Mucin expression in mucinous carcinoma and other invasive carcinomas of the breast
Introduction
Mucins are a family of heavily glycosylated, high molecular weight glycoproteins [1]. In humans, nine epithelial mucin genes (MUC 1, 2, 3, 4, 5A/C, 5B, 6, 7, 8) have been cloned [2]. All epithelial mucins produced by these genes contain a variable number of tandem repeats (VNTR) in the core protein. Mucin genes are independently regulated and their expression is organ and cell-type specific [3]. Mucins contain many different carbohydrate chains. These variations can occur due to incomplete or blocked synthesis or to neosynthesis. Increased synthesis, secretion, and alterations in glycosylation of mucin are believed to play important roles in tumor cells [4], [5]. The alterations in glycosylation lead to the appearance of novel structures, such as the epitopes recognized by monoclonal antibody CA50 (CA 50 epitope) and CA19-9 (sialyl Lewisa).
MUC1 is an integral part of the cell membrane in normal breast epithelium, and increased MUC1 expression is usually observed in breast cancer [6], [7], [8], [9], [10], [11]. MUC2, a secretory glycoprotein, is present in the small intestine and colon epithelia. Little or no expression of MUC2 is detected in epithelia outside the gastrointestinal tract. Overexpression of MUC2 was often found in colorectal cancer [12], [13] and gastric cancer [14], especially in the histologic type, mucinous carcinoma. MUC2 was not often detected in the usual ductal type of breast cancer [15]. The CA125 antigen is a glycoprotein present in most cases of ovarian carcinoma [16]. The gene codes for human gastric mucin (MUC6) are highly expressed in the stomach and gallbladder [17].
Breast cancer is a heterogeneous disease regarding morphology, invasive behavior, metastatic capacity, hormone receptor expression and clinical outcome. Mucinous carcinoma is a specific histologic type of breast cancer characterized by abundant extracellular mucin. The reported frequency of mucinous carcinoma of the breast is about 1–6% [18], [19]. It is generally thought that the tumor occurs in elderly women and has a better prognosis than the usual ductal type of breast cancer [20], [21].
For evaluating the mucin expression between mucinous and non-mucinous invasive breast cancer, we performed immunohistochemical staining using a panel of monoclonal antibodies and the result showed that mucinous carcinoma has a distinct pattern of mucin expression from other invasive breast carcinomas.
Section snippets
Materials and methods
Data on patients who had primary mucinous carcinoma of the breast were found in the records of the Department of Pathology at the National Taiwan University Hospital from 1978 to 1995. The tumors were histologically verified as mucinous carcinomas when nearly all the tumor cells were floating in abundant extracellular mucin. In total, there were 30 mucinous carcinomas. Ninety-five non-mucinous carcinomas (81 invasive ductal carcinomas, 6 invasive lobular carcinomas and 8 medullary carcinomas)
Results
The clinicopathologic characteristics of 30 mucinous carcinomas and 81 invasive ductal carcinomas of the breast are listed in Table 1. Mucinous carcinoma had a higher frequency of positive ER, high p27 expression and a lower frequency of axillary node metastasis and p53 overexpression than invasive ductal carcinoma.
In normal breast tissue, MUC1, CA19-9 and CA50 expression occurred in the apical cell membrane of epithelial cells, but MUC2, CA125 and human gastric mucin did not. The expression of
Discussion
We found a very high frequency of strong MUC2 expression in mucinous carcinoma compared with other histologic types of invasive breast carcinoma. Strong expression of MUC2 was observed in 72% of the mucinous but only in 21% of non-mucinous colonic carcinoma [12]. The MUC2 expression occurs in the premalignant stage and remains a characteristic property of the mucinous phenotype of colon tumors. The mechanisms of MUC2 overexpression in mucinous carcinomas are not known. Triggering the signal
Acknowledgements
This study was supported by the National Science Council, Taiwan. (grant no. 87-2314-B-002-320).
References (33)
- et al.
Is episialin/MUC1 involved in breast cancer progression?
Cancer Lett.
(1995) - et al.
Human gastric mucin. Identification of a unique species by expression cloning
J. Biol. Chem.
(1993) - et al.
Pure and mixed mucinous carcinomas of the breast
Hum. Pathol.
(1989) - et al.
Regulated expression of an intestinal mucin gene in HT29 colonic carcinoma cells
J. Biol. Chem.
(1993) - et al.
Mucins secreted by cell lines derived from colorectal mucinous carcinoma and adenocarcinoma
Eur. J. Cancer
(1997) - et al.
Mucins: structure, function, and associations with malignancy
BioEssays
(1992) - et al.
Mucin gene structure and expression: protection vs. adhesion
Am. J. Physiol.
(1995) - et al.
Heterogeneity of mucin gene expression in normal and neoplastic tissues
Cancer Res.
(1993) - et al.
Polymorphic epithelial mucin and CA125-bearing glycoprotein in basic and applied carcinoma research
Cancer Rev.
(1988) - et al.
The prognostic significance of two epithelial membrane antigens expressed by human mammary carcinomas
Int. J. Cancer
(1984)