Asparaginase-like protein 1 expression in curettage independently predicts lymph node metastasis in endometrial carcinoma: a multicentre study.

OBJECTIVE: Correct preoperative identification of high-risk patients is important to optimise surgical treatment and improve survival. We wanted to explore if asparaginase-like protein 1 (ASRGL1) expression in curettage could predict lymph node metastases and poor outcome, potentially improving preoperative risk stratification. DESIGN: Multicentre study. SETTING: Ten hospitals in Norway, Sweden and Belgium. POPULATION: Women diagnosed with endometrial carcinoma. METHODS: ASRGL1 expression in curettage specimens from 1144 women was determined by immunohistochemistry. MAIN OUTCOME MEASURES: ASRGL1 status related to disease-specific survival, lymph node status, preoperative imaging parameters and clinicopathological data. RESULTS: ASRGL1 expression had independent prognostic value in multivariate survival analyses, both in the whole patient population (hazard ratio (HR) 1.63, 95% CI 1.11-2.37, P = 0.012) and in the low-risk curettage histology subgroup (HR 2.54, 95% CI 1.44-4.47, P = 0.001). Lymph node metastases were more frequent in women with low expression of ASRGL1 compared with women with high ASRGL1 levels (23% versus 10%, P < 0.001), and low ASRGL1 level was found to independently predict lymph node metastases (odds ratio 2.07, 95% CI 1.27-3.38, P = 0.003). CONCLUSIONS: Low expression of ASRGL1 in curettage independently predicts lymph node metastases and poor disease-specific survival. TWEETABLE ABSTRACT: Low ASRGL1 expression in curettage predicts lymph node metastasis and poor survival in endometrial carcinoma.

Placental inflammation in pre-eclampsia by Nod-like receptor protein (NLRP)3 inflammasome activation in trophoblasts.

Pre-eclampsia is associated with increased levels of cholesterol and uric acid and an inflamed placenta expressing danger-sensing pattern recognition receptors (PRRs). Crystalline cholesterol and uric acid activate the PRR Nod-like receptor protein (NLRP)3 inflammasome to release interleukin (IL)-1ß and result in vigorous inflammation. We aimed to characterize crystal-induced NLRP3 activation in placental inflammation and examine its role in pre-eclampsia. We confirmed that serum total cholesterol and uric acid were elevated in pre-eclamptic compared to healthy pregnancies and correlated positively to high sensitivity C-reactive protein (hsCRP) and the pre-eclampsia marker soluble fms-like tyrosine kinase-1 (sFlt-1). The NLRP3 inflammasome pathway components (NLRP3, caspase-1, IL-1ß) and priming factors [complement component 5a (C5a) and terminal complement complex (TCC)] were co-expressed by the syncytiotrophoblast layer which covers the placental surface and interacts with maternal blood. The expression of IL-1ß and TCC was increased significantly and C5a-positive regions in the syncytiotrophoblast layer appeared more frequent in pre-eclamptic compared to normal pregnancies. In-vitro activation of placental explants and trophoblasts confirmed NLRP3 inflammasome pathway functionality by complement-primed crystal-induced release of IL-1ß. This study confirms crystal-induced NLRP3 inflammasome activation located at the syncytiotrophoblast layer as a mechanism of placental inflammation and suggests contribution of enhanced NLRP3 activation to the harmful placental inflammation in pre-eclampsia.

Tumour apparent diffusion coefficient is associated with depth of myometrial invasion and is negatively correlated to tumour volume in endometrial carcinomas.

AIM: To explore possible correlations between tumour apparent diffusion coefficient (ADC), morphological tumour volume, and clinical and histological characteristics in endometrial carcinomas and to evaluate interobserver agreement for preoperative staging by MRI and for ADC measurements. MATERIALS AND METHODS: Preoperative conventional MRI including diffusion-weighted imaging (DWI) was performed in 105 endometrial carcinoma patients. Three radiologists independently reviewed the images for the presence of deep myometrial invasion, cervical stromal invasion, and lymph node metastases, and measured tumour ADC in regions of interest (ROIs). ADC values were analysed in relation to histomorphological characteristics and tumour volume. Kappa coefficients (κ) and intraclass correlation coefficients (ICC) for interobserver agreement for MRI staging results and ADC measurements, respectively, were calculated, and receiver operating characteristic (ROC) curves for identification of deep of myometrial invasion were generated. RESULTS: Mean tumour ADC was significantly lower in tumours with deep myometrial invasion (ADC = 0.75 × 10(-3) mm(2)/s) compared to tumours with superficial or no myometrial invasion (ADC = 0.85 × 10(-3) mm(2)/s; p < 0.001). ADC was negatively correlated to tumour size (p = 0.007). The interobserver agreement was fair (κ = 0.32) for depth of myometrial invasion, good for cervical stromal invasion (κ = 0.66), and moderate for lymph node metastases (κ = 0.54), and the interobserver variability for ADC value measurements was low (ICC = 0.60). CONCLUSION: Tumour ADC measurements may in the future provide an adjunct tool, aiding in the preoperative identification of high-risk patients with deep myometrial infiltration.

