Role of COX-2 in carcinogenesis of colorectal cancer and its relationship with tumor biological characteristics and patients' prognosis

AIM: Recent clinical epidemiological studies havedemonstrated the preventive effect of non-steroidal anti-inflammatory drugs (NSAIDs) against colorectal cancer.The underlying mechanism might be the inhibition of rate-limiting enzyme cyclooxygenase-2 (COX-2) in metabolismof arachidonic acid. The role of COX-2 in carcinogenesisof colorectal cancer and its relationship with tumorbiological characteristics and patients′ prognosis stillremain unclear. This study was to investigate the role ofCOX-2 expression in carcinogenesis of colorectal cancerand its relationship with tumor biological characteristicsand patients′ prognosis.METHODS: A total of 139 colorectal cancers and 19adenomas surgically treated in School of Oncology, PekingUniversity, from January 1993 to September 2001 wereretrospectively studied. COX-2 expression was detected withtissue microarray (TMA) and immunohistochemistry (IHC)procedure. The association between COX-2 expression andclinicopathological features and its influence on patients′prognosis were studied.RESULTS: COX-2 expression was strong in colorectal cancer,moderate in adenoma and weak in normal mucosa, whichdemonstrated statistically significant difference (x2=46.997,P＜0.001). COX-2 expression had no association withclinicopathological features such as gross type,differentiation, invasion depth, vessel emboli and TNMstaging. Cox proportional hazards modeling analysis and Logrank test revealed no prognostic role of COX-2 expressionin colorectal cancer patients.CONCLUSION: COX-2 may play an important role in theearly stage of carcinogenesis, and its expression in colorectalcancer is not associated with clinicopathological features and patients′ prognosis.

Clinical significance of matrix metalloproteinase-9 expression in esophageal squamous cell carcinoma

AIM: To evaluate the expression of matrix metalloproteinase-9 (MMP-9) and its clinical significance in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of MMP-9 in 208 cases of ESCC was detected by immunohistochemistry (IHC) and its clinical significance in ESCC especially the relationship with the clinicopathological parameters was analyzed. RESULTS: The percentage of positive cases for MMP-9 detected by IHC was 49.0%. MMP-9 was mainly expressed in the cytoplasm of cancer cells especially in the invasive front. Only weak expression was detected in the stromal cells and no expression in non-cancerous mucosa. The expression of MMP-9 was positively correlated with poorer differentiation (P= 0.001<0.01), existence of vessel permeation (P= 0.027<0.05) and lymph node metastasis (P=0.027<0.05). CONCLUSION: The expression of MMP-9 correlates with the cancer cell differentiation, vessel permeation and lymph node metastasis. It may be a novel biomarker for the diagnosis and treatment of ESCC.

COX-2 expression and tumor angiogenesis in colorectal cancer

AIM: Cyclooxygenase-2 (COX-2) is one of the rate-limiting enzymes in metabolism of arachidonic acid, and COX-2 inhibitors demonstrate preventive effects on cancer,especially on colorectal cancer. The underlying mechanism remains unclear. The aim of this study was to illustrate the relationship between angiogenesis and COX-2 in carcinogenesis of colorectal cancer.METHODS: One hundred and seventy patients with colorectal cancer were enrolled in our study from January 1993 to September 2001 in School of Oncology, PekingUniversity. COX-2 and VEGF expression were detected with the immunohistochemistry (IHC) technique. IHC assays were carried out with the aid of tissue microarray (TMA)procedure. Specimens from 35 of these patients were examined with reverse transcriptase PCR (RT-PCR).RESULTS: COX-2 and VEGF expressions were stronger in colorectal cancer than those in the corresponding normal tissues, at both protein and mRNA levels. One hundred patients were eligible for analysis after IHC assay of COX-2 and VEGF. The positive rate of VEGF was much higher in COX-2 positive group (47/85) than in COX-2 negative group (x^2 = 4.181, P= 0.041). The result was further verified by the result of RT-PCR (x^2 = 8.517, P = 0.003). Correlation coefficient was 0.409 after Spearman correlation analysis (P=0.015).CONCLUSION: COX-2 may be involved in the course of tumor angiogenesis of colorectal cancer and acts through VEGF.

Angiography for diagnosis and treatment of colorectal cancer

AIM: To evaluate the role of preoperative angiography inthe diagnosis and treatment of colorectal cancer.METHODS: The authors performed selective arterialcannulation by Seldinger's method in 47 patients to locatethe primary cancer and to diagnose metastasis to the liver.Each patient was then given intra-arterial regionalchemotherapy, and received 5-fluorouracil (5-Fu, 1 000 mg),mitomycin C (MMC, 20 mg), and cisplatinum (CDDP, 80 mg).RESULTS: The location and shape of each tumor wereobserved, including metastatic tumors in the liver, in 42 ofthe 47 (89.4 %) patients. The site of the primary tumor wasdifficult to identify in 5 cases because the patients had arecurrence of cancer. Arterial chemotherapy was performedsuccessfully in all patients. The authors recorded no partialor significant morbidity resulted from angiography. The onlyincident was bleeding from the artery puncture site in onepatient, which was successfully stopped by generalmedication.CONCLUSION: Preoperative selective arterial angiographycan help the diagnosis and locate primary tumors and todetect liver metastasis. At the same time, regional arterialchemotherapy can be an important form of preoperativetherapy.

Oncologic outcomes of primary and post-irradiated early stage rectal cancer: A retrospective cohort study

AIM: To evaluate the oncologic outcomes of primary and post-irradiated early stage rectal cancer and the effectiveness of adjuvant chemotherapy for rectal cancer patients. METHODS: Eighty-four patients with stage Ⅰ rectal cancer after radical surgery were studied retrospectively and divided into ypstage Ⅰ group (n = 45) and pstage Ⅰ group (n = 39), according to their preoperative radiation, and compared by univariate and multivariate analysis. RESULTS: The median follow-up time of patients was 70 mo. No significant difference was observed in diseaseprogression between the two groups. The 5-year disease-free survival rate was 84.4% and 92.3%, respectively (P = 0.327) and the 5-year overall survival rate was 88.9% and 92.3%, respectively, for the two groups (P = 0.692). The disease progression was not significantly associated with the pretreatment clinical stage in ypstage Ⅰ group. The 5-year disease progression rate was 10.5% and 19.2%, respectively, for the patients who received adjuvant chemotherapy and for those who rejected chemotherapy in the ypstage Ⅰ group (P = 0.681). CONCLUSION: The oncologic outcomes of primary and post-irradiated early stage rectal cancer are similar. Patients with ypstage Ⅰ rectal cancer may slightly benefit from adjuvant chemotherapy.

A Case Report on Paraneoplastic Pemphigus Associated Colonic Carcinoma

Paraneoplastic pemphigus mucocutaneous syndrome, has （PNP）, an acantholytic a universal association with malignancy and a poor prognosis, The clinical picture is characterized by painful mucosal erosions, ulcerations, and polymorphous skin lesions that progress to blistering eruptions on the trunk and extremities. In the reviews of all PNP, hematologic malignancies such as non-Hodgkin＇s lymphoma, chronic lymphocytic leukemia, and Castleman＇s disease account for the most part; nonhematologic malignancies are very seldom especially adenocarciuoma of colon, These will be illustrated in the following paper on the basis of a case report of a patient with colonic adenocarcinoma who presented with PNP.