Significance of MUC1 and MUC2 mucin expression in colorectal cancer.

AIMS: To compare the lineage specific distribution of MUC1 and MUC2 mucins in normal colorectal mucosa and adenocarcinoma and to identify pathological correlations. METHODS: Paraffin wax sections from 51 colorectal cancers were examined for the expression of MUC1 and MUC2, non-O-acetyl sialic acid and the carbohydrate epitopes Lex, Ley, sialosyl-Lex, sialosyl-Tn, and Tn using standard histochemical methods. RESULTS: MUC1, Lex and Ley co-localised with columnar cell secretions, whereas MUC2, mild periodic acid Schiff and sialosyl-Tn co-localised with goblet cell mucin in both normal and malignant tissues. Sialosyl-Lex and Tn were associated with both lineages. In normal tissues MUC1, Lex and Ley showed only trace expression by crypt base columnar cells. Cancers could be classified into four phenotypes (MUC2+/MUC1-, MUC2+/MUC1+, MUC2-/MUC1+, MUC2-/MUC1-). Particular phenotypes showed significant correlations with cancer type, lymph node spread and peritumoral lymphocytic infiltration and trends falling short of significance in relation to grade of differentiation and contiguous adenoma. CONCLUSIONS: Classification of colorectal cancer by means of lineage specific function may be relevant to both pathogenesis and prognosis.     

Simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn, T and sialosyl-T) and gp 230 mucin-like glycoprotein are candidate markers for neoplastic transformation of the human cervix

Mucins and simple mucin-type carbohydrates are cancer-associated antigens in several human tumors. Expression of Tn, sialosyl-Tn, Thomsen-Friedenreich (T), sialosyl-T and of a recently identified mucin-like glycoprotein (gp230) has not yet been thoroughly investigated in human cervix carcinogenesis. In the present study sections from normal cervix (n=10), CIN III lesions (n=10), and invasive carcinomas (n=47) were evaluated immunohistochemically using monoclonal antibodies. In normal cervix there was: cytoplasmatic expression of Tn in 1 case (10%); membranous expression of STn in 8 cases (80%); no expression of T and cytoplasmatic expression of ST in 1 case (10%); gp 230 was expressed in all cases with a membranous pattern. In CIN III lesions there was cytoplasmatic and membranous expression of Tn in 3 cases (30%) and of STn in 9 cases (90%); T and ST were not expressed; gp 230 was expressed in 5 cases (50%) both in the cytoplasm and at the cell membrane. In invasive carcinomas we observed Tn expression in 30 cases (63.8%) and STn in 31 cases (66%); T antigen was not expressed; expression of both ST and gp 230 in 24 cases (51.1%); all antigens showed membranous and cytoplasmatic staining. Our results show that Tn and ST are good markers of invasive carcinomas of the human cervix. We have also shown that loss of expression of the mucin-like glycoprotein gp 230 is associated with malignant transformation at a preinvasive stage. Received: 16 December 1999 / Accepted: 9 February 2000     

Immunodetection of epithelial mucin (MUC1, MUC3) and mucin-associated glycotopes (TF, Tn, and sialosyl-Tn) in benign and malignant lesions of colonic epithelium: apolar localization corresponds to malignant transformation

 Epithelial mucins are present at the apical membranes of gastrointestinal epithelial cells or in their secretions. In this study, we examined the occurrence of peptide epitopes of the mucins MUC1 and MUC3 and of three mucin-associated glycotopes (TF, Tn, and s-Tn) in a series of colorectal tissue samples (normal colon, adenomas with different grades of dysplasia, carcinoma in situ, and invasive carcinomas). A new monoclonal antibody to a conformation-dependent peptide epitope of MUC1 was employed, which does not react with the fully glycosylated mucin as found in normal gastrointestinal mucosa. We found that adenomas acquired the ability to expose Tn, s-Tn, TF and MUC1 epitopes, and this correlated with increasing malignant potential. The secretory mucin, MUC3, revealed a different pattern: it was detectable in all sections, with maximum expression in adenomas and decrease in carcinomas. Most importantly, normal mucosa and benign lesions showed supranuclear and/or apical distribution of these antigens, but malignant lesions and lesions with a very high risk of malignancy revealed diffuse cytoplasmic and basolateral membrane localization. The immunohistological response to a combination of MUC1-related antibodies may assist in assessing the malignant potential and status of lesions of the colon. Received: 18 February 1997 / Accepted: 2 April 1997     

