Cyclooxygenase-2 Expression Is Related With Localization, Proliferation, and Overall Survival in Canine Melanocytic Neoplasms

2011 ◽  
Vol 48 (6) ◽  
pp. 1204-1211 ◽  
Author(s):  
C. M. Martínez ◽  
C. Peñafiel-Verdú ◽  
M. Vilafranca ◽  
G. Ramírez ◽  
M. Méndez-Gallego ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mitotic Index ◽  
Tumor Location ◽  
Cyclooxygenase 2 ◽  
Ki 67 ◽  
Melanocytic Tumors ◽  
Oral Neoplasms ◽  
Survival Frequency ◽  
Cox 2 ◽  
Proliferative Indices

A direct relationship has been firmly established between cyclooxygenase-2 (COX-2) expression and malignant behavior in human melanoma. This report examines the relationship between COX-2 expression and tumor location, mitotic and proliferative indices, degree of T CD3+ lymphocyte infiltration, overall survival, and frequency of recurrence and metastasis of 57 melanocytic tumors (25 oral and 32 cutaneous). COX-2 was highly or moderately expressed in 88% of oral neoplasms (22 of 25), whereas for their cutaneous counterparts, COX-2 expression was low or insignificant in 75% of cases (24 of 32). High and moderate COX-2 expression levels were observed in 73% of melanocytic tumors with a mitotic index ≥ 3 per 10 high-power fields (26 of 36), whereas in 81% of tumors with a mitotic index < 3 (17 of 21), expression was mild or absent. There were 41 cases with known clinical outcomes; of those showing high, moderate, and mild COX-2 expression, 83.3% (10 of 12), 37.5% (3 of 8), and 25% (2 of 8) died, respectively, whereas 100% of animals showing no COX-2 expression (13 of 13) were still alive at the last follow-up. COX-2 expression was statistically correlated with tumor location, mitotic and percentage Ki-67 proliferative indices, and overall survival, frequency of neoplastic recurrence and metastasis. Regression analysis also showed disease-specific predictive value for COX-2 expression for subjects with melanocytic neoplasms. Additionally, only high COX-2 expression showed significant differences in overall survival, in comparison with moderate, mild, or absent expression. These results suggest that high COX-2 expression may be considered a prognostic biomarker and potentially as a target for therapeutic and preventive strategies in canine melanocytic neoplasms.

scholarly journals Histomorphological and Immunophenotypic Characterization of Feline Injection Site-Associated Sarcoma

2021 ◽  
Vol 49 ◽  
Author(s):  
Sílvia Teixeira Pereira ◽  
Conrado Oliveira Gamba ◽  
Rodrigo Santos Horta ◽  
Rúbia Monteiro de Castro Cunha ◽  
Gleidice Eunice Lavalle ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Grade ◽  
Histologic Grade ◽  
Biological Behavior ◽  
Histological Subtypes ◽  
Recurrence Rates ◽  
Ki 67 ◽  
Nerve Sheath ◽  
Cox 2 ◽  
Grade Iii

