Positive Cyclooxygenase-2 Expression Research Articles

The Expression of Cyclooxygenase-2 in Cervical Intraepithelial Neoplasia and Cervical Cancer.

Aim To examine the relationship between tumor differentiation, parametrial, and lymphovascular invasion, as well as the differential expression pattern of cyclooxygenase-2 (COX-2) in cervical intraepithelial neoplasia and various forms of cervical cancer. Methods Histologically diagnosed cases of in-situ and malignant lesions of the cervix were included in the study. Two sections were cut from paraffin blocks. One section was stained with Haematoxylin and Eosin (H&E) for morphologic diagnosis, and the other sections were subjected to COX-2 immunohistochemical staining. Cases of colon carcinoma were taken as positive controls. Cytoplasmic and membrane staining of tumor cells were considered as positive staining, and grading was done. Results Out of the 62 patients, 40 cases (64.5%) showed positive expression of COX-2 in squamous cell carcinoma when compared to in-situ cervical intraepithelial neoplasia and adenocarcinoma. The results were statistically significant, with a p-value of 0.003. Conclusion COX-2 expression is directly proportional to the level of grading of the tumor. The higher the grading, the higher the expression of COX-2. Selective COX-2 inhibitors increase the efficacy of chemotherapy or radiotherapy.

The clinicopathological and immunohistochemical features of breast carcinomas with signet-ring-cell differentiation

BackgroundThis study investigated the clinicopathological features, immunophenotypic characteristics and differential diagnosis of primary breast carcinomas with signet ring cell differentiation, as well as differences in the traits of signet ring-like cell mucin.MethodsA total of five cases of primary breast cancer diagnosed with signet ring cell differentiation and treated at The First People’s Hospital of Jingmen from January 2016 to December 2021 were collected. HE, immunohistochemical staining, and AB-PAS staining were used for the analysis.ResultsAlthough we strictly selected all the primary breast cancer cases with signet ring cell differentiation, there were differences in the arrangement of the cells and the grading of nuclei. Our immunohistochemical results showed that the ER was consistently strongly positive, and the PR expression was not consistent, while all the cases of HER2 were negative. CK7 was negative in one case, and CK20 and CK5/6 were not expressed in all the cases. The mucin MUC1 was positive and showed two patterns. MUC2 was strongly positive in all the cases. All the cases were negative for CDX2, SATB2, PAX8, TTF-1, and Napsin A, while the positive expression of COX2, Villin, and WT-1 was not constant. One case expressed neuroendocrine markers. The expression level of Ki67 was between 10 and 30%. AB (pH 2.5)-PAS staining revealed that the intracellular mucus contained more cells with neutral mucus, while the extracellular mucus was mainly acidic.ConclusionWe found that histological morphology, cell morphology, and nuclear grading differentiate among different cases. The immunohistochemical characteristics of primary breast cancers diagnosed with signet ring cell differentiation are helpful for identification. The differences in the expression patterns of mucins may be related to unfavorable clinicopathological factors, but their usefulness as a prognostic marker remains to be further understood. The heterogeneity of cell mucus, the differentiation of tumor cells, and the phenotypic changes of tumors also need further study.

Colonic mucosal eosinophilia and immunohistochemical expression of COX-2 and NF-kB in patients with irritable bowel syndrome.

There is growing evidence that eosinophilic infiltration can release mediators which are harmful to the intestinal epithelium in patients with irritable bowel syndrome (IBS). Although cyclooxygenase 2 (COX-2) and nuclear factor-kappa beta (NF-kB) expression had been previously reported to increase in many inflammatory conditions, there is a paucity in data investigating their expressions in IBS. Our aim was to evaluate colonic mucosal eosinophilia and immunohistochemical expression of COX-2 and NF-kB in patients with irritable bowel syndrome. A total of 80 patients who met the inclusion criteria of IBS based on Rome IV symptoms questionnaire were subjected to abdominal ultrasound, laboratory investigations, serum immunoglobulin E (IgE) level assessment and colonoscopic examination. Immunohistochemistry was performed to detect COX-2 and NF-kB expression in colonic biopsies obtained from IBS patients. Histopathological examination showed that 60 colonic biopsy specimens (75%) showed few mixed inflammatory cells ≤3 cells/ HPF, 12 biopsy specimens (15%) showed eosinophilic infiltration ≥25 eosinophils/HPF and 8 biopsy specimens (10%) showed severe lymphocytic infiltration and aggregation. Colonic eosinophilic infiltrate was significantly higher among patients presented with IBS-D subtype. Serum IgE was significantly higher among patients with colonic eosinophilic infiltrate than the others. In IBS-D patients, colonic mucosa showed positive expression of COX-2 and NF-kB in 52.1% and 81.25% of cases, respectively. Patients with IBS -particularly IBS-D subtype- should undergo colonoscopy and biopsy to exclude underlying inflammatory pathology. Moreover, patients with positive COX-2 and NF-kB need further evaluation and follow-up.

