Faecal calprotectin is elevated in patients with gastric cancer

Faecal calprotectin is elevated in patients with gastric cancer

April 1995 Gastrointestinal Oncology A493 • DECREASED E-CADHERIN EXPRESSION IS A S S O C I A T E D W I T H P O O R P R O G N O S I S IN P A T I E N ...

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April 1995

Gastrointestinal Oncology A493

• DECREASED E-CADHERIN EXPRESSION IS A S S O C I A T E D W I T H P O O R P R O G N O S I S IN P A T I E N T S W I T H B A R R E T T ' S ADENOCARCINOMAS. K.K.Krishnadath, H.W. Tilanus, M. van B l a n k e n s t e i n and F.T. Bosman. The e s o p h a g e a l tumour study group, Erasmus University Rotterdam, The Netherlands.

FAECAL CALPROTECTIN IS E L E V A T E D IN PATIENTS WITH GASTRIC CANCER. J.Kristinsson,A.G.Reseth*, K.Nygaard, E.Aadland*,M.K.Fagerhol** and H.Schjensby*Dept. of Surgery and Medicine*, Aker University Hospital, Blood Bank and Dept. of Immunology, Ullevaal University Hospital**, Oslo,Norway.

D e c r e a s e d levels of the c e l l - c e l l a d h e s i o n m o l e c u l e E - C a d h e r i n are a s s o c i a t e d w i t h loss of d i f f e r e n t i a t i o n in a n u m b e r of carcinomas. H o w ever, the v a l u e of E - C a d h e r i n as a p r o g n o s t i c m a r k e r in these cancers is largely undetermined. To d e t e r m i n e the prognostic significance of aberrant E-Cadherin expression in Barrett's a d e n o c a r c i n o m a s specimens were evaluated immuno h i s t o c h e m i c a l l y for E - C a d h e r i n e x p r e s s i o n and the r e s u l t s w e r e r e l a t e d to h i s t o l o g i c a l grade, t u m o r stage, p r e s e n c e of m e t a s t a s i s and survival. I m m u n o h i s t o c h e m i s t r y w i t h an E - C a d h e r i n s p e c i f i c monoclonal antibody (5H9) was applied to archival t i s s u e sections. E - C a d h e r i n e x p r e s s i o n was scored in 84 d i f f e r e n t t u m o r areas w i t h v a r y i n g d e g r e e s of d i f f e r e n t i a t i o n (GI-G3) of 39 esophageal resection specimens containing B a r r e t t ' s adenocarcinomas. T h r e e m a i n p a t t e r n s were found: normal E - C a d h e r i n e x p r e s s i o n (<10% n e g a t i v e cells), h e t e r o g e n o u s e x p r e s s i o n (i0 to 90% n e g a t i v e cells) and t u m o r areas w i t h o u t ECadherin expression (>90% n e g a t i v e cells). A s i g n i f i c a n t c o r r e l a t i o n was found b e t w e e n loss of E-cadherin expression and tumor grade (Spearman R a n k corr coef 0.85, p<0.001). A l s o s i g n i f i c a n t c o r r e l a t i o n s w e r e found b e t w e e n Ec a d h e r i n e x p r e s s i o n a n d m e t a s t a s i s (Fisher exact test p<0.001) and survival (Logrank test, p < 0 , 0 5 ) . T h e s e r e s u l t s suggest that E - C a d h e r i n can serve as a prognostic factor for the surv i v a l of p a t i e n t s w i t h B a r r e t t ' s adenocarcin0mas.

Our group has earlier shown that faecal excretion of calprotectin, a calcium binding neutrofil leukocyte protein is elevated in most

• Chronological Sequence Of Dextran Sulfate Sodium Induced Acute And Chronic Colitis Associated With Dysplasia In The Rat. F. Knllmann V. Gross, M. Alt, H. Messmanm J. Scbolmerieh, J. Riischoff*. Depts. of Internal Medicine I and *Pathology, University of Regensburg, 93042 Regensburg, Germany. Background: A reliable ammal model for the production of premnlignant colonic lesions which occur during the development of colonic cancer in chronic ulcerative colitis is needed. A small number of experiments mentioned the carcinogenic effects of dexttan sulfate sodium (DSS) in the large bowel of mice, rats, rabbits and Syrian hamsters. Until now a precise analysis of the chronological sequence acute-chrome colitis with or without dysplasia is lacking for the DSS colitis in rats. Methods: Male Wistar rats. weighing 90120g were used for the experiments. The rats received 5% (Wt/vol) DSS (mol wt 54000) in their drinking water. Eight experimental groups were formed: AI=four days DSS, All=seven days DSS. BI=seven days DSS followed by ten days water (= one cycle) BII=t-wo cycles ... BVl=six cycles). Colonic injury was determined maeroseopieally and histologically. Dysplasia was graded according to Riddell et al (1984) (Dl=indefiaite probably negative for dysplasia, D2=indefinite probably positive for dysplasia. D3=hiw-grade dysplasia, D4=high-grade dysplnsia). Results: In group AI we found colonic ulcers in 15 of 16 rats predommately on the left side of the colon (13/15). D1 lesions were observed in eight rats. In group All all rats (n=6) showed colonic ulcerations. 2 of 6 rats had a total severe colitis. In group All only regenerative epithelial lesions (DI) v,ere seen (n=2). All rats of group BI (n=7) showed colitis with the following incidence of dysplastic lesions: 6/7 DI, 5/7 D2, 2/7 D3. Epithelial dysplastic lesions were dispersed throughout the whole colon. In groups BII to BIV no dysplasia was observed. After five or six cycles of DSS (groups BV and BVI) all"rats (n=6) showed dysplasuc lesions at multiple sites ranging from DI to D3. High-grade dysplasia was not detected. Conclusion: After seven days of DSS treatment followed by ten days water (BI) 70% of rats showed epithelial lesions probably positive for dysplasia and 28% low-grade dysplasia. Dysplastic lesions at multiple sites and different degrees occurred after five cycles DSS (BV). For the development of high-grade dysplasia or colorectnl cancer presumably more cycles or longer time intervals are needed. The DSS colitis model in the rat appears suited to study the relation between colonic inflammation and the development of epithelial dysplnsia.