Background: Feline Injection Site-Associated Sarcoma (FISS) is a mesenchymal neoplasia of aggressive behavior that develops in sites where vaccine or drugs were administered. FISS is clinically characterized by the appearance of a solitary firm nodule or a diffuse mass, adhered to tissues, in regions associated to vaccine or drug applications. Despite low prevalence, tumor recurrence rates can reach 80%. FISS present more aggressive histological characteristics when compared to sarcomas not associated to injection sites. The aim of this paper is to contribute towards the understanding of the biological behavior of FISS.Materials, Methods & Results: Sixteen samples of FISS were analyzed. Fibrosarcomas were the most frequent histological subtype (62.5%). Malignant peripheral nerve sheath tumor was diagnosed in 18.75% cases. Ten (62.5%) FISS were classified as grade II; 4/16 (25%) grade I, and 2/16 (12.5%) grade III. Cox-2 overexpression occurred in 3/16 (18.75%) samples, with positive correlation between Cox-2 expression and cellularity (r = 0.696, P = 0.003). Mitotic index lower than 9 events was found in 11/16 (68.7%) samples and between 10 and 19 mitotic events in 5/16 (31.3%) cases. Mean Ki-67 expression was 2.39 ± 2.48%. FISS characterized as fibrosarcomas presented longer overall survival (median 545 days) than other histological subtypes (median 130.5 days) [P = 0.01].Discussion: Patients with FISS generally present with larger nodules than those with sarcomas not associated to injections, suggesting a challenge for pet owners to note subcutaneous tumors in the interscapular region, in addition to the aggressive biological behavior of FISS. The influence of size on prognosis remains controversial. An association between histologic grade and the development of metastasis has been observed, with patients with grade III FISS associated with an increase in the metastatic rate. The present study did not find a correlation between overall survival and histologic grade. A positive correlation between the presence of giant multinucleated cells and tumor grade has been observed.Despite the absence of such correlation in the present study, possibly due to a small sample, a trend for higher frequency of giant cells in advanced histologic grade was observed. Cox-2 expression in 81.75% and overexpression in 18.75% of our samples contrasts with the 64% Cox-2 expression and the absence of Cox-2 expression found by other authors. A positive moderate correlation between cellularity and Cox-2 expression was also observed, while another study did not find a correlation of Cox-2 expression with tumor grade, recurrence rates or overall survival. Cox metabolites such as prostaglandins can enhance cellular proliferation, inhibit apoptosis, induce angiogenesis, alter cellular adherence to facilitate metastatic development and inhibit immune surveillance. In the present study, no correlation was found between Cox-2 and angiogenesis in FISS. Our findings demonstrated low immunolabeling for Ki-67. A previous study analyzed 52 samples of FISS, 51% of them considered grade III, with a mean Ki-67 labeling of 14%. The lower Ki-67 staining in the samples of the present study may be related to the lower number of samples of grade III FISS or to a difference in the studied population. Fibrosarcomas are associated with better prognosis than other histological subtypes. Furthermore, malignant peripheral nerve sheath tumors were diagnosed as a possible histological subtype of FISS.

scholarly journals Stromal, rather than epithelial cyclooxygenase-2 (COX-2) expression is associated with overall survival of breast cancer patients

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Justyna Urban ◽  
Łukasz Kuźbicki ◽  
Grzegorz Szatkowski ◽  
Agata Stanek-Widera ◽  
Dariusz Lange ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Cyclooxygenase 2 ◽  
Breast Cancer Patients ◽  
Cox 2

scholarly journals Mitotic and Proliferative Indices in WHO Grade III Meningioma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3351
Author(s):  
Andrea Daniela Maier ◽  
Christian Beltoft Brøchner ◽  
Jiri Bartek Jr. ◽  
Frank Eriksson ◽  
Heidi Ugleholdt ◽  
...  
Keyword(s):  
Mitotic Index ◽  
Hot Spot ◽  
Progression Free Survival ◽  
Ki 67 ◽  
Who Grade ◽  
Free Survival ◽  
Phosphohistone H3 ◽  
Proliferative Indices ◽  
Who Grade Iii ◽  
Grade Iii

Meningiomas with inherently high mitotic indices and poor prognosis, such as WHO grade III meningiomas, have not been investigated separately to establish interchangeability between conventional mitotic index counted on H&E stained slides (MI) and mitotic index counted on phosphohistone-H3 stained slides (PHH3 MI). This study investigates the agreement of MI and PHH3 MI and to analyze the association of progression-free survival (PFS) and MI, PHH3 MI, and the proliferative index (PI, Ki-67) in WHO grade III meningioma. Tumor specimens from 24 consecutive patients were analyzed for expression of Ki-67, PHH3 MI, and MI. Quantification was performed independently by two observers who made replicate counts in hot spots and overall tumor staining. Repeatability in replicate counts from MI and PHH3 MI was low in both observers. Consequently, we could not report the agreement. MI, PHH3 MI and hot spot counts of Ki-67 were associated with PFS (MI hot spot HR = 1.61, 95% CI 1.12–2.31, p = 0.010; PHH3 MI hot spot HR = 1.59, 95% CI 1.15–2.21, p = 0.006; Ki-67 hot spot HR = 1.06, 95% CI 1.02–1.11. p = 0.004). We found markedly low repeatability of manually counted MI and PHH3 MI in WHO grade III meningioma, and we could not conclude that the two methods agreed. Subsequently, quantification with better repeatability should be sought. All three biomarkers were associated with PFS.