Increased microvascular proliferation is negatively correlated to tumour blood flow and is associated with unfavourable outcome in endometrial carcinomas.

BACKGROUND: We aimed to study the angiogenic profile based on histomorphological markers in endometrial carcinomas in relation to imaging parameters obtained from preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) and to explore the potential value of these markers to identify patients with poor outcome. METHODS: In fifty-four surgically staged endometrial carcinoma patients, immunohistochemical staining with factor VIII and Ki67 allowed assessment of microvessel density (MVD) and microvascular proliferation reflecting tumour angiogenesis. In the same patients, preoperative pelvic DCE-MRI and DWI allowed the calculation of parameters describing tumour microvasculature and microstructure in vivo. RESULTS: Microvascular proliferation was negatively correlated to tumour blood flow (Fb) (r=-0.36, P=0.008), capillary permeability surface area product (PS) (r=-0.39, P=0.004) and transfer from the blood to extravascular extracellular space (EES) (Ktrans) (r=-0.40, P=0.003), and was positively correlated to tumour volume (r=0.34; P=0.004). High-tumour microvascular proliferation, low Fb and low Ktrans were all significantly associated with reduced progression/recurrence-free survival (P<0.05). CONCLUSION: Disorganised angiogenesis with coexisting microvascular proliferation and low tumour blood flow is a poor prognostic factor supporting that hypoxia is associated with progression and metastatic spread in endometrial carcinomas.

Increased endoplasmic reticulum stress in decidual tissue from pregnancies complicated by fetal growth restriction with and without pre-eclampsia.

OBJECTIVES: Endoplasmic reticulum (ER) stress has been implicated in both pre-eclampsia (PE) and fetal growth restriction (FGR), and is characterised by activation of three signalling branches: 1) PERK-pEIF2α, 2) ATF6 and 3) splicing of XBP1(U) into XBP1(S). To evaluate the contribution of ER stress in the pathogenesis of PE relative to FGR, we compared levels of ER stress markers in decidual tissue from pregnancies complicated by PE and/or FGR. STUDY DESIGN: Whole-genome transcriptional profiling was performed on decidual tissue from women with PE (n = 13), FGR (n = 9), PE+FGR (n = 24) and controls (n = 58), and used for pathway and targeted transcriptional analyses of ER stress markers. The expression and cellular localisation of ER stress markers was assesses by Western blot and immunofluorescence analyses. RESULTS: Increased ER stress was observed in FGR and PE+FGR, including both the PERK-pEIF2α and ATF6 signalling branches, whereas ER stress was less evident in isolated PE. However, these cases demonstrated elevated levels of XBP1(U) protein. ATF6 and XBP1 immunoreactivity was detected in most (>80%) extravillous trophoblasts, decidual cells and macrophages. No difference in the proportion of immunopositive cells or staining pattern was observed between study groups. CONCLUSIONS: Increased PERK-pEIF2α and ATF6 signalling have been associated with decreased cellular proliferation and may contribute to the impaired placental growth characterising pregnancies with FGR and PE+FGR. XBP1(U) has been proposed as a negative regulator of ER stress, and increased levels in PE may reflect a protective mechanism against the detrimental effects of ER stress.

STOX2 but not STOX1 is differentially expressed in decidua from pre-eclamptic women: data from the Second Nord-Trondelag Health Study.

