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

Background Emerging 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 findings Formalin-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). Conclusion This 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.

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Cyclooxygenase-2 Expression in Equine Tumors

Veterinary Pathology ◽

10.1354/vp.45-6-825 ◽

2008 ◽

Vol 45 (6) ◽

pp. 825-828 ◽

Cited By ~ 16

Author(s):

D. H. Thamm ◽

E. J. Ehrhart ◽

J. B. Charles ◽

Y. A. Elce

Keyword(s):

Antitumor Activity ◽

Squamous Cell Carcinomas ◽

Cyclooxygenase 2 ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Immunohistochemical Methods ◽

Cox 2 ◽

Strong Immunoreactivity ◽

Formalin Fixed ◽

Pharmacologic Inhibition

The enzyme cyclooxygenase-2 (COX-2) is expressed in some tumor and stromal tissues, and catalyzes production of prostaglandins with growth stimulatory, antiapoptotic, proangiogenic, and immunosuppressive properties. Pharmacologic inhibition of COX-2 is associated with antitumor activity in various human and canine malignancies. The purpose of this study was to assess COX-2 expression in a series of equine sarcoids, melanomas, and squamous-cell carcinomas (SCC). COX-2 expression was assessed in formalin-fixed paraffin-embedded tissues from 14 sarcoids, 11 melanomas, and 37 SCC that represent various anatomic sites by using standard immunohistochemical methods. COX-2 was expressed in 2 of 14 sarcoids, 7 of 11 melanomas, and 32 of 37 SCC, 56% of which demonstrated moderate-to-strong immunoreactivity. There were no differences in expression between anatomic sites. In conclusion, most equine SCC and many melanomas appear to express COX-2 and thus could respond to COX-2 inhibitor therapy.

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Release of Cyclooxygenase-2 and Lipoxin A4 from Blood Leukocytes in Aspirin-exacerbated Respiratory Disease

Allergy & Rhinology ◽

10.2500/ar.2016.7.0172 ◽

2016 ◽

Vol 7 (3) ◽

pp. ar.2016.7.0172

Author(s):

Ajnacska Rozsasi ◽

Akos Heinemann ◽

Tilman Keck

Keyword(s):

Respiratory Disease ◽

Mononuclear Cells ◽

Cyclooxygenase 2 ◽

Control Group ◽

Peripheral Blood Mononuclear ◽

Control Subjects ◽

Aspirin Exacerbated Respiratory Disease ◽

Blood Mononuclear Cells ◽

Cox 2 ◽

The Difference

Background The release of cyclooxygenase-2 (COX-2) and lipoxin A4 (LXA4) from blood mononuclear cells in patients with aspirin-exacerbated respiratory disease (AERD) is only partially understood. Objective To investigate the presence of COX-2 and LXA4 in peripheral blood mononuclear cells (PBMC) derived from patients with AERD and with nasal polyps (NP) (designated as the AERD-NP group), patients with NP without AERD (the NP group), and healthy controls without sinus disease (the control group). Methods Blood was taken from 14 patients in the AERD-NP group, 6 patients in the NP group, and 8 healthy subjects in the control group. After culturing of human PBMC, the presence of COX-2 protein and LXA4 (ELISA) was detected in the supernatant, and the results were compared among the groups. Results COX-2 and LXA4 were detectable after culturing of PBMC in all patients in the AERD-NP and NP groups and in the control subjects. COX-2 was highest in the patients in the AERD-NP group, but the difference was not significant compared with patients with non-AERD polyp and with the control subjects. LXA4 was also highest in the AERD-NP group, but the difference was also not significant compared with the patients who were non-AERD polyp and the control subjects. Conclusion Neither the release of COX-2 or LXA4 was different between the patients with AERD and with NPs, the patients without AERD and with NPs, and the healthy control group. The release of these proteins in AERD needs further investigation.

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Phase III Randomized Trial Assessing Rofecoxib in the Adjuvant Setting of Colorectal Cancer: Final Results of the VICTOR Trial

Journal of Clinical Oncology ◽

10.1200/jco.2010.29.6244 ◽

2010 ◽

Vol 28 (30) ◽

pp. 4575-4580 ◽

Cited By ~ 62

Author(s):

Rachel S. Midgley ◽

Christopher C. McConkey ◽

Elaine C. Johnstone ◽

Janet A. Dunn ◽

Justine L. Smith ◽

...

