Mucin gene expression in Barrett's oesophagus: an in situ hybridisation and immunohistochemical study

BACKGROUND AND AIMS: Mucin genes are expressed in a site specific manner throughout the gastrointestinal tract. Little is known about the expression pattern in the oesophagus. In this study we have investigated MUC gene expression in both the normal oesophagus and specialised intestinal metaplasia (Barrett's oesophagus). PATIENTS: Archived paraffin embedded material from eight specimens of normal oesophagus, 18 Barrett's oesophagus, eight gastric metaplasia, six high grade dysplasia, and six cases of adenocarcinoma were examined for expression of the mucin genes MUC1-6. METHODS: Mucin mRNA was detected by in situ hybridisation using [(35)S] dATP labelled oligonucleotide probes. Mucin core protein was detected by immunohistochemistry. RESULTS: Normal oesophagus expressed MUC5B in the submucosal glands and MUC1 and MUC4 in the stratified squamous epithelium. Barrett's oesophagus strongly expressed MUC5AC and MUC3 in the superficial columnar epithelium, MUC2 in the goblet cells, and MUC6 in the glands. In high grade dysplasia and adenocarcinoma there was downregulation of MUC2, MUC3, MUC5AC, and MUC6, but upregulation of MUC1 and MUC4 in half of the specimens examined. CONCLUSIONS: Normal oesophagus and Barrett's oesophagus have a novel pattern of mucin gene expression. Barrett's oesophagus expressed the mucins associated with normal gastric epithelium and normal intestinal epithelium. While most mucin genes were downregulated in severely dysplastic and neoplastic tissues, there was upregulation of the membrane bound mucins MUC1 and MUC4. This may prove useful in detecting early signs of progression to adenocarcinoma of the oesophagus.     

Coordinated localisation of mucins and trefoil peptides in the ulcer associated cell lineage and the gastrointestinal mucosa

BACKGROUND AND AIMS: Trefoil factor family (TFF) peptides and the chromosome 11p15.5 mucin glycoproteins are expressed and secreted in a site specific fashion along the length of the gastrointestinal tract. Evidence for coexpression of mucins and trefoil peptides has been suggested in numerous gastrointestinal mucosal pathologies. The ulcer associated cell lineage (UACL) occurs at sites of chronic ulceration in Crohn's disease, expresses all three trefoil peptides, and is implicated in mucosal restitution. We tested the hypothesis that individual trefoil peptides are uniquely localised with specific mucins in the UACL and normal gastrointestinal epithelia. METHODS: Expression of mucin genes in the UACL from small bowel tissue of patients with Crohn's disease was detected by in situ hybridisation, and localisation of the products by immunohistochemistry. Colocalisation of mucins and trefoil peptides was demonstrated by immunofluorescent colabelling in UACL and normal gastrointestinal epithelia. RESULTS: MUC5AC and TFF1 were colocalised in distal ductular and surface elements of the UACL and in foveolar cells of the stomach, whereas MUC6 and TFF2 were colocalised to acinar and proximal ductular structures in the UACL, in the fundus and deep antral glands of the stomach, and in Brunner's glands of the duodenum. MUC5B was found sporadically throughout the UACL and gastric body. MUC2 was absent from the UACL, Brunner's glands, and stomach. MUC2 and TFF3 were colocalised throughout the large and small bowel mucosa. CONCLUSIONS: The UACL has a unique profile of mucin gene expression. Coordinated localisation of trefoil peptides and mucins in UACL and normal gastrointestinal epithelia suggests they may assist each others' functions in protection and repair of gastrointestinal mucosa.     

The pathogenesis of duodenal gastric metaplasia: the role of local goblet cell transformation

