title: Two initiation sites of early detection of colon cancer, revealed by             localization of pERK1/2 in the nuclei or in aggregates at the perinuclear region             of tumor cells.
abstract: We have used human specimens and antibodies to pERK1/2 to detect early development             of colon cancer, using indirect immunocytochemistry. Two distinct sites were stained;             one at the tip of the colon villi and the other in the stromal tissue, associated             with the colon tissue. These foci represent early stages of colon cancer initiation,             as established by enhanced KRAS, and lack of p53 staining. It should be noted,             however, that the enhanced KRAS coincides with the initiation of tumor growth             revealed by pERK1/2 only in the tip of the colon villi but not in the stromal             initiation site of the colon tumors. Interestingly, foci of pERK1/2 staining were             also detected within 50% of stromal tissue and tips of colon villi, that were             classified as normal tissues, distal from the malignant one according to general             morphology. The staining of pERK1/2 at the stromal foci of this apparently non-malignant             tissue appeared as aggregates at the perinuclear region, while at the colon epithelium,             it appeared at the cell nuclei. At low-grade of colon cancer, that was still free             of induced mutated p53, staining of pERK1/2 was prominent at the cell nuclei both             at the stroma tissue and the tip of the colon villi. In intermediate stage, that             exhibited a significant p53 staining, only a fraction of p53-free tumor cells             was labeled with pERK1/2 antibody, while in high-grade tumors, all cells of tumors             were labeled with antibodies to p53, but not with pERK1/2. We also found that             the cytoplasm of low-grade tumors was positive for epiregulin, while this labeling             decreased in high-grade tumors. Interestingly, we found that the tumors initiating             from the stroma demonstrated poor structural differentiation, while the tumors             initiating from the epithelial cells of the colon demonstrated high structural             differentiation. It is concluded that pERK1/2 is a sensitive early marker of colon             cancer, which disappears at later stages of cancer development. Moreover, pERK1/2             staining can distinguish between tumor cells originated from the tip of the colon             villi and those originated in the stroma, associated with the colon tissue, and             thus can assist in selecting the appropriate therapy.
authors: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel. abraham.amsterdam@weizmann.ac.il
authors: Abraham
authors: A
authors: Amsterdam
authors: Elias
authors: E
authors: Shezen
authors: Calanit
authors: C
authors: Raanan
authors: Letizia
authors: L
authors: Schreiber
authors: Yasmin
authors: Y
authors: Slilat
authors: Yakov
authors: Y
authors: Fabrikant
authors: Ehud
authors: E
authors: Melzer
authors: Rony
authors: R
authors: Seger
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002467:Cell Nucleus / Q000201:enzymology* / Q000473:pathology; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism* / Q000473:pathology; D055088:Early Detection of Cancer / Q000379:methods; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009367:Neoplasm Staging / Q000379:methods; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins