. High PRL-3 expression was detected in 36.2% of primary gastric carcinoma (with nodal metastasis, 55.6%; without nodal metastasis, 10%;
P < 0.001) and in 74.1% of lymph node metastases. The incidence of high PRL-3 expression in lymph node metastasis was significantly higher than in primary tumors (P < 0.044). Moreover, high expression of PRL-3 was closely associated with tumor size, lymphatic invasion, venous invasion, extent of lymph node metastasis, and tumor stage.
These results suggest that high PRL-3 expression may participate in the progression and metastasis of gastric carcinoma. PRL-3 might be a novel molecular marker for aggressive gastric cancer. 相似文献
8.
Brusegard K Stavnes HT Nymoen DA Flatmark K Trope CG Davidson B 《Virchows Archiv : an international journal of pathology》2012,460(2):193-202
Rab25, an epithelial-specific member of the Rab family of small GTPases, was previously shown to be overexpressed in ovarian/primary
peritoneal serous carcinoma compared to malignant mesothelioma using gene expression arrays. The objective of this study was
to validate this finding at the mRNA and protein level. Quantitative PCR analysis of 112 Müllerian serous carcinomas (84 effusions,
28 primary ovarian carcinomas) and 22 malignant mesotheliomas (19 effusions, 3 solid specimens) showed significantly higher
RAB25 mRNA expression in the former tumor (p < 0.001). Immunohistochemical analysis of Rab25 protein expression in 245 effusions showed significantly higher expression
of this protein in Müllerian serous carcinoma compared to malignant mesothelioma (189/209 vs. 12/36 positive tumors, respectively;
p < 0.001). Immunostaining of 101 patient-matched solid Müllerian carcinoma specimens (34 primary carcinomas, 67 metastases)
showed expression levels comparable to effusions (94/101 positive specimens; p > 0.05). Rab25 mRNA and protein expression levels in Müllerian carcinoma effusions did not correlate with overall or progression-free
survival. Our data confirm that Rab25 effectively differentiates Müllerian carcinomas from malignant mesothelioma at the mRNA
and protein level, suggesting a role in the diagnostic work-up of serosal cancers. 相似文献
9.
Kim HS Lee SH Won KY Kim GY Park YK Kim YW 《Virchows Archiv : an international journal of pathology》2012,460(1):61-68
Raf-1 kinase inhibitor protein (RKIP) has emerged as a significant metastatic suppressor in a variety of human malignancies.
We have recently demonstrated that reduced expression of RKIP is significantly associated with invasion and metastasis in
periampullary carcinomas, including pancreatic carcinoma, gallbladder carcinoma, and extrahepatic bile duct carcinoma. In
this study, we evaluated RKIP expression in ampulla of Vater (AoV) carcinoma and investigated its prognostic significance.
Immunostaining for RKIP was performed for 80 and 21 cases with primary and nodal metastatic AoV carcinoma, respectively. RKIP
expression was reduced in 32.5% (26/80) and 66.7% (14/21) of primary and nodal metastatic AoV carcinoma cases, respectively.
This distribution of RKIP expression was statistically significant (P < 0.001). The reduction in RKIP expression was significantly associated with the presence of nodal (P = 0.008) and distant (P = 0.002) metastases, a higher TNM stage group (P = 0.010), lymphatic invasion (P < 0.001), vascular invasion (P < 0.001), and a shorter disease-free survival (DFS; P = 0.028) and distant metastasis-free survival (DMFS; P = 0.005). In addition, reduced RKIP expression was an independent prognostic predictor for worse DFS and DMFS (P = 0.032 and P = 0.036, respectively). Our data suggest that a reduction in RKIP expression contributes to invasion and metastasis in AoV
carcinoma and is a significant prognostic marker in patients with AoV carcinoma. 相似文献
10.