ω-3 and ω-6 Polyunsaturated Fatty Acids Regulate the Proliferation, Invasion and Angiogenesis of Gastric Cancer Through COX/PGE Signaling Pathway.

BackgroundThis study aims to investigate the effects of ω-3, ω-6 polyunsaturated fatty acids (PUFAs), and their middle metabolites prostaglandin (PGE)2 and PGE3 on proliferation, invasion, and angiogenesis formation of gastric cancer cells and to explore associated mechanism.MethodsRT-PCR and ELISA were used to detect the expression of cyclooxygenase (COX)-1 and COX-2 in gastric cancer cell lines. The effect of ω-3, ω-6, PGE2, and PGE3 on the proliferation, invasion, and angiogenesis of gastric cancer cells were measured by cell proliferation, invasion, and angiogenesis assay in vitro. COX-2 small interfering RNA (siRNA) was transfected into gastric cancer cells, and the expression of COX-2 protein was detected by Western blot. COX-2 gene silencing influencing proliferation, invasion, and angiogenesis potential of gastric cancer cells was detected by WST-1, transwell chamber, and angiogenesis assay, respectively.ResultsCOX-2 was only expressed in MKN74 and MKN45 cells. In gastric cancer cell lines with positive COX-2 expression, ω-6 and PGE2 could significantly enhance the proliferation, invasion, and angiogenesis of gastric cancer cells, and after transfection with COX-2 siRNA, the effects of ω-6 and PGE2 on enhancing the proliferation, invasion, and angiogenesis of gastric cancer cells were significantly attenuated; ω-3 and PEG3 could inhibit the proliferation, invasion, and angiogenesis of gastric cancer cells. In gastric cancer cell lines with negative COX-2 expression, ω-6 and PGE2 had no significant effect on the proliferation, invasion, and angiogenesis of gastric cancer; ω-3 and PGE3 could significantly inhibit the proliferation, invasion, and angiogenesis of gastric cancer.Conclusionω-6 PUFAs reinforce the metastatic potential of gastric cancer cells via COX-2/PGE2; ω-3 PUFAs inhibit the metastatic potential of gastric cancer via COX-1/PGE3 signaling axis.

Expression and prognostic significance of cyclin D1 and cyclooxygenase-2 in colorectal carcinoma

Background Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Cyclin D1 (CNND1) and cyclooxygenase-2 (Cox-2) are expressed in a plethora of neoplastic tissues. Aim The present work was conducted to examine the immunohistochemical expression of CNND1 and Cox-2 in colorectal adenocarcinoma, compared with colonic adenoma to evaluate its association with various clinicopathological features. Patients and methods A total of 30 colorectal adenocarcinoma cases, 20 cases of colonic adenoma, and 10 normal colonic mucosal biopsies as controls were studied. Immunohistochemical technique was applied to detect CNND1 and Cox-2 expression and correlate them with clinicopathological findings. Results Both cytoplasmic high CNND1 and nuclear positive Cox-2 expression were significantly increased from normal colonic mucosa (0 and 10%, respectively) to CRC (80 and 83.3%, respectively) passing through colon adenoma (25 and 55%, respectively) (P≤0.001 for both). High CNND1 score was significantly related to lymph node spread and stage (P≤0.001 for both). A statistically significant difference was documented between Cox-2 and grade of differentiation (P=0.017), distant metastasis, and TNM stage (P=0.033, 0.003, respectively). Conclusion The present work suggests the oncogenic role of CNND1 and Cox-2 in CRC. Furthermore, overexpressions of CNND1 and Cox-2 are associated with poor prognostic factors, implicating their potentially prognostic role in CRC.