Expression of MUC1 and MUC2 and carbohydrate antigen Tn change during malignant transformation of biliary papillomatosis

AIM: Biliary papillomatosis is characterized by papillary proliferations of biliary lining cells without invasion or metastasis. The neoplastic character and biological behaviour of this disease remain still speculative. These issues were examined in this study. METHODS AND RESULTS: Mucin core protein MUC1, MUC2, MUC3, MUC5AC and carbohydrate antigens (T, Tn and sialosyl Tn) were immunohistochemically examined, using 11 lesions of biliary papillomatosis from seven patients, and five lesions of biliary papillomatosis with foci of carcinoma from four patients. Five cases of papillary intrahepatic cholangiocarcinoma and 12 histologically normal livers were used as a control. Patients with biliary papillomatosis alone or with carcinoma were middle-aged or elderly (five men and six women). Microscopically, biliary papillomatosis showed a villous, papillo-tubular, papillary, or papillo-villous pattern with a thin fibrovascular core. Cytologically, they were classifiable into biliary epithelial or pyloric gland-like type. The former was frequent in the cases associated with carcinoma. Expression of MUC1, Tn antigen and sialosyl Tn antigen was frequent and marked in biliary papillomatosis alone and with carcinoma and also intrahepatic papillary carcinoma. In addition, marked expression of MUC1 and Tn antigen were rather frequent in biliary papillomatosis with carcinoma and intrahepatic biliary papillary carcinoma compared with biliary papillomatosis. MUC2 was rather frequent and marked in biliary papillomatosis alone compared to other two disease groups. Focal expression of MUC5AC and MUC2 was rather frequent and infrequent irrespective of disease group, respectively. Focal expression of T antigen was frequent in papillary ICC. CONCLUSION: Biliary papillomatosis could undergo overt malignant transformation along with altered phenotypic expression of MUC proteins and mucin carbohydrate antigens.     

气道上皮杯状细胞化生和分泌调控

杯状细胞化生及黏液过度分泌是气道慢性炎症的重要病理改变,气管支气管树杯状细胞化生是黏蛋白的主要来源也是黏液过度分泌的结构基础。杯状细胞主要分泌黏蛋白5AC。感染因素、炎症/免疫反应介质、蛋白酶、内、外化合物等均可诱导黏蛋白5AC转录并可能参与转录后水平的分泌调控,表皮生长因子受体信号转导通路是诱导MUC5AC基因表达的主要通路。不同刺激物诱导杯状细胞增生和化生,气道上皮细胞如纤毛细胞和Clara细胞等可转分化成杯状细胞,目前认为杯状细胞化生的关键介导环节涉及白介素-13 和表皮生长因子受体,而Bcl-2则与化生杯状细胞寿命的维持有关。     

Characterization and heterogeneity of monoclonal antibodies directed to intestinal mucin derived from Crohn's disease small bowel

A panel of 12 monoclonal antibodies were produced by immunization of Balb/c mice with small bowel epithelial cells obtained from a patient with active well-documented Crohn's disease. The clones were derived by screening with immunofluorescence microscopy; those with staining patterns suggestive of mucin directed epitopes were chosen for study. Several distinct patterns of staining reactivity were noted, including reagents with homogeneous, luminal, heterogeneous and peripheral goblet cell activity. In addition, SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis revealed reactivity to high molecular weight mucin. The reactive antigen was resistant to proteinase digestion. No endoneuraminidase activity was detected; however, one neuraminidase sensitive sialic acid epitope was demonstrated. Confirmation of glycoprotein epitopes was accomplished by testing purified mucins from several areas of the gastrointestinal tract by ELISA. Finally, individual small bowel goblet cell heterogeneity was demonstrated by immunofluorescence, Western blotting, and antibody affinity chromatography. These data demonstrate both by morphology and specific binding of antibody affinity chromatography a significant degree of small bowel goblet cell mucin heterogeneity.     

