Immunohistochemical localisation of pS2 protein in ductal carcinoma in situ and benign lesions of the breast

Abstract

Summary The expression of pS2 was examined histochemically in paraffin sections taken from biopsy material from patients diagnosed with ductal carcincoma in situ (DCIS). Often intense immunoreactivity, to an anti-pS2 monoclonal antibody, was observed in comedo, solid, cribriform and micropapillary types of DCIS, with significant positivity found in 63-67% of cases. In 15 samples analysed, we found a good correlation between pS2 expression and presence of progesterone receptor positive cells, but not with estrogen receptor. There was only a limited degree of correspondence between the cells staining with these anti-sera. Some pS2 positive cells were also seen in normal acini in areas adjacent to cancer but much less frequently in sections of normal breast from reduction mammoplasty. Most normal areas were negative, as were cysts. In benign proliferative conditions (seen in sections with and without DCIS) such as adenosis, sclerosing adenosis, mild and florid ductal epithelial hyperplasia, significant pS2 positivity was seen in about 50% of cases.These results suggest that there is a progressive increase in pS2 from normal to benign to cancer cells and that this gene is expressed in both the invasive and pre-invasive forms of breast cancer.The pS2 gene, which was originally isolated by virtue of its estrogen-inducibility (Masiakowski et al., 1982), has been shown to be predominantly associated with estrogen receptor (ER) positive breast cancers (Rio et al., 1987;Skilton et al., 1989;Henry et al., 1989). Limited pS2 immunostaining has also been reported in normal breast and in parts of the ileum (Piggott et al., 1991;Luqmani et al., 1992), as well as more extensive expression in the stomach, but is otherwise absent from the vast majority of normal tissues. It is however, widely expressed in other epithelial cancers Luqmani et al., 1989;Rio et al., 1988; Luqmani et al., 1991;Wysocki et al., 1990) as well as in inflammatory conditions of the gastro-intestinal tract Seitz et al., 1992). pS2 has significant sequence homology with the (pancreatic) spasmolytic polypeptide (hSP) Wright et al., 1990) with which it is co-expressed in gastric mucosa (Theisinger et al., 1991) and is also secreted into the gastric fluid (Rio et al., 1988).In a small study we have recently (Shousha et al., manuscript submitted) found pS2 to have no prognostic significance in patients with colo-rectal cancer, but high pS2 levels were predictive of both longer survival (Foekens et al., 1990) and favourable response of breast cancer patients to endocrine therapy (Henry et al., 1989;Skilton et al., 1989) and, in this regard, may be superior to ER (Schwartz et al., 1991). Little is known of the expression of pS2 in early breast cancer. We therefore carried out an immunohistochemical study using archival material obtained from patients who had been diagnosed with ductal carcinoma in situ (DCIS), a neoplastic condition in which the malignant cells are confined within the basement membranes of the mammary ducts. This is believed to constitute a fore...

Relationship of PS2 with response to tamoxifen therapy in patients with recurrent breast cancer

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