p a t i e n t s w i t h c o l o r e c t a l c a n c e r and a c t i v e i n f l a m m a t o r y b o w e l diseases. In a series of non selected, n e w l y d i a g n o s e d patients with gastric cancer, faecal calprotectin was raised above the upper reference value o f 10 mg/l in 20 of 20 patients (range 13-230 mgfl, median 56 rag/l). In patients operated on (11 patients) p T p N p M classification s h o w e d 2 patients w i t h p T l , p N 0 , M x , 2 patients w i t h pT2, p N 0 - l , M x and 7 patients with pT3,pN 1-2,Mx. In this preliminary material m e d i a n faecal calprotectin in patients with adenocarcinoma pT1 and pT2 stages was 40 mg/l as c o m p a r e d to 59 m g / l in patients with pT3 adenocarcinoma(n.s.). In one patient w i t h e l e v a t e d c a l p r o t e c t i n ( 1 4 0 m g / l ) and a n o r m a l e n d o s c o p y , b i o p s i e s s h o w e d chronic gastritis. U l t r a s o n o g r a p h y and repeated g a s t r o s e o p y with d e e p e r b i o p s i e s s h o w e d linitis plastica w i t h o u t infiltration of the gastric mucosa. W h e t h e r patients i n f e c t e d w i t h H e l i c o b a c t e r p y l o r y (Hp) h a v e e l e v a t e d calprotectin excretion is not k n o w n , h o w e v e r in a series o f 144 patients ( m e a n age 62 y e a r s ) the great majority had n o r m a l c a l p r o t e c t i n levels. Since more t h a n 5 0 % of these p e r s o n s are probably Hp+ it is unlikely that Hp infection per se leads to increased faecal calprotectin level, Calprotectin can be accurately assessed in small stool samples and is r e m a r k a b l y resistant to degradation in the presence of calcium. In c o m p a r i s o n h a e m o g l o b i n is more readily degraded, and has therefore p r o b a b l y l o w e r s e n s i t i v i t y in d e t e c t i n g g a s t r i c c a n c e r t h a n Calprotectin.

• Comparison Between Nuclenlar Organizer Region Staining And MIB-I Staining In Dysplasia in Inflammatory bowel disease (IBD). F. Kullmann, MR. Fadaie*. V. Gross, J. Schrlmerich, J.Rt~schoff*, Depts. of Internal Medicine I and *Pathology, University.of Regensburg, 93042 Regensburg: Germany Background: Quantitation of nucleolar organizer regions visualised by silver staining (AgNORs) has attracted interest as a means of grading in human malignancies. In the present study, we compared AgNOR staining which demonstrates rDNA loops transcribing for ribosomes with MIB-1 an antibody against recombinant parts of the Ki-67 proliferating associated antigen for detecting dysplasia in IBD. Methods: A total of 69 paraffin-embedded eolorectal biopsies were obtained from 40 patients (30 = 1BD. 10 = Normal). Dysplasias (DI= indefinite probably positive for dysplasia n=25: DII= low-grade dysplasia n=9. DIII= high-grade @splasia n=6) were found in 40 biopsies. The percentage of positively stained nuclei was determined according to intensity (unequivocal positive)and to distribution throughout the mucosa (cr)ptic epithelium of upper half and lower half of total mucosa). AgNORs were evaluated by digital image analysis determining mean total area of AgNORs per cell (MNORA). Results: The following percentage of MIB-I positive stained nuclei or mean total area of AgNORs were detected in normal tissue and dysplasia:

Upper

Normal Dysplnsia MIB-I MIB-I 19.1_+90% 303-9.3% ,o o

Normal Dysplasia MNORA MNORA 3.0_+0.81am2 3.8-+1.31am2 .o o

Lower 39.3-+10.4% 40.1_+10.8% 4.0+l.2um ~ 4.l-+l.4am2 Wilcoxon test: * o = p<0.05 Irrespectively of localization into the c~1~t, MIB-I was able to discriminate sigmfieantly bet~veen biopsies with DII and Dill (30.9_+9.6% vs. 54.8+6.5%. p<0.001). MNORA only differentiated DI from controls in the upper crypt half (MNORA: 2.9_+0.8 ~amz vs. 3.6-+1.0 p~mz (DI). p<0.05). Conclusion: We demonstrated that the total area of AgNORs per cell is sigmficantly greater in the upper c~,pt half of dysplastic lesions compared to normal colonic mucosa compared to dysplas'ac epithelium. In addition to the latter. MIB-I tmmunostaming revealed significantly higher numbers of positive stained nuclei in dysplasias of higher degrees. MIB-I is thus superior to AgNORs in detecting precancerous lesions in IBD.