Colorectal mucin histochemistry in health and disease: A critical review

Neoplastic, inflammatory and regenerative processes affecting colorectal mucosa are associated with alterations in structure of epithelial mucin. This review collates mucin-, lectin-, and immuno-histochemical observations on colorectal mucins and introduces recent molecular genetic insights into the structure of the protein backbone of mucins. The numerous structural modifications uncovered by the various technical approaches have been reduced to a few manageable principles that are of relevance to both researcher and diagnostic pathologist. Particular attention is drawn to the need to appreciate the limited specificities of probes, the confounding influences of anatomical site and genetic factors (necessitating the use of appropriate positive and negative control tissues) and the precise location of secretory material. In the past, insufficient attention has been given to the effects of altered differentiation including metaplasia and differing lineage expression in epithelial disorders of growth. It is likely that certain changes loosely ascribed to goblet cell mucin, such as neo-expression of blood group antigens and anomalous expression of core carbohydrate structures, do not occur at all. Critical examination of available data point to only two consistent and unequivocal changes affecting goblet cell mucin in pathological processes: loss of O-acetyl substituents at sialic acid C₄ and C_7,8,9 and increased sialyla-tion. Furthermore, there are no neoplasia-specific alterations in mucins documented to date. All neoplasia-associated changes have been described in non-neoplastic lesions also.     

Differences in the expression of mucins in various forms of cystitis glandularis

A wide spectrum of glandular epithelial metaplastic changes may be seen in the bladder. Cystitis glandularis (CG) is a well-known metaplastic lesion occurring in the presence of chronic inflammation, but there are a few data about mucin expression in its two subtypes (typical and intestinal). The purpose of the present study was to determine the expression of mucin core proteins and CD10 in the different types of CG. For this examination, we used a panel of monoclonal-specific antibodies for MUC1, MUC2, MUC5AC, and MUC6. CG of the intestinal type expressed MUC5AC both in goblet and columnar cells, and strongly expressed intestinal mucin MUC2 only in goblet cells in all cases. There was no expression of MUC1, MUC6, and CD10 in the metaplastic cells. CG of the typical type showed an expression of MUC1 similar to normal urothelium, but the CD10 expression was more intensive than in the control. The mucin expression profile in the different types of CG allows the identification of "gastric mucin" (MUC5AC) together with intestinal mucin (MUC2), while typical CG (CGTP) retains MUC1. Different and contrasting immunoprofiles were evident in various forms of CG. The absence of CD 10 in CG of the intestinal type is a finding that points towards an incomplete form of urinary bladder metaplasia.     

Colonic mucin-carbohydrate components in colorectal tumors and their possible relationship to MUC2, p53 and DCC immunoreactivities

To clarify changes in mucus components during colorectal tumorigenesis, we developed novel monoclonal antibodies (Abs) against carbohydrate chains of human colorectal mucin (HCM) obtained from normal sigmoid and rectal mucosae. A hundred and ninety-nine cases of colorectal carcinoma and 67 cases of tubular adenoma, along with 250 normal colonic tissue samples, were investigated immunohistochemically. The results were compared with clinical stage, survival and MUC2 (core protein of the intestinal type mucin) expression, as well as with the status of the p53 and DCC (deleted in colorectal carcinomas) genes. In the normal colonic epithelium, HCM14 Ab reacted with the cytoplasmic regions of the goblet cells and enterocytes, while HCM21 Ab bound to mucous droplets in the former, suggesting a more mature carbohydrate structure. Both HCM14 and 21 scores were significantly decreased in adenomas and carcinomas. This is in line with an altered PAS-Alcian blue staining, indicating accumulation of mucins with incomplete or abnormal glycosylation in tumors. Levels of HCM14 and 21 binding tended to show a positive correlation with expression of MUC2 and DCC, and a negative association with p53 protein accumulation in carcinomas, although there was no apparent link to Duke's stage or the prognostic outcome. These findings suggest a possible involvement of alterations in mucin carbohydrate in colorectal tumor development. The observed changes may be associated with loss of MUC2 and DCC expression, as well as with p53 protein accumulation.     

Expression of MUC1, Thomsen-Friedenreich antigen, Tn, sialosyl-Tn, and α2,6-linked sialic acid in hepatocellular carcinomas and preneoplastic hepatocellular lesions

The expression of epithelial mucins and Thomsen-Friedenreich-related antigens in preneoplastic and neoplastic hepatocellular lesions was systematically investigated using an in situ immunohistochemical staining approach. MUC1, MUC2, TF, sialosyl-TF, Tn, sialosyl-Tn, alpha2,3-linked sialic acid, and alpha2,6-linked sialic acid were examined in normal and cirrhotic human liver and in human hepatocellular carcinomas (HCCs) and cholangiocarcinomas. Normal hepatocytes and preneoplastic foci of altered hepatocytes did not express MUC1, MUC2, TF, Tn, s-Tn, or alpha2,6-linked sialic acid. In contrast, HCCs showed positive reactions for MUC1, TF, Tn, s-Tn, and alpha2,6-linked sialic acid. MUC2 was absent in normal biliary epithelial cells, but present in cholangiocarcinomas. The staining of MUC1, or s-Tn and alpha2,6-linked sialic acid in human normal liver tissues and various liver diseases did not change after specific treatments such as periodate oxidation or saponification, indicating that their expression in HCC does not result from incomplete glycosylation or low O-acetylation, respectively. MUC1, TF, Tn, s-Tn, and alpha2,6-linked sialic acid may be useful as indicators of progression of HCC in tissue sections, and perhaps also as targets for diagnostic and therapeutic approaches in vivo.     