Cyclooxygenase-2 expression in colorectal carcinoma, adenomatous polyps and non-tumour bearing margins of resection tissues in a cohort of black Africans.

BackgroundEmerging data suggest a negative role of cyclooxygenase-2 (COX-2) in colorectal carcinomas (CRC). Investigating this in developing communities such as ours helps to contribute to existing understanding of these lesions.Methods and findingsFormalin-fixed paraffin-embedded CRC colectomy tissues and their corresponding non-tumour margins of resected tissues were sectioned and stained with COX-2 antibody. Adenomatous polyp tissues from non-cancer bearing individuals were similarly processed for comparison. COX-2 expression was scored for percentage (< 5% = 0; 6%-25% = 1; 26%-50% = 2; 51%-75% = 3; 76%-100% = 4) and intensity (no staining = 0; yellow = 2; yellowish-brown = 3, brown = 4). Total immunoscore (percentage + intensity score) ≥ 2 was regarded as positive COX-2 expression. Outcome was statistically evaluated with clinicopathological data to determine COX-2 expression-associated and predictor variables. Ninety-five CRC cases and 27 matched non-tumour tissues as well as 31 adenomatous polyps met the inclusion criteria. Individuals with CRC had a mean age of 56.1 ± 12.6 years while those with adenomatous polyps had a median age of 65 years (range 43–88). COX-2 was differentially overexpressed in CRCs (69/95; 72.6%) and in adenomatous polyps (17/31; 54.8%) than in non-tumour tissues 5/27 (18.5%); p < 0.001). The difference in COX-2 expression between CRC and polyps was non-significant (p > 0.065). Tumour grade, advanced pT-stage, tumour-infiltrating lymphocytes, and dirty necrosis were also significantly associated with COX-2 expression (p < 0.035; 0.043, 0.035 and 0.004, respectively). Only dirty necrosis and Crohns-like lymphocytic aggregates predicted COX-2 expression (p < 0.05).ConclusionThis study showed a progressive increase in COX-2 expression from normal to adenomatous polyp and CRC tissues, this being associated with poorer prognostic indicators. Although COX-2 appears early in CRC, it may play a secondary role in promoting tumour growth and invasiveness.

Expression of cyclooxygenase-2 in imprint smears of endometrial carcinoma.

Worldwide, endometrial carcinoma is one of the most frequently diagnosed cancers among women and a considerable cause of death. The aims of this study were to determine the expression of cyclooxygenase-2 (COX-2) in endometrial adenocarcinoma in imprint smears as an alternative technique and to correlate the results with clinicopathologic parameters of primary untreated endometrial cancer patients. One hundred twenty-six patients with endometrial carcinoma were evaluated with samples freshly resected after a total abdominal hysterectomy during a 29-month period. The cytologic imprint smears were obtained by touching the cut surface of cancer tissues and the expression of COX-2 was assessed by immunocytochemistry. The positive expression of COX-2 in malignant cells, was accompanied by morphologic features of more aggressiveness (pathogenetic type II, advanced clinical stage, mainly high grade, deep myometrial involvement >1/2) tumors and the affected from the disease lymph nodes cases showed higher positivity (41.2%) than the non-affected (13.4%). Immunocytochemical findings from COX-2 stain in cancer cells could be a predictor of prognosis in most cases in endometrial cytology with imprint smears. Furthermore, positive expression of COX-2 in cancer cells was related to morphologic features of more aggressiveness tumors.

