Abstract. annexin a1 (anxa1) is a calcium-dependent phospholipid-linked protein, involved in anti-inflammatory effects, regulation of cellular differentiation, proliferation and apoptosis. In the present study, we investigated the expression of anxa1 in gastric and colon cancer, and analyzed the relationship between ANXA1 expression and clinicopathological factors. anxa1 mrna expression in gastric and colon cancer tissues was not significantly changed compared to that in normal tissues. When anxa1 protein expression was evaluated by immunohistochemical staining, ANXA1 expression was observed in 76 of 135 cases of gastric cancer (56.3%), and correlations were found between ANXA1 expression and depth of wall invasion (P<0.001), lymphatic invasion (P=0.023), venous invasion (P=0.002), lymph node metastasis (P=0.001) and UICC stage (P<0.001). Disease-specific survival rate was significantly lower in cases with ANXA1 expression compared to that in cases without (P=0.0053). In colon cancer, ANXA1 expression was detected in 61 of 210 cases (29.0%) and correlations were found with gender (P=0.038), lymphatic invasion (P=0.011), venous invasion (P=0.023), lymph node metastasis (P=0.042) and UICC stage (P=0.041). The disease-specific survival rate tended to be lower in cases with ANXA1 expression, although the differences were not statistically significant (P=0.6984). Our results indicate that up-regulated ANXA1 expression is involved in cancer invasion and lymph node metastasis. Furthermore, high levels of anxa1 expression were implicated in poor prognosis of patients. ANXA1 may be applicable as a prognostic biomarker in gastric and colon cancer, and a potential target for treatment.

Ubiquitin-like with PHD and ring-finger domain 1 (UHRF1) binds to methylated promoters of a number of tumor-suppressor genes, including p16INK4A and p14ARF, by forming complexes with DNA methyltransferases and HDAC1, resulting in the induction of carcinogenesis. Altered UHRF1 expression has been demonstrated in various types of cancers. Previous reports indicate that UHRF1 expression is regulated by E2F-1 expression. We investigated UHRF1 expression using immunohistochemical staining in 231 colorectal cancer and 40 adenoma specimens, analyzed the relationship between UHRF1 expression and clinicopathological findings and the association between UHRF1 and E2F-1 expression. To better understand the biological function of UHRF1 in colorectal cancer, knockdown of UHRF1 expression was performed using siRNA methods. High UHRF1 expression was observed in 152 of 231 (65.8%) colorectal cancer patients, and was detected in 35 of 40 adenoma specimens samples (87.5%). UHRF1 staining was detected in the nucleus of cancer cells, while it was not detected in colonic normal mucosa. High UHRF1 expression was significantly observed in right compared with left hemicolon cancer (p=0.008). Moreover, high UHRF1 expression tended to be associated with depth of invasion (p=0.051). UHRF1 expression was significantly associated with E2F-1 expression (p<0.0001). Knockdown of UHRF1 expression suppressed cellular growth in colon cancer cell lines, HCT116 and SW620. In conclusion, we demonstrated that UHRF1 expression was upregulated in approximately two-thirds of colorectal cancer specimens and was particularly expressed in right compared with left hemicolon cancer. Moreover, knockdown of UHRF1 expression induced growth inhibition in colon cancer cell lines. UHRF1 may be involved in cellular proliferation and molecular pathogenesis of colorectal cancer in the right hemicolon.

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Abstract.Previous studies have shown that the L-type amino acid transporter 1 (LAT1) is highly expressed in many types of cancer. Upregulated LAT1 expression is considered to be associated with cancer cell proliferation. In the present study, we investigated LAT1 expression in 210 patients with colorectal cancer (CRC) and 40 patients with colonic adenoma using an immunohistochemical method, and analyzed the associations between LAT1 expression and clinicopathological factors and prognosis. The biological significance of LAT1 was also examined under conditions with sub-normal amounts of essential amino acids using colon cancer cell lines. High expression of LAT1 was observed in 152 of 210 CRC patients (72.4%) and 12 of 40 patients with colonic adenoma (30%), and this difference in the frequency of LAT1 expression between CRC and adenoma was significant (P<0.001). High expression of LAT1 was associated with venous invasion (P=0.027). The restriction of amino acids suppressed cell proliferation in CRC cells with higher LAT1 expression, while cellular proliferation was not suppressed in the cells expressing lower levels of LAT1. Mammalian target of rapamycin (mTOR) expression was also downregulated under restricted availability of amino acids, suggesting that the restriction of amino acids induced an antitumor effect through inhibition of the LAT1/mTOR pathway. In summary, the present study demonstrated that LAT1 expression is frequently upregulated in CRC and is associated with cancer cell proliferation via the mTOR pathway.

Pancreatic metastatic tumors from thyroid carcinoma are extremely rare. We report a case of an 80-year-old female with a pancreatic metastatic tumor derived from papillary thyroid carcinoma which was initially resected 158 months prior to detection of the metastatic pancreatic tumor. The patient has encountered cervical lymph-node metastasis on three occasions following the initial operation. Metastatic pancreatic lesions and cervical lymph nodes were first detected using 18-fluorodeoxyglucose positron-emission tomography/computed tomography, and she was preoperatively diagnosed using endoscopic ultrasound-guided fine-needle aspiration biopsy. A coin lesion, 10 mm in size, was detected in the left lung by chest computed tomography with no abnormal uptake in 18-fluorodeoxyglucose positron-emission tomography/computed tomography. Distal pancreatectomy and cervical lymph-node dissection were performed. Adjuvant chemotherapy with weekly paclitaxel was administered because anaplastic transformation had been detected in one of the cervical lymph nodes. The patient eventually died from multiple lung metastases 11 months after removing the metastatic pancreatic lesion. We reported a rare case of a pancreatic metastatic tumor from thyroid carcinoma, and found that 18-fluorodeoxyglucose positron-emission tomography/computed tomography and endoscopic ultrasound-guided fine-needle aspiration biopsy are useful for preoperatively diagnosing tumors.