BMC Cancer 2009, 9:251 http://www.biomedcentral.com/1471-2407/9/251 number of tumors. CyCAP-/- developed larger numbers of tumors than WT animals (p = 0.003, T- Test) as well as overall larger tumor mass (p = 0.016, T-Test). Membranous β-catenin was focally overexpressed in KO mice including proliferative zone of the crypts. Conclusion: CyCAP-/- represent the first described model of spontaneous colonic mucosal hyperplasia. We conclude that CyCAP-deficient mice spontaneously and after challenge with carcinogen develop significantly more colorectal mucosal hyperplasia, an early stage in murine colonic carcinogenesis. Background Colorectal cancer remains a significant cause of morbidity in Western countries [1]. Colorectal carcinoma evolves through multiple pathways (recently reviewed by Jass J. R.)[2]. For many years clinical practice has been focused on early detection and removal of adenomatous polyps by screening colonoscopy is an important strategy for reduc- ing the risk of developing colon cancer [3]. Colorectal ade- noma is considered to be a precursor of about 70% colorectal carcinomas, those that are characterized by chromosomal instability and are microsatellite stable. It appears that as many as 20% of colorectal carcinomas may originate by serrated neoplasia pathway [2]. It has become apparent that clinical management of lesions tra- ditionally diagnosed as "hyperplastic polyps" and gener- ally considered as benign lesions with no malignant potential, may need to change because of the malignant potential associated with some types of serrated polyps including so-called "traditional serrated adenoma" and "sessile serrated adenoma" [1,4-6]. Hyperplasia of the human colon is found in several forms including focal mucosal hyperplasia in hyperplastic polyp, the thickening of the mucosa surrounding colon carcinoma or adenoma, which is termed "transitional mucosa", and regenerative hyperplasia, which may occur in a variety of inflammatory conditions. All of these lesions are considered to be benign, harmless lesions, with no proven premalignant potential [7-9]. Sessile ser- rated polyp is a newly described type of serrated polyp, now recognized as a main actor in a so-called "serrated pathway" of colon carcinogenesis and it shares many fea- tures with the common hyperplastic polyp [5,10,11]. Therefore in humans, two types of colonic serrated mucosal hyperplasia can be distinguished; non-preneo- plastic and preneoplastic. Most forms of mucosal thicken- ing of the colon are due to reactive epithelial hyperplasia and do not lead to malignancy, which is in contrast to mice in which mucosal hyperplasia develops as the first change and also in parallel with colonic epithelial tumors after the treatment with carcinogens [12]. The above observations in humans are in agreement with the notion that not all hyperplastic agents have tumor- promoting activity [13]. For instance, TGF- alpha is a potent in vivo epithelial mitogen which promotes dra- matic hyperplasia in the colon, but does not lead to any alteration in colonic tissue architecture or colonic tumors [14]. TGF- alpha was also found to be absent in ACF in rats and there was reduced amounts of TGF- alpha expres- sion in the upper part of the aberrant crypts compared with the surrounding normal crypts [15]. Although the absence of TGF-alpha was unexpected, it was in accord- ance with observations from recent in vitro studies which demonstrated that the presence of TGF-alpha in the top of the colonic crypt serves to inhibit growth of differentiated colonic epithelial cells [16,17]. In humans, lower levels of TGF-alpha are present in the distal part of the colon, which is the most common site of tumor formation [18]. Additionally, non-preneoplastic secondary mucosal hyperplasia as a reaction to a colonic tumor, so-called "transitional mucosa", possibly develops due to tumoral secretion of IL-15 [19]. Despite these findings, it has been established that thick- ened and serrated colonic mucosa at least in the form of sessile serrated adenoma (synonymously referred to as "atypical hyperplasia"), represents a morphologic entity of the serrated neoplasia pathway [2,20]. The discovery of different subtypes of serrated polyps enabled morpho- logic separation of the harmless hyperplastic lesions from those that are likely to be precancerous [4,6]. It is possible that precancerous serrated polyps of the colon represent a human homologue of the murine pre-neoplastic hyper- plasia induced by carcinogens since these represent the only form of "hyperplasia" of human colonic mucosa that has been biologically linked to colorectal carcinoma [2]. The tumor-associated antigen 90 K (TAA90K) [21,22], also known as Mac-2-binding protein or 90 K, is a secreted 90–100 kDa glycoprotein widely expressed in human flu- ids [23], tumor derived cell lines including those with epi- thelial differentiation [24-28] and elevated in the serum of cancer patients [Iacobelli et al., 1993; Natoli et al., 1993; Iacobelli et al., 1994; Greco et al., 2004] as well as sufferers from other nonmalignant diseases such as AIDS [29,30]. It is a member of the scavenger-receptor cysteine-rich domain superfamily implicated in development and reg- ulation of the immune system [31]. On the other hand, its aberrant expression by epithelial neoplastic cells has also Page 2 of 11 (page number not for citation purposes)