Sialosyl-Tn expression in normal and pathological conditions of human endometrium. An immunohistochemical study

To assess the clinico-prognostic relevance of the cell surface carbohydrate glycoprotein in normal and pathological conditions of human endometrium, Sialosyl-Tn (STn) antigen was immunohistochemically studied in normal (n = 10), hyperplastic (n = 18), and neoplastic (n = 60) endometrial lesions. There was no STn antigen reactivity in the proliferative endometrial slides, while weak staining was observed in all secretory endometria. STn expression was noted in 8/18 (44%) hyperplastic endometrial cases and in 40/60 (67%) endometrial carcinomas. Positive staining was observed throughout the cytoplasm of the glandular cancer cells, at the cell membranes, and in an intraluminar mucus. This antigen was mostly expressed heterogeneously as far as the distribution of positive cells is concerned. There was a statistically significant association between STn expression and the histological grading of cancer (p = 0.019). Advanced clinical stage (III-IV; p = 0.014) and infiltration of the myometrial wall (more than 1/2 of the myometrial wall; p = 0.004), but no STn immunoreactivity, were reported to be independent prognostic variables during follow-up. Our study shows that a) STn is not constantly expressed during the menstrual cycle, and is increased at the secretory phase of the cycle; b) Sialosyl-Tn reactivity decreases with the degree of tumor differentiation, but there was no relationship with other clinicopathological variables of cancer; c) this cell surface carbohydrate glycoprotein does not appear to predict the outcome of endometrial cancer patients.     

Non-glycosylated tandem repeats of MUC1 facilitate attachment of breast tumor cells to normal human lung tissue and immobilized extracellular matrix proteins (ECM) in vitro: potential role in metastasis

MUC1 is a transmembrane glycoprotein abundantly expressed on the apical surface of human ductal epithelial cells and over entire cell surface of tumors originating from those cells. It is 300 to 500 nm long and has a rigid, rod-like structure protruding from the cell surface. MUC1 expressed by normal cells has heavily O-glycosylated tandem repeat domain while MUC1 on malignant cells is aberrantly O-glycosylated. Substantially reduced (aberrant) glycosylation of the tandem repeat region of tumor MUC1 results in uncovering of the polypeptide core. This new structural feature may play an important role in the attachment of metastasizing tumor cells to tissues at distant sites. We show that MDA-MB-231 cells attaching to the immobilized extracellular matrix proteins (ECM) are higher MUC1 expressers than those non-attaching and that the attachment is inhibited by the addition of non-glycosylated, MUC1 peptide. This 100 a.a. peptide composed of 5 tandem repeats from the tandem repeat domain mimics the forms of MUC1 found in ascites fluid of cancer patients. We also show that this synthetic form of MUC1 inhibited attachment of breast tumor cells to sections of normal human lung tissue and immobilized ECM. We did not find correlation between the expression of Tn (GalNAc-Ser/Thr) epitope and the ability of tumor cells to adhere to the immobilized ECM. These results indicate that the non-glycosylated form of MUC1 plays a role in the initial attachment of carcinoma cells to tissues at distant sites, which may facilitate establishment of metastatic foci. This revised version was published online in July 2006 with corrections to the Cover Date.     