Variation in the Storkhead box-1 (STOX1) gene has previously been associated with pre-eclampsia. In this study, we assess candidate single nucleotide polymorphisms (SNPs) in STOX1 in an independent population cohort of pre-eclamptic (n = 1.139) and non-pre-eclamptic (n = 2.269) women (the HUNT2 study). We also compare gene expression levels of STOX1 and its paralogue, Storkhead box-2 (STOX2) in decidual tissue from pregnancies complicated by pre-eclampsia and/or fetal growth restriction (FGR) (n = 40) to expression levels in decidual tissue from uncomplicated pregnancies (n = 59). We cannot confirm association of the candidate SNPs to pre-eclampsia (P > 0.05). For STOX1, no differential gene expression was observed in any of the case groups, whereas STOX2 showed significantly lower expression in deciduas from pregnancies complicated by both pre-eclampsia and FGR as compared with controls (P = 0.01). We further report a strong correlation between transcriptional alterations reported previously in choriocarcinoma cells over expressing STOX1A and alterations observed in decidual tissue of pre-eclamptic women with FGR.

Matrix metalloproteinase 1 in pre-eclampsia and fetal growth restriction: reduced gene expression in decidual tissue and protein expression in extravillous trophoblasts.

Superficial invasion of extravillous trophoblasts (EVTs) and impaired spiral artery remodelling are characterizing phenomena in pregnancies complicated by pre-eclampsia (PE) and fetal growth restriction (FGR). However, the underlying causes remain unclear. In this study, gene expression in decidua basalis tissue from pregnancies complicated with PE and/or FGR (n = 18) and normal pregnancies (n = 17) was assessed by Affymetrix HG Focus microarray to obtain hints of mechanisms involved in the pathogenesis. A total of 200 differentially expressed transcripts were detected at a false discovery rate (FDR)

Medical abortion at 63 to 90 days of gestation.

OBJECTIVE: To evaluate medical abortion as a treatment alternative for late first-trimester abortions and to evaluate the decrease in beta-hCG after abortion at 63-90 days of gestation. METHODS: All women received mifepristone 200 mg orally, followed by 800 micrograms misoprostol vaginally 48 hours later. Misoprostol was repeated every 3 hours orally, to a maximum of five doses if needed. A clinical examination including ultrasonography was performed 8-14 days after treatment. beta-hCG level was determined before treatment and at follow-up. RESULTS: A total of 254 pregnant women with gestational age 63 to 90 days were included. The successful termination rate was 91.7%. Surgical evacuation was carried out in 21 (8.3%) women. Most women (91.0%) found the method of treatment highly acceptable. The beta-hCG levels of women with successful termination had decreased more than 97.5% at follow-up. CONCLUSION: Medical abortion is an effective and acceptable method for termination of pregnancy in late first trimester.

Placental expression of glycophosphatidylinositol (GPI)-anchored proteins in paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) is a clonal stem cell disorder in which a defect of glycophosphatidylinositol (GPI)-anchored proteins leads to higher morbidity and mortality because of intravascular haemolysis, haemoglobinuria, pancytopenia and an increased frequency of thrombotic events. We report here the clinical features of a pregnant woman with PNH and present an immunhistochemical analysis of complement regulators, leukocyte activation markers and placental alkaline phosphatase (PALP) on syncytiotrophoblasts and inflammatory cells in her placenta. Placental tissue from normal deliveries served as controls. The patient had severe PNH with haemolysis, thrombosis episodes and signs of bone marrow failure. Placental syncytiotrophoblasts and villous cells of fetal origin in both normal placentas and the placenta from the PNH patient expressed PALP and the complement regulators CD46, CD55 and CD59. Additionally, CD11b-positive leukocytes of presumed maternal origin were negative for CD15 in the PNH placenta, while they stained positive within the villous space and in normal placentas. These findings show that fetally derived cells in the PNH placenta expressed GPI-linked molecules that are known to be of importance for a successful pregnancy outcome.

Minimal residual disease in ovarian cancer as a target for complement-mediated mAb immunotherapy.

Ovarian cancer is potentially well suited for local monoclonal antibody (mAb) immunotherapy, because it remains within the peritoneal cavity for a long period of time before giving rise to distant metastases. At the stage of minimal residual disease, the cells appear to be in a state of dormancy (G(0)) or at least have lower rates of tumour cell proliferation. They should be a promising target for immunotherapy. Here we first examined the cell-cycle expression of CD59 and decay-accelerating factor (DAF; CD55) on four different ovarian carcinoma cell lines, using simultaneous flow cytometric analysis of DNA content or the cell-cycle-specific nuclear proliferation protein Ki67 and CD59 or DAF surface expression. We found that CD59 and DAF are stably expressed throughout the cell cycle. The polyvalent approach to target-independent antigens to improve the efficiency of mAb complement (C)-mediated damages was promising, and tumour cells become sensitive to C damage, when incubated with cross-linked mAb against different tumour-associated antigens. Although, such immune complex-mediated C activation was rather ineffective in killing the cells, it could be potentiated by the addition of blocking mAb against CD59 and DAF. Our results suggest that the activities of intrinsic C regulators must be neutralized to make minimal residual disease a promising target for antibody therapy.