Tight Junction Protein (Claudin-4) and Inflammatory Regulator (COX-2) Expression in Nasopharyngeal Carcinoma: An Immunohistochemical Study

AbstractBackground: Claudin 4 is one of the tight junction proteins which considered one of the protective barriers that are mostly involved in the regulation of intercellular communication, paracellular transport and apical cell-to-cell adhesion. Over-expression of COX-2 and subsequent increase in prostaglandins (PGs) concentration have emerged in recent years as important players in cancer progression.Aim of Study: To explore immunohisto chemically the expression of both claudin-4 and COX2 in nasopharyngeal carcinoma and correlate their expression with each other and with different clinicopathological parameters.Material and Methods: This retrospective study was done upon formalin fixed, paraffin blocks of 32 nasopharngeal carcinoma cases and 6 non-neoplastic nasopharyngeal epithe-lium. The materials were obtained from archieves of Pathology Departement and Early Cancer Detection Unit (ECDU), Faculty of Medicine, Benha University during the years 2012- 2017. The immunohistochemical stain with Claudin 4 and COX2 was done and evaluated for each case.Results: High expression of claudin 4 was observed in 44% of studied nasopharyngeal cases with statistically signif-icant correlation with tumor stage and distant metastasis (p<0.05). Positive expression of COX2 was detected in 75% of neoplastic group and statistically correlated with depth of tumor invasion, nodal invasion and tumor stage (p<0.05). A statistically significant correlation was detected between overexpression of COX2 and low expression of claudin4 in the studied neoplastic cases (p<0.05).Conclusion: Claudin -4 has different tumorigenic effects besides their known adhesion attributes. Because of that, we believe that claudin 4 with other clinicopahological parameters may be a promising prognostic molecular indicator in na-sopharyngeal cancer cases and can be taken as a novel bi-omarker for the predication of distant metastasis and survival. This work also highlights COX-2 expression's potential as an indicator of cancer progression that can contribute to assess-ment of prognosis and treatment decisions. Therefore, COX-2 inhibitors may have considerable potential as therapeutic agents.

Cyclo-oxygenase-2 Expression Is Associated With Lymph Node Metastasis in Oropharyngeal Squamous Cell Carcinoma Under the New TNM Classification.

This study aimed to investigate p16 and COX2 expression in oropharyngeal squamous cell carcinoma (OPSCC), and evaluate the prognostic role of COX2 expression under the new TNM classification. Biopsy specimens obtained from 75 patients with OPSCC were stained for p16 and COX2 expression immunohistochemically. The results and clinical records were analyzed retrospectively. Fifty-nine patients (79%) were positive for p16. COX2 expression was correlated with poor relapse-free survival in patients overall, and in p16-positive patients. Smoking was positively associated with COX2 expression. Moreover, both positive COX2 expression and anterior wall tumor subsite were independently correlated with lymph node metastasis, which was the only independent prognostic factor in p16-positive OPSCC. The p16-positive rate in this study was comparable with that in the USA and Europe, and higher than that in other Asian countries. COX2 expression might affect the prognosis of p16-positive OPSCC through promoting lymph node metastasis.

Cyclooxygenase-2 Expression Is a Predictive Marker for Late Recurrence in Colorectal Cancer.

Introduction Cyclooxygenase-2 (COX-2) expression is elevated in colorectal cancer (CRC). However, data about the relation between COX-2 expression and the impact on the biologic behavior of recurrent disease are inconclusive as yet. The aim of this study is to investigate the relationship between the status of COX-2 expression in the primary CRC and the characteristics of recurrence after curative resection of stage I to III CRC. Materials and Methods Ninety-eight patients with recurrence in 376 CRC patients, who underwent curative surgery between January 1991 and August 2001, were retrospectively assessed. Immunohistochemical staining, performed for the presence of COX-2 on tissue microarrays, was analyzed. Results Forty-six patients showed elevated COX-2 expression, and 52 patients did not. The mean time to recurrence was significantly longer in the positive group than in the negative group (34.1 months ± 30.0 versus 21.9 months ± 17.4; P = 0.019). Positive COX-2 expression was correlated with late recurrence (>3 years after surgery) [43.5% versus 13.5%; P = 0.001]. In multivariate analysis, COX-2 expression was an independent factor associated with late recurrence (OR 4.656; 95% CI, 1.696 to 12.779; P = 0.003). Recurrence pattern and postrecurrence survival were not different between the two groups. Conclusions Elevated COX-2 expression in itself is not a prognostic factor, but COX-2 expression in tumor tissue may be an independent predictive marker of late recurrence for patients with stage I to III CRC.

