[Show abstract][Hide abstract] ABSTRACT: The serrated colorectal carcinoma (CRC) as proposed to arise from serrated adenoma (SA) is characterized by up-regulation of HIF1α, suppression of PTCH or EphB2, loss of DNA repair proteins and BRAF mutation. The aim of this study was to evaluate alterations of these candidates involved in the serrated pathway in colorectal polyps.
We analyzed immunoreactivity of these proteins, methylation of PTCH and EphB2, and mutation of BRAF and Kras in sessile SAs (SSAs; n = 32), traditional SAs (TSAs; n = 28), hyperplastic polyps (HPs; n = 24) and conventional adenomas (ADs; n = 21).
Increase of nuclear HIF1α expression was more frequent in SA than HP, but less frequent in SA than AD (P < 0.001). Increase of PTCH expression was not found in SSA or HP, but was evident in about half of TSA and all AD (P < 0.001). Decrease of EphB2 expression was more prominent in SA than HP or AD (P ≤ 0.005). Loss of hMLH1 and MGMT expression were most frequent in SSA (P < 0.001). Loss of hMSH2 showed more pronounced in SA and HP than AD (P ≤ 0.004). Methylations of PTCH and EphB2 were rare in all categories. BRAF mutation harbored frequently in SA, but not AD; only AD harbored Kras mutation.
This work provides evidence of similarity of HIF1α, EphB2 or DNA repair proteins expression and BRAF mutation in serrated CRCs and their precursors, especially SSA, compared to AD and HP.
Journal of Gastroenterology and Hepatology 02/2014; · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To clarify differences in mucin phenotype, proliferative activity and oncogenetic alteration among subtypes of colorectal laterally spreading tumor (LST).
LSTs, defined as superficial elevated lesions greater than 10 mm in diameter with a low vertical axis, were macroscopically classified into two subtypes: (1) a granular type (Gr-LST) composed of superficially spreading aggregates of nodules forming a flat-based lesion with a granulonodular and uneven surface; and (2) a non-granular type (NGr-LST) with a flat smooth surface and an absence of granulonodular formation. A total of 69 LSTs, comprising 36 Gr-LSTs and 33 NGr-LSTs, were immunohistochemically stained with MUC2, MUC5AC, MUC6, CD10 (markers of gastrointestinal cell lineage), p53, β-catenin and Ki-67 antibodies, and examined for alteration in exon 1 of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and exon 15 of v-raf murine sarcoma viral oncogene homologue B1 (BRAF) by polymerase chain reaction followed by direct sequencing.
Histologically, 15 Gr-LST samples were adenomas with low-grade dysplasia (LGD), 12 were high-grade dysplasia (HGD) and 9 were adenocarcinomas invading the submucosa (INV), while 12 NGr-LSTs demonstrated LGD, 14 HGD and 7 INV. In the proximal colon, MUC5AC expression was significantly higher in the Gr-type than the NGr-type. MUC6 was expressed only in NGr-LST. MUC2 or CD10 did not differ. P53 expression demonstrated a significant stepwise increment in progression through LGD-HGD-INV with both types of LST. Nuclear β-catenin expression was significantly higher in the NGr-type. Ki-67 expression was significantly higher in the Gr-type in the lower one third zone of the tumor. In proximal, but not distal colon tumors, the incidence of KRAS provided mutation was significantly higher in the Gr-type harboring a specific mutational pattern (G12V). BRAF mutations (V600E) were detected only in two Gr-LSTs.
The two subtypes of LST, especially in the proximal colon, have differing phenotypes of gastrointestinal cell lineage, proliferation and activation of Wnt/β-catenin or RAS/RAF/extracellular signal-regulated kinase signaling.
World Journal of Gastroenterology 10/2012; 18(39):5551-9. · 2.43 Impact Factor