Epigenetic Silencing of Cyclooxygenase-2 Affects Clinical Outcome in Gastric Cancer

2007 ◽  
Vol 25 (31) ◽  
pp. 4887-4894 ◽  
Author(s):  
Michiel F.G. de Maat ◽  
Cornelis J.H. van de Velde ◽  
Naoyuki Umetani ◽  
Pieter de Heer ◽  
Hein Putter ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Pilot Study ◽  
Patient Group ◽  
Methylation Status ◽  
Gene Promoter ◽  
Promoter Hypermethylation ◽  
Cyclooxygenase 2 ◽  
Time To Recurrence ◽  
Cox 2

PurposeOverexpression of cyclooxygenase-2 (COX-2) in gastric cancer has been shown to enhance tumor progression. We investigated whether silencing by promoter region hypermethylation of the COX-2 gene contributes to disease outcome in gastric cancer.Materials and MethodsCOX-2 methylation status was initially assessed by capillary array electrophoresis methylation–specific polymerase chain reaction (CAE-MSP) and COX-2 protein expression by immunohistochemistry (IHC) in 40 primary gastric cancer tissues in a pilot study. Prognostic end points of correlative studies of COX-2 methylation status were time to recurrence, overall survival, and standard clinicopathologic features. CAE-MSP analysis was then validated in a second independent gastric cancer population (n = 137).ResultsCOX-2 methylation was detected in 23% and 28% of the pilot and validation patient groups, respectively. COX-2 expression (IHC) in gastric tumors inversely correlated with COX-2 gene methylation status in the pilot study (P = .02). COX-2 methylation in tumors was significantly associated with lower T, N, and TNM stage in the validation patient group (P = .02, P = .006, and P = .008, respectively). Patients with COX-2 methylated tumors had significantly longer time to recurrence and improved overall survival in a multivariate analysis in the validation patient group (hazard ratio[HR], 0.49; 95% CI, 0.24% to 0.99%; HR, 0.62; 95% CI, 0.38% to 0.99%, respectively).ConclusionHypermethylation of COX-2 gene promoter was identified as an independent prognostic factor in gastric cancer patients. The results suggest promoter hypermethylation to be an important regulatory mechanism of COX-2 expression in gastric cancer and an important prognostic biomarker.

Predictive Value of Tumor Proliferative Indices in Periampullary Cancers: Ki-67, Mitotic Activity Index (MI) and Volume Corrected Mitotic Index (M/V) Using Tissue Microarrays

2010 ◽  
Vol 34 (9) ◽  
pp. 2115-2121 ◽  
Author(s):  
Mark M. Aloysius ◽  
Shivanthi J. De Silva Hewavisenthi ◽  
Timothy E. Bates ◽  
Brian J. Rowlands ◽  
Dileep N. Lobo ◽  
...  
Keyword(s):  
Mitotic Activity ◽  
Mitotic Index ◽  
Predictive Value ◽  
Activity Index ◽  
Tissue Microarrays ◽  
Ki 67 ◽  
Mitotic Activity Index ◽  
Proliferative Indices

scholarly journals Prognostic significance of histopathological factors in survival and recurrence of atypical carcinoid tumours

2021 ◽  
Author(s):  
Eva-María García-Fontán ◽  
Miguel-Ángel Cañizares-Carretero ◽  
Montserrat Blanco-Ramos ◽  
Jose-María Matilla-González ◽  
Rommel Carrasco-Rodríguez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Mitotic Index ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Nodal Involvement ◽  
Ki 67 ◽  
Disease Free Interval ◽  
Free Interval ◽  
Disease Free

Abstract OBJECTIVES Atypical carcinoids are neuroendocrine neoplasms of intermediate degree and low frequency. The aim of this study is to analyse their clinical characteristics and the importance of different histopathological factors in their prognosis. METHODS Multicentre cooperative group EMETNE prospectively reviewed 153 patients operated on between 1998 and 2016 with diagnosis of atypical carcinoids. Clinical variables and histopathological features were assessed. RESULTS Mean age was 54.36 years, similar for both genders. Concerning pathological study, mean tumour size was 31.7 mm. Rosettes were presented in 17% of the cases and tumoural necrosis in 23.3%. The cell proliferation factor Ki-67 index was 10.7%. The 2- and 5-year overall survival rates were 95.8% and 88.9%, respectively. In the univariate study, statistically significant differences in survival were found for each of the categories of T, N and M factors. Mitotic index and quantification of expression of Ki-67 showed influence in overall survival, although without statistical significance. In the multivariate analysis, factors N, M and mitotic index behaved as independent prognostic factors related to survival. Median disease-free interval in the series was 163.35 months. In cases with loco-regional recurrence, 53% had positive hiliar or mediastinal nodal involvement at the time of the surgery. In the univariate analysis, we observed statistically significant differences in disease-free interval in patients with nodal involvement (P = 0.024) and non-anatomical resections (P = 0.04). Histological characteristics showed no statistically significant differences in disease-free interval. CONCLUSIONS Lymph node involvement, the development of distant metastasis and mitotic index, more than Ki-67 determination, were shown as independent prognostic factors related to survival of these patients.