COX-2 gene expression and methylation profile in Sapajus apella as an experimental model for gastric adenocarcinoma.

Gastric cancer (GC) remains one of the main causes of cancer-related death worldwide. There are two distinct histological types of GC: diffuse and intestinal. The latter is characterized by the presence of pre-neoplastic lesions. One of the most frequently altered enzymes in intestinal GC is COX-2, an important lesion marker. This work aimed to study COX-2 methylation and expression in N-methyl-N-Nitrosurea (MNU)-induced intestinal GC in six Sapajus apella animals. The partial promoter sequence of S. apella COX-2 gene was obtained and used to identify transcription factors and cis-regulatory element binding sites. The COX-2 methylation pattern was assessed using Methylation-Specific PCR (MSP), and expression was analyzed by immunohistochemistry (IHQ). A total of 20 samples were obtained. A 675 bp fragment of the S. apella COX-2 promoter region was obtained, and it was 99.2% and 68.2% similar to H. sapiens and S. boliviensis, respectively. Similar to humans, several transcription factors and cis-regulatory element binding sites were identified in the S. apella sequence. MSP revealed that all samples were methylated. However, IHQ results demonstrated positive COX-2 expression in all pre-neoplastic and tumoral samples. The results suggest that the analyzed fragment is not crucial in COX-2 regulation of GC in S. apella.

Expressions and clinical significance of COX-2, VEGF-C, and EFGR in endometrial carcinoma.

The article is to study the expressions of COX-2, VEGF-C, and EGFR in endometrial carcinoma as well as its clinical significances. Clinical data of 183 patients with endometrial carcinoma who received surgery as initial treatment in the Nanjing Drum Tower Hospital Affiliated to the Nanjing University Medical School and the Nantong Maternal and Child Health Hospital Affiliated to the Nantong University from January 2005 to December 2010 were retrospectively investigated; 152 out of the 183 patients were closely followed up. Expressions of COX-2, VEGF-C, and EGFR proteins in 152 endometrial carcinoma samples were detected by immunohistochemical S-P assay. A 5-year survival rate of 152 patients was 81.56% (124/152). Positive COX-2 expression rate was 67.76% (103/152), and its positive expression was related to FIGO stage, differentiation degree, and myometrial invasion depth of patients (P<0.05), but not to lymph node metastasis (P>0.05). Positive expression rates of VEGF-C and EGFR were 64.47% (98/152) and 82.24% (125/152), respectively, and their positive expression was associated with FIGO stage, differentiation degree, myometrial invasion depth, and lymphatic metastasis (P<0.05). Correlation analysis on the expression of COX-2 with VEGF-C and of EGFR found that COX-2 was positively correlated with both VEGF-C and EGFR (P<0.05, r s>0). Patient prognosis was associated with the FIGO stage, differentiation degree, and myometrial invasion depth of tumors, as well as the presence or absence of lymph node metastasis (P<0.05) while showing no significant association with the postoperative adjuvant therapy (P>0.05). COX-2, VEGF-C, and EGFR are of significance for determining the FIGO stage, differentiation degree, and myometrial invasion depth of endometrial carcinoma, of which VEGF-C and EGFR are important in determining whether tumors metastasize to lymph nodes. Combined detection of COX-2, EGFR, and VEGF-C can be used as the indices for early diagnosis, recurrence prediction, and outcome evaluation for patients with endometrial carcinoma.

Prognostic and predictive role of COX-2, XRCC1 and RASSF1 expression in patients with esophageal squamous cell carcinoma receiving radiotherapy.