Simple mucin-type carbohydrate antigens (T, Tn and sialosyl-Tn) in mucoepidermoid carcinoma of the salivary glands

Thirty-two cases of mucoepidermoid carcinoma of the salivary glands were studied in order to characterize the expression of simple mucin-type carbohydrate antigens T, Tn and sialosyl-Tn and to evaluate its implication for tumour histogenesis. Monoclonal antibodies of known specificity were used on formalin-fixed, paraffin-embedded tissue, and the expression of these antigens was studied in each of the three cell types (mucous, intermediate and squamous) as well as in the secretory content of neoplastic lumina. Aberrant glycosylation of simple-mucin type antigens was found in all cell types, as compared with that of normal excretory duct cells of the salivary glands. The more 'primitive' antigens Tn and sialosyl-Tn were present in a high percentage of epidermoid and intermediate cells. Mucous cells and the intraluminal secretory content also expressed Tn in 57.7% of the cases. This contrasts with the absence of secretion of these simple mucin type carbohydrates by normal salivary gland cells. Mucin-producing cells did not express T antigen but only sialosyl-T, in contrast to 57.1% and 56.3% respectively of the epidermoid and intermediate cell types. T and sialosyl-T were also found in the secretory products of the neoplastic lumina in 11.5% and 53.6% of the cases, respectively. The distinctive glycosylation pattern between mucin-producing cells on the one hand and intermediate and squamous cells on the other does not contradict the common origin of the three cell types from the reserve cell of the salivary excretory duct, but favours the proposition that intermediate cells constitute a step in the differentiation pathway of epidermoid, but not of mucin-producing. cells.     

The expression of Tn and S-Tn antigens in cancer and pre-malignant lesion of colorectal tissues by enzyme immunohistochemical method

Expression of Tn and S-Tn antigens was examined by enzyme immunohistochemical SABC method in cancer, adenoma, hyperplastic polyps, normal adult and fetal colorectal tissues. Both antigens were proved to be oncofetal colorectal cancer-associated. S-Tn was considered to be the better marker, which give no expression in normal adult colorectal tissues, but does express in 81.3% of the cancer tissues, as well as in adenoma. S-Tn increased parallelly with the development of malignant potential changes, such as increasing of size, degree of dysplasia, and increase of villous histological patterns. Experimental data also demonstrated that in colonic cancer cells, a special sialic acid transferase, which is not existent in normal adult colon epithelium, partly changes Tn antigen to S-Tn; thus, T, Tn, and S-Tn antigens are possible to be coexistent in colorectal carcinoma.     

Aberrant Cosmc genes result in Tn antigen expression in human colorectal carcinoma cell line HT-29

The Tn antigen, which arises from mutation in the Cosmc gene is one of the most common tumor associated carbohydrate antigens. Cosmc resides in X24 encoded by a single gene and functions as a specific molecular chaperone for T-synthase. While the Tn antigen cannot be detected in normal cells, Cosmc mutations inactivate T-synthase and consequently result in Tn antigen expression within certain cancers. In addition to this Cosmc mutation-induced expression, the Tn antigen is also expressed in such cell lines as Jurkat T, LSC and LS174T. Whether the Cosmc mutation is present in the colon cancer cell line HT-29 is still unclear. Here, we isolate HT-29-Tn⁺ cells from HT-29 cells derived from a female colon cancer patient. These HT-29-Tn⁺ cells show a loss of the Cosmc gene coding sequence (CDS) leading to an absence of T-synthase activity and Tn antigen expression. Additionally, almost no methylation of Cosmc CpG islands was detected in HT-29-Tn⁺ as well as in HT-29-Tn^- and Tn^- tumor cells from male patients. In contrast, the methylation frequency of CpG island of Cosmc in normal female cells was ~50%. Only one active allele of Cosmc existed in HT-29-Tn⁺ and HT-29-Tn^- cells as based upon detection of SNP sites. These results indicate that Tn antigens expression and T-synthase inactivity in HT-29-Tn⁺ cells can be related to the absence of CDS in Cosmc active alleles, while an inactive allele deletion of Cosmc in HT-29 cells has no influence on Cosmc function.     

Expression of the Tn antigen on erythroid cells from a patient with Tn syndrome

Summary In order to examine expression of the Tn antigen on erythroid cells from a patient with Tn syndrome, we applied a selective two phase liquid culture system for human erythroid progenitors in peripheral blood. The cells were analyzed with flow cytometry employing an anti-Tn antibody and a lectin ofVicia villosa which recognizes only the Tn determinant. In the second phase, the Tn antigen was expressed on the cultured cells from the patient on day 3 and Tn-positive cells reached 62.7% on day 9. On the other hand, Tn-positive cells were not detected in the volunteer's cultured cells. When the patient's cells were co-cultured with the cells from a healthy voluteer, the percentage of Tn-positive cells was much lower than the expected value, suggesting that the normal cells suppressed the expression of Tn antigen on the patient's cells.     

Histochemical comparison of the epithelial mucins in the ileum in Crohn''s disease and in normal controls.