BACKGROUND AND AIMS: Gastric metaplasia is frequently seen in biopsies of the duodenal cap, particularly when inflamed or ulcerated. In its initial manifestation small patches of gastric foveolar cells appear near the tip of a villus. These cells contain periodic acid-Schiff (PAS) positive neutral mucins in contrast with the alcian blue (AB) positive acidic mucins within duodenal goblet cells. Previous investigations have suggested that these PAS positive cells originate either in Brunner's gland ducts or at the base of duodenal crypts and migrate in distinct streams to the upper villus. To investigate the origin of gastric metaplasia in superficial patches, we used the PAS/AB stain to distinguish between neutral and acidic mucins and in addition specific antibodies to immunolocalise foveolar cell mucin MUC5AC, the foveolar cell secretory product, gastric trefoil factor (TFF1), the mature goblet cell mucin MUC2, and MUC2 core antigen. RESULTS: Cells in focal patches of gastric metaplasia contained secretory granules of both gastric and goblet cell phenotypes. MUC5AC and TFF1 were present as expected in gastric foveolar cells but in addition, MUC2 core antigen, normally present only in the Golgi of intestinal goblet cells, was expressed in secretory granules. Goblet cells in the vicinity of metaplastic patches also expressed both gastric and intestinal antigens. MUC5AC/MUC2 containing goblet cells were most common near the villus tip but were also seen at the base of crypts. Where crypts and Brunner's gland ducts merged they were always seen on the crypt side of the junction. Goblet cells were the only cells to express gastric antigens in these areas. In advanced metaplastic lesions, dual phenotype goblet cells were less evident and fewer cells expressed intestinal mucin antigens. CONCLUSIONS: We suggest that goblet cells that express both intestinal and gastric antigens may represent local precursors of gastric metaplasia undergoing a transition to foveolar-like cells of mixed phenotype at the site of early metaplastic patches. As metaplasia becomes more widespread, a more pure gastric phenotype emerges. This progression is likely to be controlled by local inflammatory signals.     

A confirmatory report for the close interaction of Helicobacter pylori with gastric epithelial MUC5AC expression

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with the development of gastritis and peptic ulcer and is presumed to be a risk factor for low-grade B-cell lymphoma and gastric cancer. H. pylori also causes critical alterations in gastric mucin structure. Our aim was to determine the effect of H. pylori on MUC1, MUC2, and MUC5AC expression. METHODS: Thirty H. pylori-positive and 15 H. pylori-negative antral gastric endoscopic biopsy specimens were evaluated for MUC1, MUC2, and MUC5AC expression with immunohistochemical staining. From the same specimens, we scrutinized the presence of H. pylori infection by hematoxylin and eosin and immunohistochemical staining. RESULTS: In H. pylori infected patients, the expression of MUC5AC was found to be localized to the cells in the superficial epithelium and upper parts of the gastric glands. The number of MUC5AC-expressing cells and the staining intensity of MUC5AC were shown to decrease in patients with H. pylori infection. Histopathology and immunostaining patterns of gastric mucins implied that H. pylori was physically associated with extracellular MUC5AC and MUC5AC-producing cells. H. pylori infection does not significantly affect staining intensity and patterns of MUC1 and MUC2 expressions. MUC1 was not found in dysplastic tissues or intestinal metaplasia areas. MUC5AC was expressed in dysplastic areas, but not in intestinal metaplasia. MUC2 was expressed in both dysplastic and intestinal metaplasia areas. CONCLUSION: H. pylori decreases the amount of MUC5AC expression. With reducing MUC5AC-producing cells and MUC5AC mucin, H. pylori may potentially cause significant alterations of the structure and function of gastric mucins. H. pylori-dependent inhibition of mucin synthesis deserves more investigations to clarify the role of H. pylori and gastric MUC5AC interaction.     

PDX1 homeobox protein expression in pseudopyloric glands and gastric carcinomas

BACKGROUND AND AIMS: Although it has been reported that intestinal metaplasia implicated in gastric carcinogenesis is induced by the ParaHox gene CDX2, it is unclear which genes are responsible for the formation of pseudopyloric glands and whether they play a role in gastric carcinogenesis. Pancreatic-duodenal homeobox 1 (PDX1) is also a ParaHox gene which contributes to the genesis and development of the pancreas, duodenum, and antrum. To clarify its significance for the formation of pseudopyloric glands and gastric carcinogenesis, we investigated expression of PDX1 and mucin in gastric carcinomas and surrounding mucosa. METHODS: Gastric carcinoma tissues from 95 patients were used for immunohistochemical analyses of PDX1, and mucins MUC6 and MUC5AC. RESULTS: PDX1 was found to be frequently expressed in pseudopyloric glands and intestinal metaplasia. MUC6 was more abundant than MUC5AC in pseudopyloric glands while higher levels of MUC5AC than MUC6 were evident in intestinal metaplasia. The frequency of PDX1 positive reactivity was higher in differentiated type carcinomas (39/43, 90.7%) and T1 carcinomas (42/43, 97.7%) than in undifferentiated type (33/52, 63.5%) and T2-4 (30/52, 57.7%) carcinomas. PDX1 and MUC6 double positive expression was observed in carcinomas, respectively, including the corpus, and also correlated with histological type and depth of invasion. In contrast, no link was apparent between PDX1 and MUC5AC double positive reactivity and histological type. CONCLUSION: Our study suggests that PDX1 plays an important role in the development of pseudopyloric glands, and that pseudopyloric glands may reflect a condition associated with gastric carcinogenesis.     