Identification of biomarkers for predicting radiosensitivity would be useful for administering individualized radiotherapy (RT) to patients with esophageal cancer. The aim of the present study was to evaluate the association between cyclooxygenase-2 (COX-2), X-ray repair cross complementing group 1 (XRCC1), ras association domain family 1 (RASSF1) protein expression, clinicopathological characteristics, radiosensitivity and survival rate in 76 patients with esophageal squamous cell carcinoma (ESCC) who were treated with RT. Positive expression of COX-2, XRCC1 and RASSF1 was identified by immunohistochemistry in 81.6, 52.6 and 59.2% of ESCC cases, respectively. Negative COX-2 expression was associated with tumor (T) stage, node (N) stage, clinical stage and complete response (P<0.05), but not with gender, age, tumor location, differentiation degree, lesion length, progression-free survival (PFS) or overall survival (OS; P>0.05). XRCC1 expression was not associated with the clinicopathological features of ESCC, response to RT, PFS or OS. Positive RASSF1 expression was associated with the clinical stage, response to RT, PFS and OS (P<0.05), but not with gender, age, tumor location, T stage, N stage, differentiation degree or the lesion length (P>0.05). In the subgroup analysis, RASSF1 positive/XRCC1 negative expression was correlated with a longer median OS and PFS (P<0.05). Multivariate analyses revealed that the tumor response and RASSF1 expression were significant prognostic factors. Therefore, positive RASSF1 expression is associated with ESCC RT sensitivity, and may be a useful independent prognostic factor for ESCC.

Differential expression of cyclooxygenase-2 in metastatic melanoma affects progression free survival

The possible correlation between cyclooxygenase-2 (COX-2) expression and disease progression in melanoma is still a matter of debate. Analysis of COX-2 expression in 45 lymph node melanoma metastases demonstrates a significant correlation between the percent of expression and progression free survival (PFS). A positive COX-2 expression ≥10% (COX-2high), as opposite to a positive expression ≤9% (COX-2low), translated into a striking significant reduction of PFS of about 3 years. The reduction in PFS correlated neither with BRAFV600E nor with NRASQ61 expression in the analyzed samples. This concept was reinforced by the finding that tumour development in COX-2−/− mice was almost blunted. Similarly, inhibition of COX-2 protein expression in human melanoma cell lines, by using siRNAs technology as well as selective inhibition of COX-2 activity by celecoxib, reduced cellular proliferation and invasiveness. In conclusion we show that COX-2high is a negative prognostic factor in metastatic melanoma. Our study also clarifies that the uncertainty about the role of COX-2 in metastatic malignant melanoma, found in the current relevant literature, is probably due to the fact that a threshold in COX-2 expression has to be reached in order to impact on cancer malignancy. Our findings suggest that COX-2 expression may become an useful diagnostic tool in defining melanoma malignancy as well as argue for a possible therapeutic use of NSAID as add on therapy in selected cases.

Significance of cyclooxygenase-2 elevation in middle cerebral artery for patients with hemorrhagic moyamoya disease.

The etiology and pathogenesis of moyamoya disease (MMD) remain elusive. Some inflammatory proteins, such as cyclooxygenase (COX)-2, are believed to be implicated in the development of MMD. So far, the relationship between COX-2 and MMD is poorly understood and reports on the intracranial vessels of MMD patients are scanty. In this study, tiny pieces of middle cerebral artery (MCA) and superficial temporal artery (STA) from 13 MMD patients were surgically harvested. The MCA and STA samples from 5 control patients were also collected by using the same technique. The expression of COX-2 was immunohistochemically detected and the average absorbance (A) of positively-stained areas was measured. High-level COX-2 expression was found in all layers of the MCA samples from all 5 hemorrhagic MMD patients, while positive but weak expression of COX-2 was observed only in the endothelial layer of the MCA samples from most ischemic MMD patients (6/8, 75%). The average A values of COX-2 in the hemorrhagic MMD patients were substantially higher than those in their ischemic counterparts (t=4.632, P=0.001). There was no significant difference in the COX-2 expression among the "gender" groups, or "radiographic grade" groups, or "lesion location" groups (P>0.05 for all). The COX-2 expression was detected neither in the MCA samples from the controls nor in all STA specimens. Our results suggested that COX-2 was up-regulated in the MCA of MMD patients, especially in hemorrhagic MMD patients. We are led to speculate that COX-2 may be involved in the pathogenesis of MMD and even contribute to the hemorrhagic stroke of MMD patients.