Keyword(s):

Colorectal Cancer ◽

Colorectal Carcinogenesis ◽

Phase Iii ◽

Adjuvant Setting ◽

Case Control Studies ◽

Curative Surgery ◽

Tissue Samples ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Cox 2

Purpose Laboratory and case-control studies suggest a pivotal role for the cyclooxygenase-2 (COX-2) pathway in colorectal carcinogenesis. The purpose of this study was to test whether the COX-2 inhibitor rofecoxib could reduce recurrence and improve survival when administered in the adjuvant setting of colorectal cancer (CRC). Patients and Methods Patients who had undergone potentially curative surgery and completion of adjuvant therapy for stage II and III CRC were randomly assigned to receive rofecoxib (20 mg daily) or placebo. The primary end point was overall survival (OS). Where formalin-fixed paraffin-embedded tumor tissue samples were available, COX-2 expression was evaluated by immunohistochemistry and correlated with clinical outcome. Results Two thousand four hundred thirty-four patients were entered onto the study. The trial was terminated early because of the worldwide withdrawal of rofecoxib. At this point, 1,167 patients had received rofecoxib and 1,160 patients had received placebo for median treatment durations of 7.4 and 8.2 months, respectively. For the rofecoxib and placebo arms, median follow-up times were 4.84 and 4.85 years, with 241 and 246 deaths and 297 and 329 recurrences, respectively. No difference was demonstrated in OS (hazard ratio [HR] = 0.97; 95% CI, 0.81 to 1.16; P = .75) or recurrence (HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) comparing the two groups. Tumor COX-2 expression by immunohistochemistry was assessed for 871 patients, but neither prognostic nor predictive effects were observed. Conclusion In this study of abbreviated therapy in the adjuvant setting of CRC, rofecoxib did not improve OS or protect from recurrence in unselected patients. In addition, COX-2 expression did not correlate with prognosis overall or predict effectiveness of COX-2 inhibitors.

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BRCA1 and MAD2 Are Coexpressed and Are Prognostic Indicators in Tubo-ovarian High-Grade Serous Carcinoma

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001214 ◽

2018 ◽

Vol 28 (3) ◽

pp. 472-478 ◽

Cited By ~ 3

Author(s):

Tara Byrne ◽

Laura Nelson ◽

James P. Beirne ◽

Daniel Sharpe ◽

Jennifer E. Quinn ◽

...

Keyword(s):

Overall Survival ◽

Staining Intensity ◽

Prognostic Indicators ◽

Serous Carcinoma ◽

Nuclear Staining ◽

High Grade ◽

Strongly Correlated ◽

Brca1 Expression ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded

ObjectivesThe aim of this study was to investigate the relationship between BRCA1 and mitotic arrest deficiency protein 2 (MAD2) protein expression, as determined by immunohistochemistry, and clinical outcomes in epithelial ovarian carcinoma (EOC).MethodsA tissue microarray consisting of 94 formalin-fixed paraffin-embedded EOC with fully matched clinicopathological data were immunohistochemically stained with anti-BRCA1 and anti-MAD2 antibodies. The cores were scored in a semiquantitative manner evaluating nuclear staining intensity and extent. Coexpression of BRCA1 and MAD2 was evaluated, and patient survival analyses were undertaken.ResultsCoexpression of BRCA1 and MAD2 was assessed in 94 EOC samples, and survival analysis was performed on 65 high-grade serous carcinomas (HGSCs). There was a significant positive correlation between BRCA1 and MAD2 expression in this patient cohort (P < 0.0001). Both low BRCA1 and low MAD2 are independently associated with overall survival because of HGSC. Low coexpression of BRCA1 and MAD2 was also significantly associated with overall survival and was driven by BRCA1 expression.ConclusionBRCA1 and MAD2 expressions are strongly correlated in EOC, but BRCA1 expression remains the stronger prognostic factor in HGSC.

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Optimal Probe Size and Fixation Time for the Detection of Porcine Circovirus–2 DNA by in Situ Hybridization in Formalin-Fixed, Paraffin-Embedded Tissue

Journal of Veterinary Diagnostic Investigation ◽

10.1177/104063870902100509 ◽

2009 ◽

Vol 21 (5) ◽

pp. 649-654 ◽

Cited By ~ 7

Author(s):

Yooncheol Ha ◽

Chanhee Chae

Keyword(s):

In Situ Hybridization ◽

Lymph Nodes ◽

Porcine Circovirus ◽

Fixation Time ◽

Formalin Fixed Paraffin ◽

Probe Size ◽

Formalin Fixed Paraffin Embedded ◽

The Difference ◽

Formalin Fixed

Probe size and fixation time for detecting Porcine circovirus–2 (PCV–2) by in situ hybridization in formalin-fixed, paraffin-embedded lymph nodes from experimentally infected pigs were optimized. In situ hybridization using a 169–base pair (bp) probe detected significantly fewer PCV–2–positive cells than when using 8 other larger probes ( P < 0.05). The difference in hybridization intensity between smaller probes (169 and 225 bp) and larger probes (416, 473, 571, 631, 693, and 753 bp) was statistically significant ( P < 0.05). The PCV–2–positive cells were consistently detected in lymph nodes fixed up to 3 days; thereafter, the number of positive cells declined. The PCV–2–positive cells were detected in lymph nodes fixed for up to 730 days. The difference in hybridization intensity between samples fixed for a short term (1 or 3 days) and a longer term (4–730 days) was statistically significant ( P < 0.05). The data demonstrates that the optimal probe size and fixation time for detecting PCV–2 in formalin-fixed, paraffin-embedded lymph nodes is 473 bp and 1–3 days, respectively.

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