Cardiopulmonary distress during obstetrical anaesthesia: attempts to diagnose amniotic fluid embolism in a case series of suspected allergic anaphylaxis.

BACKGROUND: Cardiopulmonary distress during obstetrical anaesthesia may result from a drug-induced allergic reaction, but, in the obstetrical setting, allergic anaphylaxis may be inseparable from amniotic fluid embolism in terms of the clinical presentation. Further investigations, using allergy tests and other laboratory analyses, are then needed to pursue a diagnostic clarification. METHODS: Twelve women suspected of having developed anaphylaxis during obstetrical anaesthesia underwent allergy follow-up investigations and further serological tests with the amniotic fluid embolism marker sialyl Tn and complement factors (C3 and C4) in an attempt to differentiate amniotic fluid embolism from drug-induced allergic anaphylaxis. RESULTS: The diagnostic programme revealed one case of probable amniotic fluid embolism and four cases of probable drug-induced allergic anaphylaxis. Of the remaining seven cases, there were two cases that, by diagnostic exclusion, could be classified as possible cases of amniotic fluid embolism. The cause of the reactions remained unresolved in five cases. CONCLUSIONS: It can be difficult to differentiate between anaphylaxis and amniotic fluid embolism, especially amongst survivors. Diagnostic markers that can be applied on peripheral blood samples are promising, but larger studies are needed to validate their use in the diagnosis of causes of cardiopulmonary distress during obstetrical anaesthesia.

Ascitic complement system in ovarian cancer.

Ovarian cancer spreads intraperitoneally and forms fluid, whereby the diagnosis and therapy often become delayed. As the complement (C) system may provide a cytotoxic effector arm for both immunological surveillance and mAb-therapy, we have characterised the C system in the intraperitoneal ascitic fluid (AF) from ovarian cancer patients. Most of the AF samples showed alternative and classical pathway haemolytic activity. The levels of C3 and C4 were similar to or in the lower normal range when compared to values in normal sera, respectively. However, elevated levels of C3a and soluble C5b-9 suggested C activation in vivo. Malignant cells isolated from the AF samples had surface deposits of C1q and C3 activation products, but not of C5b-9 (the membrane attack complex; MAC). Activation could have become initiated by anti-tumour cell antibodies that were detected in the AFs and/or by changes on tumour cell surfaces. The lack of MAC was probably due to the expression of C membrane regulators CD46, CD55 and CD59 on the tumour cells. Soluble forms of C1 inhibitor, CD59 and CD46, and the alternative pathway inhibitors factor H and FHL-1 were present in the AF at concentrations higher than in serum samples. Despite the presence of soluble C inhibitors it was possible to use AF as a C source in antibody-initiated killing of ovarian carcinoma cells. These results demonstrate that although the ovarian ascitic C system fails as an effective immunological surveillance mechanism, it could be utilised as an effector mechanism in therapy with intraperitoneally administrated mAbs, especially if the intrinsic C regulators are neutralised.

Secretion of soluble complement inhibitors factor H and factor H-like protein (FHL-1) by ovarian tumour cells.

We observed that the soluble complement regulators factor H and factor H-like protein were abundantly present in ascites samples as well as in primary tumours of patients with ovarian cancer. RT-PCR and immunoblotting analyses showed that the two complement inhibitors were constitutively produced by the ovarian tumour cell lines SK-OV-3 and Caov-3, but not PA-1 or SW626 cells. The amounts of factor H-like protein secreted were equal to those of factor H. This is exceptional, because e.g. in normal human serum the concentration of factor H-like protein is below 1/10th of that of factor H. In ascites samples the mean level of factor H-like protein (130+/-55 microg ml(-1)) was 5.5-fold higher than in normal human serum (24+/-3 microg ml(-1)). Ovarian tumour cells thus preferentially synthesise factor H-like protein, the alternatively spliced short variant of factor H. The tumour cells were found to bind both (125)I-labelled factor H and recombinant factor H-like protein to their surfaces. Surprisingly, the culture supernatants of all of the ovarian tumour cell lines studied, including those of PA-1 and SW626 that did not produce factor H/factor H-like protein, promoted factor I-mediated cleavage of C3b to inactive iC3b. Subsequently, the PA-1 and SW626 cell lines were found to secrete a soluble form of the membrane cofactor protein (CD46). Thus, our studies reveal two novel complement resistance mechanisms of ovarian tumour cells: (i) production of factor H-like protein and factor H and (ii) secretion of soluble membrane cofactor protein. Secretion of soluble complement inhibitors could protect ovarian tumour cells against humoral immune attack and pose an obstacle for therapy with monoclonal antibodies.