A comparison of routine and special histochemical methods that were applied to the epithelial mucins of small intestine from patients with Crohn's disease and from normal controls showed that the normal small intestine (ileum) goblet cells secrete a predominantly non-sulphated sialomucin and that, in contradistinction to the colon, the neuraminidase insensitivity of the sialic acids of the small intestine was not due to either O-acylation at C4 or an ester substituent at C1. Presumably this implies that the protection against enzyme attack afforded to the mucosa by the mucin coat in the small intestine utilises a different mechanism from that in the colon and that, although in many respects the small intestinal mucins in Crohn's disease, and in normal controls are similar, there is an increase in side-chain O-acylated sialic acids in such mucins in Crohn's disease. This difference has not been described before, probably because it can be seen only after staining such sections by the PAT/KOH/PAS and the PBT/KOH/PAS techniques.     

The immunoexpression of Tn, sialyl-Tn and T antigens in chronic active gastritis in relation to Helicobacter pylori infection

The simple mucin-type carbohydrate antigens Tn, sialyl-Tn and T represent the mucin core oligosaccharide structures that are produced in the initial steps of mucin biosynthetic pathway. Utilising monoclonal antibodies anti-Tn antigen, anti-sialyl-Tn antigen and anti-T antigen, we have investigated the expression of the simple mucin-type carbohydrate antigens in 47 biopsy specimens of antral mucosa with chronic active gastritis, 25 of which had Helicobacter pylori infection. The Tn immunoreactivity, localised at the supranuclear region of surface and glandular mucous cells, was observed in all samples, independently from H. pylori status. The sialyl-Tn antigen, mainly localised in the cytoplasm of glandular mucous cells and in goblet cells vacuoles, was seen in 56% of the cases with H. pylori infection and in 41% of the cases in the H. pylori-negative group. In addition, the T antigen was found in the cytoplasm of surface and glandular mucous cells in 16% of the H. pylori-positive group, whereas the percentage of positive cases was reduced to 5% in H. pylori-negative patients, with an exclusive localisation in the cytoplasm of glandular mucous cells; after neuraminidase treatment, the percentage of T antigen-positive cases was increased to 28% in H. pylori-positive cases and to 27% in negative cases. No significant relationships between H. pylori infection and Tn, sialyl-Tn or T antigen immunoexpression were encountered in our cases. Therefore, we maintain that the inflammatory infiltrate may itself play an important role in the expression of simple mucin-type carbohydrate antigens in chronic active antral gastritis.     

Expression of aberrantly glycosylated Mucin-1 in ovarian cancer

Van Elssen C H M J, Frings P W H, Bot F J, Van de Vijver K K, Huls M B, Meek B, Hupperets P, Germeraad W T V & Bos G M J
(2010) Histopathology 57 , 597–606
Expression of aberrantly glycosylated Mucin‐1 in ovarian cancer Aims: Mucin 1 (MUC1) is an important tumour‐associated antigen (TAA), both overexpressed and aberrantly glycosylated in adenocarcinomas. The aim of this study was to examine the MUC1‐glycosylation status of primary ovarian adenocarcinomas and metastatic lesions. Methods and results: Paraffin‐embedded tissue sections of 37 primary ovarian adenocarcinomas representing all histotypes (22 serous, five mucinous, two clear‐cell, eight endometrioid), four serous borderline tumours with intraepithelial carcinoma, seven sections of ovarian endometriosis and 13 metastatic lesions were analysed by immunohistochemistry. Non‐neoplastic ovarian surface epithelium and serous cystadenomas were used as controls. All epithelia expressed MUC1 protein. Of primary tumours, 76% expressed the differentiation‐dependent glycoform and 84% the cancer‐associated glycoform (Tn/Sialyl‐Tn‐epitopes). In metastatic lesions this was 77% and 85%, respectively. Notably, in 57% of ovarian endometriosis and 75% of intraepithelial lesions, the cancer‐associated MUC1 epitopes were expressed, whereas normal ovarian surface epithelium and serous cystadenomas did not express these epitopes. Conclusions: The underglycosylated MUC1 epitopes are expressed by all histotypes of primary ovarian adenocarcinomas, by the vast majority of metastatic lesions and by possible ovarian cancer precursor lesions, but not by normal ovarian tissue. These results indicate that MUC1‐associated Tn/STn‐epitopes are important targets for immunotherapy and diagnostic imaging in ovarian cancer patients.