Time-dependent expression of intestinal phenotype in signet ring cell carcinomas of the human stomach 总被引:5,自引:0,他引:5
Bamba M Sugihara H Kushima R Okada K Tsukashita S Horinouchi M Hattori T 《Virchows Archiv : an international journal of pathology》2001,438(1):49-56
Signet ring cell carcinomas of the stomach are thought to arise from the proper gastric mucosa without intestinal metaplasia. It was recently reported that intestinal phenotypes appear along with tumor progression. In this study, we performed several experiments to reconsider the significance of this intestinalization in the growth of signet ring cell carcinoma. We applied mucin histochemistry with monoclonal antibodies MUC2 (Ccp58) and M1 (45M1), and paradoxical concanavalin A staining for class III mucin [PCS(III)] reaction to 29 intramucosal and 25 deeply invasive carcinomas of this type and correlated the phenotypic expression with the size of the mucosal spread and the depth of tumor invasion. It was found that the larger the size of the mucosal lesion, the more frequently the intestinal phenotypes were demonstrated. There was no significant increase in the expression of the intestinal phenotype as the tumor invaded the deeper part of the mucosa or as the intestinal metaplasia increased in the background mucosa. The intestinal expression appeared to be suppressed in the earlier phase of deep invasion. In the mucosal part of the tumor, the intestinal phenotype was often expressed regionally and incompletely, coexisting with gastric phenotypes at the cellular and the tissue levels. These findings indicate that the expression of the intestinal phenotype is a time-dependent and unstable phenomenon probably based on the accumulation of genetic changes and plays a neutral role in progression of signet ring cell carcinomas. 相似文献
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12.
T. Yamachika Ken-ichi Inada Yasunobu Fujimitsu Shigeo Nakamura Yoshitaka Yamamura Tsuyoshi Kitou Steven H. Itzkowitz J. L. Werther Kazumasa Miki Masae Tatematsu 《Virchows Archiv : an international journal of pathology》1997,431(2):103-110
Recent developments in mucin histochemistry and immunohistochemistry have made reliable determination of the gastric and
intestinal phenotypes of gastric carcinoma cells possible. Phenotypic expression changes from gastric epithelial cell type
to intestinal epithelial cell type with the growth of gastric tumours in experimental animals. We studied cell differentiation
in gastric signet ring cell carcinomas with progression in 203 surgically obtained specimens. The results showed that the
proportion of gastric phenotype carcinomas, in which over 90% of the tissue consists of gastric epithelial cell type cells,
decreases with the depth of invasion. The proportion of mixed phenotype carcinomas (between 10% and 90% of the tissue made
up of gastric and/or intestinal epithelial cell type cells) increases. The intestinal phenotype (over 90% intestinal epithelial
cell type carcinoma cells) was found in four carcinomas (about 2%) involving the serosa. No clear relationship was evident
between phenotypic expression of carcinoma cells and the degree of intestinal metaplasia of the surrounding mucosa.
Progression of gastric signet ring cell carcinomas is associated with a phenotypic shift from gastric to intestinal type expression.
Received: 7 January 1997 / Accepted: 12 March 1997 相似文献
13.
Warner?Alpízar-Alpízar Martin?Illemann José?A.?Ramírez Adriana?Arias Wendy?Malespín-Benda?a Vanessa?Ramírez Leif?R.?Lund Niels?Borregaard Boye?Schnack?Nielsen 《Virchows Archiv : an international journal of pathology》2009,455(3):225-233
Helicobacter pylori infection is one of the most significant risk factors for gastric cancer. The infection is established early in life and
persists lifelong leading to a sustained chronic inflammation. Iron is essential for most living organisms. Bacteria use several
mechanisms to acquire iron from their hosts, including the synthesis of the potent iron chelators known as siderophores. Hosts
cells may express the siderophore-binding protein neutrophil gelatinase-associated lipocalin (NGAL/lipocalin-2 (Lcn2)) in
response to infection, thus preventing bacterial iron uptake. We have characterized here the pattern of expression of NGAL/Lcn2
in gastric mucosa (45 non-neoplastic and 38 neoplastic tissue samples) and explored the connection between NGAL/Lcn2 expression
and H. pylori infection. Immunohistochemical analysis showed high NGAL/Lcn2 expression in normal and gastritis-affected mucosa compared
to low expression in intestinal metaplasia, dysplasia, and gastric cancer. In normal and gastritis-affected mucosa (n = 36 tissue samples), NGAL/Lcn2 was more frequently seen in epithelial cells located at the neck and base of the glands in
H. pylori-positive cases than in similar epithelial cells of noninfected cases (Fisher’s exact test, p = 0.04). In conclusion, the high expression of NGAL/Lcn2 in normal and gastritis-affected mucosa infected with H. pylori suggests that NGAL/Lcn2 is upregulated locally in response to this bacterial infection. It is discussed whether this may
have a causal relation to the development of gastric cancer. 相似文献
14.