黏蛋白在胃癌的诊断和预后评估中的作用

黏蛋白是由特殊的上皮细胞分泌的大分子量糖蛋白。多项研究显示黏蛋白在不同胃黏膜病变尤其在胃腺癌的不同类型中存在不同的表达:MUC1、MUC5AC、MUC6在正常胃黏膜中呈强阳性表达而MUC2则不表达。在正常胃黏膜向肠上皮化生、胃癌演进过程中,MUC1、MUC5AC、MUC6表达呈下调趋势而MUC2表达上调。此文就胃腺癌的不同类型及其发展,黏蛋白在不同胃黏膜病变中的表达及其在胃腺癌的诊断和预后评估中的作用等做一概述。     

粘蛋白MUC1、MUC2、MUC4和MUC5AC在胰腺导管腺癌中的表达及意义

目的 研究胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDA)组织中粘蛋白MUC1、MUC2、MUC4和MUC5AC的表达及其与临床病理参数间的关系.方法 应用SP免疫组织化学方法检测26例PDA、4例CP、16例正常胰腺组织、2例导管内乳头状黏液性肿瘤(IPMN)、4例实性假乳头状瘤(SPT)和1例浆液性囊性肿瘤(SCN)组织中MUC1、MUC2、MUC4、MUCSAC的表达.结果 正常胰腺和CP组织仅有MUC1表达,表达率均为100%;PDA中MUC1、MUC4和MUC5AC表达率分别为100%、88.5%(23/26)和76.9%(20/26);2例IPMN均见MUC2和MUC5AC表达;SPT和SCN中4种粘蛋白均无表达.MUC4和MUC5AC表达同PDA的临床病理参数之间无相关性(P＞0.05).结论 PDA时存在多种粘蛋白的表达,联合检测MUC1、MUC2、MUC4和MUC5AC的表达可能有助于对PDA的诊断和鉴别诊断.     

The role of mucin in GERD and its complications

Acid, pepsin and other noxious material reach the esophageal mucosa and interact with the luminal aspect of the squamous epithelium. The first protective barrier to these potentially injurious substances is the mucus buffer layer that covers the mucosa. In healthy people, the esophagus has a protective surface adherent mucus gel barrier. Levels of mucin glycoprotein are considerably increased in response to acid and pepsin. A wide spectrum of mucin genes are expressed in normal esophageal mucosa, squamous cell carcinoma of the esophagus, Barrett epithelium and esophageal adenocarcinoma. The mucins MUC5AC and MUC6 are expressed to a similar degree in Barrett metaplasia and gastric mucosa, as is MUC2 in Barrett intestinal metaplasia and small bowel mucosa. Increased expression of MUC1 is associated with progression from dysplasia to adenocarcinoma of the esophagus. Thus, mucins have an important role in the defense of esophageal mucosa against the acid, pepsin and bile that are present in the refluxate. Changes in the expression of mucins occur in patients with GERD, and might lead to the development of new drugs.     

Infection with Helicobacter pylori Affects All Major Secretory Cell Populations in the Human Antrum

We have investigated how gastric H. pylori infection affects antrum secretory cell types by studying the expression of secretory proteins in antrum epithelium. Antrum biopsy specimens were prospectively collected from 102 individuals (49 H. pylori-infected). Immunohistochemistry was performed for secretory mucins (MUC5AC, MUC5B, MUC6), Trefoil factor family (TFF)-peptides (TFF1, TFF2), endocrine peptides (gastrin, chromogranin A), and proliferating cells (Ki-67). Protein expression was quantified morphometrically. H. pylori infection was significantly correlated to mucosal inflammation and to epithelial atrophy and proliferation. In H. pylori-infected patients the number of proliferating cells increased significantly, and the zone of proliferating cells shifted toward the surface epithelium of the antral glands. Infection was correlated with decreased MUC5AC, TFF1, and TFF2 expression and increased MUC6 and MUC5B expression. Endocrine cells expressing chromagranin A and gastrin shifted toward the surface epithelium of the antral glands in H. pylori-infected patients. H. pylori infection and concomitant inflammation induced increased epithelial proliferation and triggered coordinate deregulation of secretory cell populations in the antrum. In particular, infection led to a coordinated increase in cells expressing MUC6 and MUC5B at the expense of MUC5AC-producing cells.     