Early pregnancy termination with mifepristone and misoprostol in Norway.

OBJECTIVES: Medical abortion was first introduced in Norway in April 1998. The aims of this study were to assess the efficacy, side effects, and acceptability of medical abortion using mifepristone orally and misoprostol vaginally in a Norwegian population. DESIGN: The study included the first 226 pregnant women with gestational age of <63 days who requested nonsurgical abortion during the first year in the first Norwegian hospital using this regimen. METHODS: All women received a single dose of mifepristone 600 mg orally, followed at 48 hours by 800 microg misoprostol vaginally. Treatment outcome and complications were the principal outcome measures. We also measured the rates of side effects such as abdominal pain and bleeding and the women's acceptability of treatment. RESULTS: Abortion was successful in 95%, surgical evacuation became necessary in 4%, and the pregnancy continued in one woman. During the study period the method was chosen by 23% of those requesting abortion before 63 days amenorrhea; 80% would use the method again; 81% would recommend it to a friend; in retrospect, 69% would not have been willing to be randomly allocated to either a medical or a surgical method. CONCLUSIONS: The combination of orally administrated mifepristone and vaginally administrated misoprostol is an abortion method that is both effective and safe, has few side effects and is well accepted by Norwegian women.

[Mifepristone--a controversial drug with great potential]. / Mifepriston--et kontroversielt legemiddel med stort potensial.

BACKGROUND: Antiprogestins, agents that inhibit the action of progesterone, are among the most controversial and yet the more interesting therapeutic compounds developed over the past 20 years. MATERIAL AND METHODS: We present a review of the literature identified through limited searches on Medline, Cochrane and the Internet, with a discussion of the biological, clinical, political and ethical aspects of this important drug. RESULTS: The first effective antiprogestin in clinical use was mifepristone (also known as RU 486). This agent provides the most effective and safest means of medical abortion. It may also be used as a contraceptive and delivery-inducing agent and in the treatment of spontaneous abortion, ectopic pregnancies, leiomyoma, endometriosis, intrauterine fetal death, Cushing's syndrome and progesterone-dependent malignancies. INTERPRETATION: The introduction of mifepristone as an abortion-inducing agent has created intense political, ethical and moral controversies which have delayed clinical investigations and evaluations for potential expanded use.

[HELLP syndrome]. / HELLP-syndromet.

BACKGROUND: The HELLP syndrome (H = hemolysis, EL = elevated liver enzymes, LP = low platelets) is a pregnancy complication which affects 10-20% of cases of severe preeclampsia. MATERIAL AND METHODS: The article is a review of the literature. RESULTS: Approximately 70% of HELLP syndrome cases occur before delivery, 15% as early as in the second trimester, the remainder after delivery. The classical HELLP syndrome is characterised by abdominal pain, pathological liver tests and low platelets. However, some cases are atypical; hypertension and abdominal pain may both be absent. Genetic as well as immunologic factors are involved in the pathogenesis. There is an imbalance in the coagulation process in the placenta. Activated leukocytes and macrophages induce production of cytokines that may reach the general circulation and cause endothelial dysfunction. In the HELLP syndrome fibrin deposits are also found in the vessels and in the liver sinusoides. INTERPRETATION: A mother with a classic HELLP syndrome should be delivered after stabilisation of the clinical condition. A partial HELLP syndrome can be observed. Treatment with corticosteroids is beneficial.

[Pathophysiology and clinical manifestations in pre-eclampsia]. / Patofysiologi og kliniske manifestasjoner ved preeklampsi.

