Endogenous peroxidase activity in the sections was quenched by immersion in 3% hydrogen peroxide (cat. neoplastic endocrine tissues, the VT7 clone exhibited immunoreactivity with Quinestrol all neuroendocrine cell types. In conclusion, all seven antibodies detected TIMP-1 protein in various normal and neoplastic FFPE tissues, but one clone, VT7, was superior for IHC staining of TIMP-1 in FFPE tissue sections when using HIER. Keywords: tissue inhibitor of metalloproteinase-1, VT7, immunohistochemistry, monoclonal antibodies, neuroendocrine tissue Tissue inhibitor of metalloproteinase-1 (TIMP-1) is usually a 28.5-kDa glycoprotein consisting of 184 amino acids in the mature protein and is the most extensively studied of the four TIMP family proteins (TIMP-1, ?2, ?3, and ?4) characterized so far (Welgus et al. 1979; Stricklin and Welgus 1983; Welgus and Stricklin 1983; Carmichael et al. 1986; Gomez et al. 1997). TIMP-1 was originally named for the ability to inhibit the activity of the matrix metalloproteinases (MMPs), which is a family of Zn2+- dependent endopeptidases (consisting so far of 24 members) Quinestrol (Mook et al. 2004) that are capable of degrading most, if not all, components of the extracellular matrix (Curran and Murray 1999). However, TIMP-1 also exhibits several other biological functions including stimulation of proliferation in various cell types (Brew et al. 2000; Fassina et al. 2000; Lafleur et al. 2003) and inhibition of apoptosis (Guedez et al. 1998; Li et al. 1999; Murphy et al. 2002; Lambert et al. 2003; Liu et al. 2003). TIMP-1 is present in a wide range of normal and pathological tissues as well as in body fluids (Welgus and Stricklin 1983; Cawston et al. 1986; Tomita and Iwata 1996,1997,1999; Tomita 1997a,b; Isisag et al. 2003; Holten-Andersen et al. 2005; Quinestrol Liu et al. 2005). However, it is particularly the involvement of TIMP-1 in various cancers that has made this molecule the subject of many studies. Although early studies have shown TIMP-1 to have anti-tumor or anti-metastatic effects (Schultz et al. 1988; Khokha et al. 1989; Alexander and Werb 1992), more recent reports indicate a dual function with positive correlation between increased TIMP-1 tumor tissue levels and poor outcome in colorectal, breast, and non-small-cell lung cancer (Fong et al. 1996; Murashige et al. 1996; Ree et al. 1997; Wurtz et al. 2005). Our own studies have shown that plasma levels of TIMP-1 also carry the potential as a marker for colorectal cancer prognosis (Holten-Andersen et al. 2000). In addition, we have found that plasma TIMP-1 measurements can be used for the early detection of colorectal cancer (Holten-Andersen et al. 1999,2002). By immunohistochemistry (IHC), TIMP-1 localization studies in various neoplastic tissues have similarly exhibited TIMP-1 as a potential tumor marker for different cancers, e.g., colorectal cancer (Holten-Andersen et al. 2005) and breast cancer (Jones et al. 1999). Common to these cancers is usually that TIMP-1 is usually primarily Quinestrol located in the stromal compartment of the tumors. In contrast, in various human neuroendocrine cancers, TIMP-1 protein is usually localized exclusively to the tumor cells, e.g., in islet cell tumors (Tomita and Iwata 1997), medullary thyroid carcinoma (MTC) (Tomita 1997b), parathyroid carcinoma (Tomita and Iwata 1999), and Merkel cell carcinoma (Massi et al. 2003). IHC for detection TSPAN11 of various tumor markers in neoplastic formalin-fixed, paraffin-embedded (FFPE) tissue sections have often demonstrated very conflicting interlaboratory results. Localization studies of.