Expression of cyclo-oxygenase-2 enzyme in the tissue samples of patients with various clinicopathological stages of oral leukoplakia and oral squamous cell carcinoma

Aim: The purpose of this study was to evaluate the expression of cyclo-oxygenase-2 (COX-2) enzyme in the tissue samples of patients with various clinicopathological stages of oral leukoplakia and oral squamous cell carcinoma (OSCC). Materials and Methods: The samples for the study were divided into 4 groups. Group A comprised 20 healthy individuals with no habits. Twenty healthy individuals with habitual tobacco usage and no oral lesions were included in Group B. Twenty cases of leukoplakia diagnosed clinically and histopathologically were included in Group C. Staging was done using the modified classification and staging system of oral leukoplakia. Twenty cases of OSCC diagnosed clinically and histopathologically were included in Group D. Immunohistochemical staining was done on these 80 samples (paraffin blocks) for COX-2 expression by indirect method using polymer based Horseradish peroxidase system. Statistical analysis was performed using Kruskal-Wallis test and Spearman's rank correlation test. Results: Significant and proportional increase of COX-2 staining was noted with the increase in the severity of dysplasia. Eighty percent of OSCC expressed COX-2, increasing in its intensity of staining with the decrease in differentiation. Seventy five percent of leukoplakia showed positive COX-2 expression. Only 15% of positive controls were COX-2 positive. No normal mucosa showed positive expression of COX-2. Conclusion: High expression of COX-2 is seen in advanced stages of leukoplakia and OSCC. Hence, COX-2 enzyme increases cell proliferation, promotes angiogenesis and inhibits immune surveillance in carcinogenesis; it can be an early detection marker in oral leukoplakia and a prognostic marker of OSCC.

Expression and prognostic value of COX- 2, p16(INK4A) and p53 in patients with classical Hodgkin lymphoma

目的观察环氧化酶2(COX-2）、周期素依赖激酶抑制剂p16(p16INK4A）、p53蛋白在经典型霍奇金淋巴瘤（cHL）患者中的表达，探讨其与患者预后的相关性。方法收集52例cHL患者的标本，采用免疫组织化学染色法检测相关蛋白，采用原位杂交技术检测EBV及EBV编码的小mRNA（EBER）。结合患者临床及随访资料分析COX-2、p16INK4A、p53蛋白表达与预后的相关性。结果52例患者中男女比例1.6∶1，患者发病年龄22~68岁，均为淋巴结内原发。52例患者中COX-2阳性者28例（53.8%），p16INK4A阳性者25例（48.1%），p53阳性者42例（80.8%）。按照患者年龄（以中位年龄为界）、性别（男／女）、EBV感染（有／无）、B症状（有／无）及Ann-Arbor分期（Ⅰ~Ⅱ/Ⅲ~Ⅳ期）进行分组，分别与COX-2、p16INK4A、p53表达进行相关性分析，结果显示仅p53表达与Ann-Arbor分期有关（P=0.027）。三者间表达的相关性分析结果显示，COX-2表达与p53相关（P=0.008），而与p16INK4A无关（P=0.246），16INK4A与p53表达无关（P=0.958）。单因素分析结果显示COX-2表达是影响患者无事件生存（EFS）的不良预后因素（P=0.003）；采用COX比例风险回归模型进行多因素分析结果显示COX-2表达是影响患者EFS的独立不良预后因素（HR=0.091，95%CI 0.017~0.505，P=0.006）。结论COX-2、p16INK4A、p53在cHL患者中有较高表达率；与患者EBV感染状态均无相关性；COX-2表达是影响患者EFS的独立不良预后因素。

Expression of Cyclooxygenase-2 in Squamous Cell Carcinoma and Keratoacanthoma and its Clinical Significance