scholarly journals Original Article HUBUNGAN EKSPRESI CYCLOOXYGENASE-2 (COX-2) DENGAN DISEASE FREE SURVIVAL DAN OVERALL SURVIVAL PADA PENDERITA KANKER PAYUDARA

2019 ◽  
Vol 12 (1) ◽  
pp. 102
Author(s):  
Prihantono Prihantono ◽  
Juhamran Juhamran ◽  
Zaenal Abidin ◽  
Haryasena Haryasena ◽  
Salman Ardi Syamsu
Keyword(s):  
Overall Survival ◽  
Disease Free Survival ◽  
Cyclooxygenase 2 ◽  
Free Survival ◽  
Cox 2 ◽  
Disease Free

Cyclooxygenase-2 (COX-2) berperan dalam pertumbuhan tumor dan metastasisnya yang berdampak pada buruknya prognosis. Tujuan penelitian ini untuk mengetahui hubungan ekspresi COX-2 terhadap disease free survival dan overall survival pada pasien kanker payudara. Penelitian ini bersifat observasional menggunakan desain kohort dengan periode follow up selama 24 bulan. Hasil: Ekspresi COX-2 ditemukan pada 21 sampel (42%) dari 50 pasien kanker payudara. Selama follow up 24 bulan, lama DFS pada COX-2 negatif (20,1 bulan) lebih lama dibandingkan pada COX-2 positif (14,0 bulan) dan menunjukkan hubungan yang signifikan (p<0,01). Lama OS pada COX-2 negatif (22,6 bulan) lebih lama dibandingkan pada COX-2 positif (17,8 bulan) yang juga menunjukkan hubungan yang signifikan (p<0,01). Terdapat hubungan yang signifikan antara ekspresi COX-2 dengan disease free survival dan overall survival pada pasien kanker payudara. COX-2 bisa dijadikan salah satu faktor prognostik kanker payudara.

scholarly journals Immunohistochemical expression of Cyclooxygenase 2 reflects the proliferative activity in the epithelium of odontogenic lesions

2022 ◽  
Vol 10 (1) ◽  
Author(s):  
Vani Verma ◽  
Chetana Chandrashekar ◽  
Raghu Radhakrishnan ◽  
Monica Charlotte Solomon
Keyword(s):  
Epithelial Cells ◽  
Dentigerous Cyst ◽  
Cyclooxygenase 2 ◽  
Odontogenic Keratocyst ◽  
Odontogenic Cysts ◽  
Radicular Cyst ◽  
Chi Square ◽  
Ki 67 ◽  
Odontogenic Epithelium ◽  
Cox 2

Purpose:  Odontogenic cysts and tumors comprise a major component of lesions of the oral and maxillofacial region. The pathogenesis of these lesions involves the interaction between the odontogenic epithelium and the ectomesenchyme. However, the clinical behavior of these biological entities is unpredictable. The aim of this study was to evaluate the role of Cyclooxygenase 2 (COX-2) in the pathogenesis and prognostication of odontogenic lesions.Material and method:  : In this study formalin-fixed paraffin-embedded tissue section of Odontogenic Keratocyst (n=10) Dentigerous cyst (n=10), Radicular cyst (n=10) and unicystic ameloblastoma (n=10) were immunohistochemically stained with COX-2 (NCL2-COX-2- 4H12) and with Ki 67 (Ki-67 GM001) using standard staining protocols. The cytoplasmic expression of COX-2 in all the lesions was semi-quantitatively assessed. The pattern of expression of COX-2 among the different odontogenic lesions was statistical analyzed using the ANOVA test and the chi-square test.Results: All the 40 odontogenic lesions that were evaluated expressed COX-2 immunohistochemically. A high number of odontogenic epithelial cells expressed COX-2 in most of the odontogenic keratocyst, radicular cyst and unicystic ameloblastomas. The expression of COX-2 was significantly (p=0.036) higher in Unicystic Ameloblastomas and Radicular cyst compared to that of Odontogenic Keratocyst and the dentigerous cyst.Conclusion: The recognition that expression of COX-2 by odontogenic epithelial cells may indeed shed a new light on the biological mechanisms involved in the development of these benign yet aggressive lesions of the jaws. An insight into the molecular interactions occurring in the odontogenic epithelium will aid in better management of these lesions. 

scholarly journals Expression of Osteopontin and Cyclooxygenase-2 in relation to cellular proliferation, in non-tumor colonic mucosa, colonic adenomas and colon adenocarcinoma