MUC1 and MUC5AC mucin expression in liver fluke-associated intrahepatic cholangiocarcinoma

AIM: To investigate the expressions of MUC1 and MUC5AC in intrahepatic cholangiocarcinoma (ICC). Association of expressions of mucins MUC1 and MUC5AC with clinical findings, metastasis, and survival of the liver fluke-associated ICC patients was determined. METHODS: The expressions of MUC1 and MUC5AC mucins were examined by immunohistochemical staining in 87 cases of histologically-proven ICC. The expressions of mucins in relationship between clinicopathological significance and prognosis of the patients were evaluated. RESULTS: Fifty-two patients (60%) exhibited both MUC1 and MUC5AC expressions, whereas 31% expressed either MUC1 or MUC5AC, and 9% expressed neither. High MUC1 immunoreactivity displayed a significant correlation with tumor progression as reflected by vascular invasion (P<0.01), whereas high expression of MUC5AC significantly correlated with neural invasion (P = 0.022) and advanced ICC stage (P= 0.008). Patients with high expression of MUC1 had a significantly shorter survival (P = 0.0002). According to multivariate analyses, MUC1 reactivity (P = 0.026), histological grading and stage of tumor represented the least probability of survival. CONCLUSION: MUC1 is overexpressed in liver fluke-associated cholangiocarcinoma and relates to vascular invasion and poor prognosis, whereas MUC5AC mucin is neoexpressed and relates to neural invasion and advanced ICC stage. High MUC1 expression in tumor may be useful for predicting the poor outcome of ICC patients.     

Gastric and intestinal differentiation in Barrett''s metaplasia and associated adenocarcinoma

Intestinal metaplasia is a prerequisite criterion for the diagnosis of Barrett's metaplasia and the sole columnar esophageal lining associated with malignancy. It is recognized by the presence of goblet cells, but columnar non-goblet elements, producing gastric or intestinal proteins, are the prevalent cell population. The cellular heterogeneity of Barrett's metaplasia is well documented but the relationship between the distinct cell subtypes and neoplasia is unclear. Our aim was to clarify the relationship between the different metaplastic populations and malignancy in order to investigate putative markers for risk stratification of Barrett's patients. We studied 46 columnar-lined esophageal segments, 15 with associated adenocarcinoma. The presence of the gastric, MUC5AC and MUC6, and the intestinal, MUC2, proteins was evaluated in metaplastic (columnar and goblet) and neoplastic cells. In neoplasia MUC5AC and MUC6 were detected in 100% and 86.6% of the cases, respectively. In metaplasia there were no differences in MUC5AC and MUC6 immunoreactivity, between cases with and without associated neoplasia, except for goblet elements producing MUC6 that were exclusive of metaplasia adjacent to adenocarcinoma (P < 0.05). MUC2 was present in 86.6% of the neoplasia. In metaplasia it was restricted to Barrett's cases and was more frequent in areas with intestinal metaplasia. Columnar-lined esophagus without intestinal metaplasia did not express MUC2. Our study suggests a relationship between the metaplastic population with gastric phenotype and malignancy, and points to the involvement of columnar as well as goblet elements in tumorigenesis. The association between goblet cells aberrantly producing MUC6 and the presence of neoplasia suggests they may be useful for risk stratification.     

Increased TFF1 trefoil protein expression in Opisthorchis viverrini-associated cholangiocarcinoma is important for invasive promotion

Aims: Cholangiocarcinoma (CCA) is a poor prognosis cancer that presents with metastatic disease. This cancer expresses MUC5AC, a mucin which normally co-expresses with trefoil factor family 1 (TFF1) protein. TFF1 is a signalling protein that can activate epithelial cell invasion and has been considered as a metastasis stimulating agent. The aim of this study was to determine the co-expression of TFF1 and MUC5AC in CCA tissues and examine the activity of TFF1 for stimulating the invasive property of CCA cell lines. Methods: In this study, TFF1 and MUC5AC were detected in CCA tissues by using immunohistochemistry. The correlations of both proteins expression with clinical data were analyzed. The activity of TFF1 was investigated using an in vitro invasion assay with established CCA cell lines KKU-100 and KKU-M213. Results: We demonstrated a high level of expression of TFF1 in 91.80% of CCA that is associated with a high level of co-expression with MUC5AC in 80.33% of cases. In vitro invasion assay showed that both cell lines have similar responses to TFF1 that could act as both a chemokinetic and chemotactic agent. The dose-response curves were bell-shaped. Conclusion: TFF1 showed co-expression with MUC5AC in CCA tissues and invasive stimulating activity in vitro. These results may indicate a role for TFF1 in promoting tumor invasion in CCA.     