BACKGROUND: Preeclampsia is a progressive, multisystem disorder characterised by hypertension and proteinuria. A body of evidence suggest a genetic basis; it is generally accepted that the underlying pathological processes are in the placenta. MATERIAL AND METHODS: This article is a review of the pathophysiology of preeclampsia based on literature mainly obtained through PubMed and Medline searches. RESULTS: A poorly perfused placenta, secondary to defective placental invasion of the spiral arteries, may lead to hypoxia and insufficient perfusion and cause release of cytokines which damage endothelial cells and cause dysfunction. Women with preeclampsia have markedly elevated concentrations of triglyceride-rich lipoproteins. Lipid peroxidation also causes endothelial dysfunction and thus contributes to preeclampsia. Placenta is one source of the lipid peroxides. Antioxidant deficiency is also a predisposing factor. Hyperhomocysteinaemia, protein S and protein C deficiency, and activated protein C resistance appear to be involved in the pathophysiology of severe preeclampsia and early onset preeclampsia. INTERPRETATION: The new information about mechanisms for development of preeclampsia gives a basis for new treatment modalities.

[Pre-eclampsia--a review]. / Preeklampsi--en oversikt.

BACKGROUND: Preeclampsia is characterized by hypertension and proteinuria with or without oedema. MATERIAL AND METHODS: The authors highlight some aspects of preeclampsia: epidemiology, classification, clinical evaluation and treatment. RESULTS: The condition may be classified as light or severe. Preeclampsia can induce damage to the placenta, liver, kidneys and brain, in addition to complications like the HELLP syndrome, placental abruption and eclampsia. Thrombocyte activation may cause activation of the coagulation system and thrombocytopenia. Early onset preeclampsia (< 34 weeks) is often associated with placental infarcts and reduced fetal growth. INTERPRETATION: We focus on early signs and close clinical surveillance. The diastolic blood pressure should be estimated with Korotkoffs' phase V. Patients with early onset preeclampsia should be hospitalized, as should women with hypertension and newly developed proteinuria. Antihypertensive treatment is discussed. Cases with reduced fetal growth and those with severe preeclampsia should in most cases be delivered preterm. Vaginal delivery is preferable. Labour may be induced by oxtocin, following cervical prostaglandin stimulation as indicated. In such cases cardiotocography surveillance during labour should be performed. Caesarean section may be performed in selected cases. Patients with mild preeclampsia can await spontaneous vaginal delivery at term, but delivery should be induced if they proceed past term.

[The complement system--structure, activation, regulation and function]. / Komplementsystemet--oppbygning, aktivering, regulering og funksjon.

Activation of the complement system plays a key role in normal inflammatory response to injury but may cause substantial injury when activated inappropriately. The cascade is activated through classical, alternative and lectin pathways. The human complement system is in most cases well controlled by the host, and inappropriate activation and host cell destruction are prevented. The control is mainly mediated by complement regulatory proteins. The use of powerful methodologies in molecular biology, biochemistry and physiology has led to impressive advances in our knowledge of the mechanisms of complement activation and regulation and its role as either a protective or pathogenic factor in human disease. With respect to disease pathogenesis, the complexity of the cascades provides opportunities for several different therapeutic targets within the pathways, and we are about to witness the availability of a variety of complement modulators for specific therapies. This article reviews biological aspects of this important immunological effector mechanism.

Decreased expression of protectin (CD59) in gut epithelium in ulcerative colitis and Crohn's disease.

Without adequate protection, the cells of the human body would be susceptible to destruction by the complement system. The main defense against complement lysis is a molecule called protectin (CD59) that is widely distributed in human tissues. Because the complement system has been suggested to be involved in the pathogenesis of inflammatory bowel diseases, we examined the expression of protectin in the colonic epithelium of patients with ulcerative colitis or Crohn's disease and controls. Colorectal specimens from 6 patients with ulcerative colitis, 8 patients with Crohn's disease, and 4 controls were obtained from surgical resections. Frozen sections of the specimens were immunostained for protectin using the Bric 229 monoclonal antibody. The expression of protectin was found to be decreased in the epithelium of patients with ulcerative colitis. In patients with Crohn's disease, the epithelial expression of protectin was decreased in diseased areas of gut while the expression did not significantly differ from that in controls in macroscopically normal areas. There was no difference in the expression of protectin on vascular endothelium, mononuclear cells, or smooth muscle. The reduction in epithelial expression of protectin in patients with ulcerative colitis or Crohn's disease may render epithelial cells vulnerable to complement lysis and lead to the destruction of gut epithelium as seen typically in these diseases.