2021 ◽  
Vol 10 (1) ◽  
pp. 3-15
Author(s):  
Inés Benedetti Padron ◽  
Paola Lecompte ◽  
Lía Barrios Garcia
Keyword(s):  
Cell Proliferation ◽  
Colonic Mucosa ◽  
Colon Adenocarcinoma ◽  
Cyclooxygenase 2 ◽  
Proliferation Index ◽  
Ki 67 ◽  
Colonic Adenomas ◽  
Significant Difference ◽  
Cox 2 ◽  
Cell Proliferation Index

Introduction: the participation of Cyclooxygenase-2 (COX-2) and Osteopontin has been postulated in the development of colon cancer, which play an important role in the progression and could be biomarkers for its prognosis, but their role remains controversial. Objective: to determine and to compare the expression of Osteopontin and COX-2 in non-tumor colonic mucosa, colonic adenomas and colon adenocarcinoma, in relation to the cell proliferation index. Methods: the immunohistochemical expression of COX-2, Osteopontin and Ki-67 in formalin fixed paraffin embedded tissue of non-tumor colonic mucosa, colonic adenomas and colon adenocarcinoma were determined and compared. Results: were included 65 cases: 19 of non-tumor colonic mucosa, 13 colonic adenomas and 33 colon adenocarcinomas. There was increased expression of Ki-67 in dysplastic and tumor cells. There was positive expression for COX-2 in adenomas (30.7%) and adenocarcinomas (27.3%), without significant difference between non- tumor colonic mucosa, adenomas and adenocarcinoma (p = 0.888). Osteopontin showed more frequent positivity in adenocarcinomas (72.7%) and adenomas (84.6%) than in non-tumor mucosa (10.5%), (p = <0.0001), without significant differences in its expression between subtypes and grades of adenoma dysplasia, nor between grades of differentiation, extension and proliferation of adenocarcinomas. There was a significant association between Osteopontin expression and the cell proliferation index. No association was observed between the expression of COX-2 and Osteopontin (p = 0.96). Conclusions: Osteopontin overexpression in colon adenocarcinoma and adenomas in comparison with non-tumor colonic mucosa, and its significant relationship with the cell proliferation index, constitutes additional evidence of its possible participation in the colonic carcinogenesis process.

The expression of multiple proteins as prognostic factors in human colorectal cancer: The correlation between cathepsin D, p53, Cox-2, EGFR, C-erbB2, and Ki-67 expression.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 502-502 ◽  
Author(s):  
In Kyu Lee ◽  
Hyung Jin Kim
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Cathepsin D ◽  
Poor Prognosis ◽  
Single Gene ◽  
Overall Survival Rate ◽  
Ki 67 ◽  
Free Survival ◽  
Cox 2

502 Background: This study aimed to establish a correlation between the expression of cathepsin D; p53; Cox-2; EGFR; C-erbB2; Ki-67 protein and the prognosis of colorectal cancer patients. Methods: Tissue samples were collected from 266 patients who underwent surgery for colorectal cancer from January 2006 to December 2007. The expression of the six proteins was determined using immunohistochemical staining of paraffin-embedded tissue specimens. Results: Cathepsin D, p53, Cox-2, EGFR, C-erbB2, and Ki-67 expression was detected in 38.7%, 60.9%, 37.6%, 35.7%, 30.1%, and 74.4% of the samples, respectively. The expression of cathepsin D was significantly correlated with reduced cancer-free survival (p=0.036) and overall survival (p=0.003), whereas the expression of the other proteins could not be correlated. In a multivariate analysis, after adjusting for age, sex, and stage, cathepsin D expression was found to be an independent prognostic factor for a short overall survival(HR=8.55, 95% CI 1.07–68.49). Furthermore, patients with tumors expressing four or more of the proteins had a significantly decreased cancer-free survival rate (p=0.006) and overall survival rate (p=0.002), when compared with patients expressing fewer than four of the proteins Conclusions: In this study, the expression of CD was correlated with a poor prognosis in terms of the cancer-free survival and the overall survival rate. Importantly, the high hazard ratio (HR=8.55) associated with CD expression from the multivariate analysis, even after adjusting for the tumor stage, demonstrates its potential as an independent, single-gene prognostic factor. The expression of four or more of the examined proteins was significantly correlated with a poor prognosis, even after adjusting for the stage. Currently, the prognostic value of a single gene marker in CRCA is very controversial, but based on these results, we believe that the number of expressed genes/proteins may be helpful in identifying patients with both early-stage cancer and a potentially poor prognosis, which will help to determine if adjuvant chemotherapy is necessary.

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