F. CARNEIRO L. SANTOS L. DAVID E. DABELSTEEN H. CLAUSEN M. SOBRINHO-SIMõES 《Histopathology》1994,24(2):105-113
In a previous report we suggested that T antigen appeared to be associated with gastric carcinoma. To verify this hypothesis and characterize the pattern of expression of simple-mucin type carbohydrate antigens (Tn. sialyl-Tn and T before and after neuraminidase) in normal gastric mucosa and precursor lesions of gastric carcinoma, we studied the mucosa adjacent to 100 cases of gastric carcinoma, gastric biopsies of 60 dyspeptic patients, eight adenomatous polyps and eight hyperplastic polyps. The expression of the antigens was more related to the cell type and underlying lesions than to the coexistence of carcinoma. The most distinctive findings concerned intestinal metaplasia, dysplasia and hyperplastic lesions. In intestinal metaplasia, Tn was found mostly in columnar cells and sialyl-Tn in goblet cells. T was more prevalent in incomplete intestinal metaplasia than in complete. A high prevalence of sialyl-Tn expression and cell membrane immunoreactivity for T antigen, similar to those previously found in gastric carcinomas, were observed in three adenomatous polyps, one hyperplastic polyp, five cases of adenomatous dysplasia in the neighbourhood of intestinal carcinomas and four cases of marked foveolar hyperplasia, three of which were from the mucosa adjacent to diffuse carcinomas. We conclude that adenomatous and hyperplastic lesions share with gastric carcinomas features of aberrant glycosylation, namely the cell membrane expression of T antigen. 相似文献
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Choschzick M Oosterwijk E Müller V Woelber L Simon R Moch H Tennstedt P 《Virchows Archiv : an international journal of pathology》2011,459(2):193-200
Carbonic anhydrase IX (CAIX) is a strictly membranous expressed metalloenzyme involved in cell adhesion, pH homeostasis, and
cancer progression. This study was designed to assess the role of CAIX in primary ovarian cancer. Two hundred five well-characterized
primary ovarian carcinomas were analyzed on a tissue microarray. CAIX expression was determined by immunohistochemistry using
a four-step scoring system. Moderate and strong membranous CAIX expression was found in 37 out of 205 (18%) of all assessable
ovarian cancer specimens. High levels of CAIX expression were related to mucinous and endometrioid phenotype of ovarian carcinomas
(p < 0.05). There was no association between CAIX overexpression and tumor stage, grading, and mitotic count of ovarian carcinomas
(p > 0.05). In univariate Cox regression analysis, advanced tumor stage (p < 0.01), high tumor grade (p = 0.017), high mitotic count (p = 0.025), and high CAIX expression levels (p = 0.031) were correlated to shorter overall patient survival. High pT stage (p = 0.036) and CAIX overexpression were connected to poor clinical outcome in endometrioid ovarian carcinomas. Multivariate
Cox regression hazard analysis comprising tumor stage, tumor grade, mitotic count, and CAIX expression revealed pT2/3 stage
and CAIX overexpression (scores 2 and 3) as independent prognostic markers in ovarian cancer (p < 0.01, each) as well as in the subgroup of endometrioid carcinomas (p < 0.05, each). In conclusion, CAIX is overexpressed in a substantial proportion of mucinous and endometrioid ovarian carcinomas
and connected to poor patient outcome. Our data support the potential therapeutic benefit of newly developed targeting antibodies
in advanced ovarian cancer. 相似文献
18.
Stefan Kommoss Dietmar Schmidt Friedrich Kommoss Juergen Hedderich Philipp Harter Jacobus Pfisterer Andreas du Bois 《Virchows Archiv : an international journal of pathology》2009,454(3):249-256
While there is no doubt that histologic grading is applicable in early stage ovarian carcinoma, it is still in controversial
discussion concerning advanced stage ovarian carcinoma. It was the aim of this study to assess the three most widely used
grading systems for ovarian carcinoma in terms of prognostic significance, concordance rates, and reproducibility in a large
number of advanced stage ovarian carcinomas of all types after standardized chemotherapy. Representative hematoxylin and eosin
slides from 334 cases of stage IIB–IV ovarian carcinoma (prospective randomized, multi-center, phase III study) were used.