Prognostic Significance of Mucin Expression in Gastric Carcinoma

In patients with gastric carcinomas, the role of the alteration of mucin expression in overall survival has been a matter of some speculation, but few studies have been reported. The aim of our study was to determine the relationship between MUC1, MUC2, and MUC5AC expression and patient survival, with a secondary aim designed to investigate the alteration of MUC expression within various clinicopathologic parameters. Forty-four specimens from gastric carcinoma patients were immunohistochemically evaluated using the monoclonal antibodies for MUC1 (EMA, clone E29), MUC2 (CCP58), and MUC5AC (human gastric mucin, clone 45M1). MUC1 expression increased in gastric carcinoma. MUC1 positivity was determined to be statistically significant, with poor clinicopathological parameters and decreased long-term survival. MUC5AC expression decreased in gastric carcinoma. In addition, patients with MUC5AC-positive tumors also had poor clinicopathological parameters and showed shorter survival than those with MUC5AC-negative tumors. MUC2 expression was not significantly associated with patient survival. We confirmed that the expression of mucins is associated with characteristics of differentiation in gastric carcinoma. Poor patient outcomes were seen in gastric carcinomas with MUC1 mucin expression and MUC5AC positivity.     

Immunohistochemical analysis of short-segment Barrett's esophagus

BACKGROUND AND AIMS: The majority of dysplasias and adenocarcinomas in Barrett's esophagus are closely associated with the specialized columnar epithelium. In this study, we performed an immunohistochemical analysis of columnar metaplasia presenting in short-segment Barrett's esophagus (SSBE). PATIENTS AND METHODS: The endoscopic biopsy specimens obtained from 91 patients were analyzed. Ten were cases of long-segment Barrett's esophagus (LSBE) and 81 had SSBE. Expression of MUC2, MUC5AC, Con A and CD10 was evaluated using immunohistochemical staining. RESULTS: All samples from LSBE (n = 9) were histologically diagnosed as specialized columnar epithelium. The 81 SSBE samples were divided into gastric fundic-type (n = 26), junctional-type (n = 16) and specialized columnar epithelium (n = 39). In the specialized columnar epithelium of SSBE, there was a predominance of goblet cell-type metaplasia proposed by Watanabe et al. which is characterized by MUC2-positive pyloric epithelium (66.7%). The total percentage of non-goblet cell-type and goblet cell-type was 76.9%. In contrast, 80% of LSBE revealed the large intestinal-type or the large and small intestinal-type. The long oval and villous pit by magnifying endoscope suggests the presence of the specialized columnar epithelium, but the phenotypic classification of Watanabe's criteria was not associated with the endoscopic pit pattern. CONCLUSION: Intestinal metaplasia in Barrett's esophagus changes immunohistochemically with progress of the disease.     

H pylori colocalises with MUC5AC in the human stomach

BACKGROUND: The bacterium Helicobacter pylori is able to adhere to and to colonise the human gastric epithelium, yet the primary gene product responsible as a receptor for its adherence has not been identified. AIMS: To investigate the expression of the gastric mucins MUC5AC and MUC6 in the gastric epithelium in relation to H pylori colonisation in order to examine their possible roles in the binding of H pylori. PATIENTS: Seventy two consecutive patients suspected of having H pylori infection. METHODS: MUC5AC, MUC6, and H pylori were detected in single sections of antral biopsy specimens using immunohistochemical triple staining. RESULTS: MUC5AC was expressed in the superficial epithelium and the upper part of the gastric pits. MUC6 expression was detected in the lower part of the gastric pits. The expression of both mucins in the epithelium was complementary. In each patient, there was a sharply delineated transition between MUC5AC and MUC6 producing cell populations. In all H pylori positive patients there was a striking colocalization of H pylori and MUC5AC; more than 99% of the bacteria were associated with either extracellular MUC5AC or the apical domain of MUC5AC producing cells. CONCLUSIONS: H pylori is very closely associated with extracellular MUC5AC and epithelial cells that produce MUC5AC. This indicates that MUC5AC, but not MUC6, plays a role in the adhesion of H pylori to the gastric mucosa.     

