Cyclooxygenase-2 Expression and Clinical Outcome in Gastrointestinal Stromal Tumors

Stewart, Ashley; Heslin, M.; Arch, Jorge; Jhala, Nirag; Gómez, Fernando; Bland, Kirby I.; Arnoletti, J. Pablo

doi:10.1016/j.gassur.2005.05.012

Cited by 6 publications

(11 citation statements)

References 23 publications

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“…Although cyclooxygenase‐2 (COX‐2) is upregulated in humans with GISTs and some literature suggests an association with a malignant tumor phenotype, this relationship has not been definitively established . Whether humans with GISTs that express high COX‐2 activity have a worse outcome, or benefit from COX‐2 inhibition, are also unanswered questions . To our knowledge, no literature exists examining COX‐2 expression in GISTs in dogs, although its expression has been demonstrated in a variety of carcinomas in dogs, including intestinal and colorectal adenocarcinomas .…”

Section: Discussionmentioning

confidence: 99%

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs

Berger

Johannes

Jergens

et al. 2018

Veterinary Internal Medicne

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BackgroundGastrointestinal stromal tumors (GISTs) are uncommon intestinal neoplasms in the dog. Literature regarding adjunctive therapy for GISTs in dogs is sparse. High‐risk GISTs in humans respond to tyrosine kinase inhibition in the adjuvant setting.ObjectivesTo review cases of toceranib phosphate use in dogs with GISTs and provide initial assessment of possible biological activity. A secondary aim was to evaluate patient and tumor characteristics for possible prognostic value.AnimalsTwenty‐seven dogs with confirmed GISTs based on histopathology and immunohistochemistry treated with toceranib.MethodsRetrospective study in which cases of toceranib use in dogs with GIST were solicited using the American College of Veterinary Internal Medicine Oncology and Small Animal Internal Medicine listservs.ResultsFive of 7 dogs with gross disease experienced clinical benefit (71%; 3 complete responses, 1 partial response, 1 stable disease). These included 2 dogs with durable responses after toceranib discontinuation. Median progression‐free interval (PFI) in dogs with gross disease was 110 weeks (range, 36‐155 weeks). Median PFI in dogs with microscopic disease was 67 weeks (range, 9‐257 weeks). Metastasis at diagnosis (P = 0.04) and high mitotic index (P < 0.001) were associated with shorter PFI in toceranib‐treated dogs.Conclusions and Clinical ImportanceBiological activity of toceranib is evident in dogs with gross disease. Metastasis of GIST at diagnosis, as well as high tumor mitotic index, was associated with shorter PFI in toceranib‐treated dogs. Larger studies are needed to define postsurgical risk and refine the use of toceranib in dogs with gross and microscopic GIST.

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Section: Discussionmentioning

confidence: 99%

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs

Berger

Johannes

Jergens

et al. 2018

Veterinary Internal Medicne

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“…Sheehan et al [7] described for the first time the expression of COX-2 in GISTs, and demonstrated COX-2 protein expression in 12 of 15 (80%) of the tumors. Stewart et al [20] showed COX-2 protein expression in 35 of 38 (92%) GISTs and indicated that COX-2 may be useful as an additional molecular marker to aid in the identification of GIST, particularly in those cases with epithelioid histology or where KIT is only weakly or focally positive. Epidemiologic data suggest that the treatment with aspirin and NSAIDs prevents colorectal cancer and reduces the size and number of corectal polyps [21,22] .…”

Section: Discussionmentioning

confidence: 99%

Expression of COX-2, PCNA, Ki-67 and p53 in gastrointestinal stromal tumors and its relationship with histopathological parameters

Gümürdülü

Erdoğan²,

Kayaselçuk³

et al. 2007

WJG

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AIM:To investigate the expression of Cyclooxygenase-2 (COX-2), proliferating cell nuclear antigen (PCNA), Ki-67 and p53 in gastrointestinal stromal tumors (GISTs) and its relationship with histopathological parameters. METHODS:Twenty-five GISTs were examined by light microscopy and immunohistochemistry. c-kit, CD34, SMA, S-100 protein, COX-2, PCNA, Ki-67 and p53 were detected immunohistochemically and the relationship was evaluated among histopathologic parameters such as mitotic index (MI), tumor grade, tumor size, COX-2, PCNA, Ki-67 and p53.RESULTS: COX-2 protein expression was found in 19 of 25 (76%) of the tumors, and expression was noted in the cytoplasm of the tumor cells. p53 was significantly related to MI and tumor grade but no relationship was found between COX-2, proliferation markers and MI, tumor grade and tumor size. CONCLUSION: COX-2 is expressed in most GISTsand it may play an important role in the proliferation and progression of these tumors or a useful marker to identify GIST. Although immunohistochemical assessment of p53 can be used for distinguishing the risk groups of GISTs, tumor size and mitotic rate should be considered at the same time.

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“…Based on the data obtained, authors reported that COX-2 inhibitors could be beneficial in GIST although these tumors are not responsive to chemotherapy and radiotherapy, and partial response to tyrosine kinase inhibitors is obtained. In the trial by Stewart et al, a higher tumor recurrence and/or death was observed in the group with a low or limited COX-2 expression, as well as the COX-2 positiveness in 92% of the cases; however no statistical difference was detected (Stewart et al, 2006).…”

Section: Discussionmentioning

confidence: 89%

“…COX-2 inhibitors are established. The relation of COX-2 expression and GIST is a very new investigational subject, and there are limited trials on this subject (Sheehan et al, 2003, Stewart et al, 2006, Stepanova et al, 2005Gumurdulu et al, 2007). There are many trials on prognosis and survival analysis investigating COX-2 expression in various cancer types, and primarily colon cancer; however, conduct of trials on prognosis and survival analysis in GIST is difficult since such tumors are relatively rare.…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2 expression in gastrointestinal stromal tumours

Sevinç

Camcı²,

Sarı³

et al. 2008

JCO

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Background: While it is well known that cyclooxygenase-2 (COX-2) expression is increased in colorectal adenoma and carcinoma, there is only limited information on its status in stromal tumours. Methods: Immunohistochemical COX-2 staining was performed on a total of 42 confirmed gastrointestinal stromal tumours (GISTs) in the Pathology Department of Gaziantep University and the findings were compared with various other parameters. Results: We found a statistically significant correlation between the tumor mitosis and COX-2 expression in GISTs. However, there was no relationship between COX-2 expression and death rate, presence of metastasis, tumour size, risk staging, usage of tyrosine kinase inhibitors, and complete resection rate. Conclusions: In the light of these findings, the usage of COX-2 inhibitors with or without tyrosine kinase inhibitors in GIST patients may be helpful in the adjuvant setting to prevent or delay recurrence. Moreover, we need more studies to define the status of COX-2 inhibitors in GISTs.

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Cyclooxygenase-2 Expression and Clinical Outcome in Gastrointestinal Stromal Tumors

Cited by 6 publications

References 23 publications

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs

Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of gastrointestinal stromal tumors of dogs

Expression of COX-2, PCNA, Ki-67 and p53 in gastrointestinal stromal tumors and its relationship with histopathological parameters

Cyclooxygenase-2 expression in gastrointestinal stromal tumours

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