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The adenoma‑carcinoma sequence, the sequential mutation and deletion of various genes by which colorectal cancer progresses, is a well‑established and accepted concept of colorectal cancer carcinogenesis. Proteins of the polycomb repressive complex 2 (PRC2) function as transcriptional repressors by trimethylating histone H3 at lysine 27; the activity of this complex is essential for cell proliferation and differentiation. The histone methyltransferase enhancer of zeste homolog 2 (EZH2), an essential component of PRC2, is associated with the transcriptional repression of tumor suppressor genes. EZH2 expression has previously been reported to increase with the progression of pancreatic intraductal papillary mucinous neoplasm. Thus, we hypothesized that EZH2 expression also increases during the adenoma‑carcinoma sequence of colorectal cancer. The present study investigated changes in EZH2 expression during the colorectal adenoma‑carcinoma sequence. A total of 47 patients with colorectal adenoma, 20 patients with carcinoma in adenoma and 43 patients with colorectal carcinoma who underwent surgical or endoscopic resection were enrolled in this study. Non‑cancerous tissue from the clinical specimens was also examined. The association between EZH2 expression, pathology and expression of tumor suppressor genes during colorectal carcinogenesis were analyzed. Each specimen was immunohistochemically stained for EZH2, proliferation marker protein Ki‑67 (Ki‑67), cyclin‑dependent kinase inhibitor (CDKN) 1A (p21), CDKN1B (p27) and CDKN2A (p16). Total RNA was extracted from formalin‑fixed paraffin‑embedded blocks and reverse transcription‑quantitative polymerase chain reaction analysis of these genes was performed. Ki‑67 and EZH2 expression scores increased significantly during the progression of normal mucosa to adenoma and carcinoma (P=0.009), and EZH2 expression score was positively associated with Ki‑67 expression score (P=0.02). Conversely, p21 mRNA and protein expression decreased significantly, whereas expression of p27 and p16 did not change significantly. During the carcinogenesis sequence from normal mucosa to adenoma and carcinoma, EZH2 expression increased and p21 expression decreased significantly. EZH2 may therefore contribute to the development of colorectal cancer from adenoma via suppression of p21. [ABSTRACT FROM AUTHOR]

Mechanisms underlying tumor progression remain a main problem in the diagnosis and treatment of patients with tumors. The present study compared the expression of full-length neurokinin-1 receptors (fl-NK-1R) and truncated neurokinin-1 receptors (tr-NK-1R) in adenoma and carcinoma from patients with colorectal carcinoma, to explore their possible contributions in adenoma-carcinoma progression. Samples were collected immediately following colorectal carcinoma surgery. Using reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining, the relative mRNA and protein levels of tr-NK-1R and fl-NK-1R were compared in adenoma and carcinoma. tr-NK-1R mRNA was significantly upregulated (1.7 fold; P=0.026) in carcinoma tissues compared with adenoma tissues, while the fl-NK-1R transcription level showed no difference (P=0.438). No significant change was observed in the fl-NK-1R protein level in adenoma, carcinoma and peri-carcinoma tissues (P=0.244). However, total neurokinin-1 receptor (NK-1R) protein levels in adenoma and carcinoma tissues were significantly increased compared to peri-carcinoma tissue (P=0.026 and P=0.007, respectively). The outcomes suggested that the increase in total NK-1R protein in adenoma and carcinoma tissues is the result of the increase in tr-NK-1R levels. The present findings indicate that tr-NK-1R serves an important role in colorectal adenoma progression, with a possible role in adenoma-carcinoma progression. Thus, tr-NK-1R may be used as a marker for diagnosing and treating patients with colorectal adenomas. [ABSTRACT FROM AUTHOR]

Mechanisms underlying tumor progression remain a main problem in the diagnosis and treatment of patients with tumors. The present study compared the expression of full-length neurokinin-1 receptors (fl-NK-1R) and truncated neurokinin-1 receptors (tr-NK-1R) in adenoma and carcinoma from patients with colorectal carcinoma, to explore their possible contributions in adenoma-carcinoma progression. Samples were collected immediately following colorectal carcinoma surgery. Using reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining, the relative mRNA and protein levels of tr-NK-1R and fl-NK-1R were compared in adenoma and carcinoma. tr-NK-1R mRNA was significantly upregulated (1.7 fold; P=0.026) in carcinoma tissues compared with adenoma tissues, while the fl-NK-1R transcription level showed no difference (P=0.438). No significant change was observed in the fl-NK-1R protein level in adenoma, carcinoma and peri-carcinoma tissues (P=0.244). However, total neurokinin-1 receptor (NK-1R) protein levels in adenoma and carcinoma tissues were significantly increased compared to peri-carcinoma tissue (P=0.026 and P=0.007, respectively). The outcomes suggested that the increase in total NK-1R protein in adenoma and carcinoma tissues is the result of the increase in tr-NK-1R levels. The present findings indicate that tr-NK-1R serves an important role in colorectal adenoma progression, with a possible role in adenoma-carcinoma progression. Thus, tr-NK-1R may be used as a marker for diagnosing and treating patients with colorectal adenomas.