The first round was grading of all cases according to FIGO, GOG, and Silverberg by one author. The second round (after 1 year)
was 30 randomly selected cases graded by three authors. None of the three grading systems was prognostically significant (FIGO
p = 0.38; GOG p = 0.70; Silverberg p = 0.92). The concordance rates between the three systems were as follows: FIGO/GOG 95.5%, κ = 0.929; Silverberg/FIGO 69.9%, κ = 0.533; Silverberg/GOG 66.8%, κ = 0,481. Grading of advanced stage ovarian carcinomas was of no value for estimation of prognosis in this homogeneously treated
patient group. Alternative methods should be defined, which might help to separate patients with high risk of tumor progression
from others with low risk. 相似文献
19.
Kim H Eun JW Lee H Nam SW Rhee H Koh KH Kim H 《Experimental and molecular pathology》2011,(2):201-209
A subset of gastric carcinomas shows histologic evidence of a multistep process, progressing from gastric adenoma to gastric carcinoma. We examined gene expression changes during the gastric adenoma-carcinoma sequence in 26 snap-frozen samples (normal mucosa, adenoma, and carcinoma samples from eight patients and two additional carcinomas) by oligonucleotide microarray. Unsupervised hierarchical clustering analysis demonstrated differential gene expression between gastric normal mucosa, adenomas and carcinomas.We identified 319 and 422 genes differentially regulated in adenoma and carcinoma, respectively, relative to normal mucosa, using a combination of Welch's t-test and fold-change analysis. Applying a combination of robust multi-category support vector machines to the data, reveal that 39 and 21 genes were gradually up- and down-regulated, respectively, in succession in normal mucosa, adenoma, and carcinoma samples. We validated gene expression levels of four genes: hydroxyprostaglandin dehydrogenase 15 (HPGD), follistatin-like 1, trefoil factor 1 (TTF1) and trefoil factor 2 (TFF2) by RT-PCR and found direct correlation with microarray results. The expressions of the TFF2 and HPGD genes were further evaluated by immunohistochemistry in 103 adenomas and 70 carcinomas; expression of both proteins was decreased in these tissues. The progressive alteration in gene expression in the transition from normal mucosa to carcinoma suggests that these changes may play critical roles in gastric carcinogenesis. 相似文献
20.
Compérat E Camparo P Haus R Chartier-Kastler E Radenen B Richard F Capron F Paradis V 《Virchows Archiv : an international journal of pathology》2007,450(4):419-424
Aurora-A, a member of serine/threonine kinase, is implied in mitosis and centrosome maturation. Increasing levels of Aurora-A
have been shown to be present in several malignancies and especially in bladder cancer. No immunohistochemical marker has
shown to be able to predict the clinical outcome of patients with superficial bladder cancer, except MIB-1, as a predictive
marker of relapse and progression. The aim was to investigate the expression of Aurora-A and MIB-1 in tissue micro arrays
of superficial bladder cancer representative of pTa papillary urothelial neoplasm with different degrees of aggressiveness
(low malignant potential [PUNLMP], non-invasive papillary urothelial carcinoma low grade [NILGC], non-invasive papillary urothelial
carcinoma high grade [NIHGC] and carcinoma in situ). We analysed predictive values of both markers, their specificity and
sensitivity in tumor recurrence. Aurora-A was a sensitive marker to predict tumor recurrence especially for pTa (PUNLMP, NILGC;
PUNLMP p < 0.001, NILGC p < 0.001) with statistical significant correlation between immunohistochemical staining and clinical outcome. MIB-1 expression
displayed statistical difference p = 0.002 in the PUNLMP group and p = 0.03 in the NILGC group. Aurora-A is a more sensitive marker than MIB-1 to predict relapse in pTa bladder neoplasias. The
combination of both markers seems to have a very powerful predictive value of recurrence (p < 0.001). 相似文献