Expression of mucins and E-cadherin in gastric carcinoma and their clinical significance

AIM: To investigate the expression of three types of mucin(MUC1, MUC2, MUC5AC) and E-cadherin in human gastric carcinomas and their clinical significance. METHODS: Ninety-four gastric cancer specimens were classified according to WHO criteria and detected by immunohistochemical assay of expression of mucins and E-cadherin. RESULTS: The positive expression rates of MUC1, MUC2, MUC5AC and E-cadherin were 82% (77/94), 84% (79/94), 40% (38/94) and 56% (53/94) respectively. MUC1 expression was significantly correlated with the types of cancer (the positive rates of MUC1 in well and moderately differentiated tubular adenocardnoma, poorly differentiated adenocardnoma, signet-ring cell carcinoma and mucinous carcinoma were 91%, 87%, 71%, 71%, respectively, P&lt;0.05), age of patients (the positive rates of it among the people who are younger than 40 years, between 40-60 years and over 60 yearwere 74%, 81%, 89%, P&lt;0.05), lymph nodes involvement (the positive rates in the non-interfered group and the interfered group were 78%, 85%, P&lt;0.05) and tumor size (the positive rates in the tumors with the size less than 3 cm, 3-6 cm and larger than 6 cm were 69%, 92%, 69%, P&lt;0.05); MUC2 expression was significantly associated with types of cancers and had the strongest expression in mucinous carcinomas (the posrdve rates of MUC2 in well and moderately differentiated tubular adenocardnoma, poorly differentiated adenocardnoma,signet-ring cell carcinoma and mucinous carcinoma were 94%, 70%, 81%, 100%, P&lt;0.05), but it had no obvious relation to age, gender, tumor location, lymph nodes involvement,depth of invasion and metastasis to extra-gastric organs (P&gt;0.05); MUC5AC expression was not related to any of the characteristics investigated except that it had relation to gender, whereas MUC5AC showed the tendency to higher expression in less invasive lesions and lower expression in advanced stage cancers (P&gt;0.05); No significant difference was found for E-cadherin expression. There were strong positive relationships between the expression of MUC1 and E-cadherin, MUC2 and E-cadherin, MUC1 and MUC2(R=0.33, R=0.22, R=0.32, respectively, P&lt;0.05). According to the COX proportional hazards model, older patients, involvement of lymph nodes, different types of gastri ccancer and MUC2 expression were significantly associated with poorer outcome of gastric carcinoma patients (β=0.08,β=3.94, β=1.33, β=0.75, respectively, P&lt;0.05). CONCLUSION: MUC1 and MUC2 are good markers of different types of gastric cancer. MUC2 is especially a good marker of mucinous carcinoma. MUCl, MUC2 may interfere with the function of E-cadherin in gastric carcinomas, and have synergic effect on progression of gastric cancers.     

Expression of MUC5AC and MUC5B mucins in normal and cystic fibrosis lung

Hypersecretion of airway mucus is a characteristic feature of chronic airway diseases like cystic fibrosis (CF) and leads via impairment of the muco-ciliary clearance and bacterial superinfection to respiratory failure. The major components of the mucus matrix forming family of mucins in the airways are MUC5AC and MUC5B. To investigate the expression of these glycoproteins in CF, immunohistochemistry was carried out on trachea, bronchi and peripheral lung obtained from CF patients and compared to normal lung tissues. MUC5AC immunohistochemistry demonstrated signals in goblet cells of the epithelial lining. Also, goblet cells inside glandular secretory ducts revealed MUC5AC-positive staining. In comparison to those from normal subjects, CF sections were characterized by inflammatory changes and goblet cell hyperplasia, resulting in increased numbers of MUC5AC-positive cells. Immunohistochemical staining for MUC5B showed abundant staining of submucosal glands and epithelial goblet cells. Inside the glands, the immunoreactivity was restricted to glandular mucous cells. MUC5AC and MUC5B are expressed in the same histological pattern in CF compared to normal tissues with an increase of MUC5AC-positive cells due to goblet cell hyper- and metaplasia.