Cyclooxygenase (COX), also known as prostaglandin endoperoxide synthase, catalyzes the conversion of arachidonic acid to prostanoids. There are two different isoforms of COX, referred to as COX-1 and COX-2. Overexpression of COX-2 has been demonstrated in various neoplasms. In this study, we plan to utilize COX-2 in understanding the difference of squamous cell carcinoma and keratoacanthoma which have many similarities in both morphological and histological features. The objective of this study is to study the expression of COX-2 in squamous cell carcinoma and keratoacanthoma and to discuss its clinical significance. The expression of COX-2 in 55 cases of skin tumors (including 30 specimens of squamous cell carcinoma, 25 specimens of keratoacanthoma) and 20 normal skin tissues was detected by immunohistochemical technique. The positive expression of COX-2 was found in 73.3% (22/30) of squamous cell carcinoma and 12% (3/25) of keratoacanthoma cases. The positive expression rate of COX-2 in 55 skin tumors (45.5%) was significantly higher than that in normal skin tissues (5%) (χ (2)=10.598%, P<0.05). The expression of COX-2 in squamous cell carcinoma (73.3%) was significantly higher than that in keratoacanthoma (12%) (χ (2)=20.69, P<0.05). COX-2 overexpression may play a potential role in the pathogenesis of skin tumors. The positive expression rate of COX-2 is associated with the malignant degree of the tumor, and also it may help differentiating squamous cell carcinoma from keratoacanthoma.

Expression of COX-2 and HER-2 in colorectal cancer and their correlation.

To detect the expression of COX-2 and HER-2 in colorectal cancer and to analyze their correlation and clinical significance. A total of 1026 colorectal cancer surgical specimens were collected from patients treated from December 2002 to December 2007 at the First Affiliated Hospital of Anhui Medical University. All specimens were made into 4-μm slices. The expression of COX-2 and HER-2 were detected by immunohistochemistry using the streptavidin-biotin-peroxidase method. The correlations between COX-2 and HER-2 expression and colorectal cancer clinical features were analyzed. The positive rates of COX-2 and HER-2 expression in colorectal cancer were 77.97% (800/1026) and 46.20% (474/1026), respectively. There was a significant correlation between COX-2 and HER-2 expression in colorectal cancer (P < 0.05). In patients with tumor size ≥ 5 cm, the positive rates of COX-2 and HER-2 expression were 81.48% (308/378) and 57.94% (219/378), respectively. In patients with serosal invasion, the positive COX-2 and HER-2 expression rates were 80.53% (612/760) and 49.21% (374/760), respectively. In patients with lymph node metastasis, the positive expression rates were 85.04% (506/595) and 54.62% (325/595), respectively, and the positive expression rates differed significantly between patients with lymph node metastasis and those without (P < 0.05). In patients with Duke's C and D colorectal cancer, the positive COX-2 and HER-2 expression rates were 82.80% (443/535) and 57.94% (310/535), respectively. In patients with poorly differentiated colorectal cancer, the positive expression rates were 74.49% (210/282) and 52.84% (149/282), respectively (P < 0.05). In patients with distant metastasis, the positive expression rates were 82.27% (116/141) and 53.90% (76/141), respectively (P < 0.05). These findings suggest that COX-2 and HER-2 have synergistic effects in colorectal cancer. COX-2 and HER-2 expression had no significant correlation with sex, age, or tumor location. COX-2 and HER-2 are important markers for invasion and metastasis of colorectal cancer, and they act together to regulate the invasion and metastasis of colorectal cancer.

Abnormal COX2 protein expression may be correlated with poor prognosis in oral cancer: a meta-analysis.

Background. The prognostic significance of COX2 for survival of patients with oral cancer remains controversial. Thus, the meta-analysis was performed in order to identify COX2 expression impact on prognosis of oral cancer. Method. Relevant literatures were searched using the following electronic databases without any language restrictions: Web of Science, the Cochrane Library Database, PubMed, EMBASE, CINAHL, and CBM. Version 12.0 STATA software (Stata Corporation, College Station, Texas, USA) was used for the current meta-analysis. Odds ratios (ORs) and hazard ratios (HRs) with their corresponding 95% confidence interval (95% CI) were also calculated to clarify the correlation between COX2 expression and prognosis of oral cancer. Results. Final analysis of 979 oral cancer patients from 12 clinical cohort studies was performed. The meta-analysis results show that COX2 expression in cancer tissues was significantly higher than those in normal and benign tissues (all P < 0.05). Combined HR of COX2 suggests that positive COX2 expression has a shorter overall survival (OS) than those of negative COX2 expression (P < 0.05). Conclusion. The meta-analysis study shows that elevated COX2 expression may be associated with the pathogenesis of oral cancer and with a worse prognosis in oral cancer patients.