GIST with a Twist—Upregulation of PDGF-B Resulting in Metachronous Gastrointestinal Stromal Tumor and Dermatofibrosarcoma Protuberans

McCarthy, Colin J.; O’Brien, G. C.; Cummins, Robert; Kay, Elaine W.; Broe, Patrick J.

doi:10.1007/s11605-009-1088-z

Cited by 5 publications

(8 citation statements)

References 20 publications

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“…This finding suggests that tyrosine kinase receptor blockade may represent a promising therapy to control canine PWT recurrence. If this hypothesis is substantiated by future clinical studies, results could parallel observations reported for some human STS subtypes 9,10,32 and in a few studies in veterinary medicine that attempted target therapies toward specific GFs. 27,31,37 Noteworthy, the efficacy and safety of the use of a commercially available tyrosine kinase inhibitor for canine mast cell tumor therapy has been already reported.…”

Section: Discussionsupporting

confidence: 64%

“…Interestingly, PWT neoplastic MCs highly expressed PDGFRb and PDGFB, suggesting the presence of an additional autocrine and paracrine pathway involved in PWT development and growth, characterized by aberrant expression of PDGFB. Upregulation of the PDGFB pathway has been demonstrated in canine hemangiosarcoma, feline injection site sarcoma, 3,28 and human sarcomas, 32 in which it has been also targeted for therapeutic purposes. 9,12 The bFGF-Flg pathway was also highly expressed by canine PWTs.…”

Section: Discussionmentioning

confidence: 99%

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Growth Factors and COX2 Expression in Canine Perivascular Wall Tumors

et al. 2015

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Canine perivascular wall tumors (PWTs) are a group of subcutaneous soft tissue sarcomas developing from vascular mural cells. Mural cells are involved in angiogenesis through a complex crosstalk with endothelial cells mediated by several growth factors and their receptors. The evaluation of their expression may have relevance since they may represent a therapeutic target in the control of canine PWTs. The expression of vascular endothelial growth factor (VEGF) and receptors VEGFR-I/II, basic fibroblast growth factor (bFGF) and receptor Flg, platelet-derived growth factor B (PDGFB) and receptor PDGFRb, transforming growth factor b1 (TGFb1) and receptors TGFbR-I/II, and cyclooxygenase 2 (COX2) was evaluated on frozen sections of 40 PWTs by immunohistochemistry and semiquantitatively scored to identify their potential role in PWT development. Statistical analysis was performed to analyze possible correlations between Ki67 labeling index and the expression of each molecule. Proteins of the VEGF-, PDGFB-, and bFGF-mediated pathways were highly expressed in 27 (67.5%), 30 (75%), and 19 (47.5%) of 40 PWTs, respectively. Proteins of the TGFb1-and COX2-mediated pathways were highly expressed in 4 (10%) and 14 (35%) of 40 cases. Statistical analysis identified an association between VEGF and VEGFR-I/II (P ¼ .015 and .003, respectively), bFGF and Flg (P ¼ .038), bFGF and PDGFRb (P ¼ .003), and between TGFb1 and COX2 (P ¼ .006). These findings were consistent with the mechanisms that have been reported to play a role in angiogenesis and in tumor development. No association with Ki67 labeling index was found. VEGF-, PDGFB-, and bFGF-mediated pathways seem to have a key role in PWT development and growth. Blockade of tyrosine kinase receptors after surgery could represent a promising therapy with the aim to reduce the PWT relapse rate and prolong the time to relapse.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Growth Factors and COX2 Expression in Canine Perivascular Wall Tumors

et al. 2015

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“…There have been many reports of additional malignancies in patients diagnosed with a GIST. However, it is unclear whether this represents a coincidental finding, improved detection or surveillance bias or whether a potential causal association exists . Similarly, it is difficult to ascertain whether the apparent reported higher risk of additional malignancies is related to cancers present at the index diagnosis of a GIST or those developing at a later time point.…”

Section: Discussionmentioning

confidence: 99%

“…They confirmed the rarity of GIST, estimating the age‐adjusted incidence at 0.68/100,000 . Despite its rarity, an interesting anecdotal observation amongst those who treat GIST is the apparent high rate of additional malignancies following the diagnosis of GIST . Agaimy et al .…”

mentioning

confidence: 87%

“…5 Despite its rarity, an interesting anecdotal observation amongst those who treat GIST is the apparent high rate of additional malignancies following the diagnosis of GIST. [6][7][8] Agaimy et al have reported a range incidence of additional malignancies in GIST of 4.5-33%, with a mean of 13% in their review of the literature, mirroring a 13.4% rate of additional malignancies in their institutional series. 9 In a more recent population-based study, Murphy et al reported a 17.1% rate of additional malignancies and an increased risk of additional malignancies compared to the general population before and after a GIST diagnosis of 44 and 66%, respectively.…”

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confidence: 99%

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The impact of additional malignancies in patients diagnosed with gastrointestinal stromal tumors

Smith

Mahar

et al. 2016

Intl Journal of Cancer

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A higher incidence of additional malignancies has been described in patients diagnosed with gastrointestinal stromal tumors (GIST). This study aimed to identify risk factors for developing additional malignancies in patients diagnosed with GIST and evaluate the impact on survival. Individuals diagnosed with GIST from 2001 to2009 were identified from the SEER database. Logistic regression was used to identify predictors of additional malignancies and Cox‐proportional hazards regression used to identify predictors of survival. In the study period, 1705 cases of GIST were identified, with 181 (10.6%) patients developing additional malignancies. Colorectal cancer was the most common cancer developing within 6 months of GIST diagnosis (30%). The median time to diagnosis of a malignancy after 6 months of GIST diagnosis was 21.9 months. Older age (p < 0.0001) and extraoesophagogastric GIST (p = 0.0027) were significant prognostic factors associated with additional malignancies. The overall 5‐year survival was 65%, with the presence of additional malignancies within 6 months of GIST diagnosis associated with poor overall survival (54%, HR 1.55 1.05–2.3 95% CI, p = 0.04). Predictive factors of additional malignancies in patients diagnosed with GIST are increasing age and the primary disease site. Developing additional malignancies within 6 months of GIST diagnosis is associated with poorer overall survival. Targeted surveillance may be warranted in patients diagnosed with GIST that are at high risk of developing additional malignancies.

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Tyrosine Kinase Receptor Expression in Canine Liposarcoma

et al. 2016

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The expression of tyrosine kinase receptors is attracting major interest in human and veterinary oncological pathology because of their role as targets for adjuvant therapies. Little is known about tyrosine kinase receptor (TKR) expression in canine liposarcoma (LP), a soft tissue sarcoma. The aim of this study was to evaluate the immunohistochemical expression of the TKRs fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptor-β (PDGFRβ); their ligands, fibroblast growth factor 2 (FGF2) and platelet-derived growth factor B (PDGFB); and c-kit in canine LP. Immunohistochemical labeling was categorized as high or low expression and compared with the mitotic count and MIB-1-based proliferation index. Fifty canine LPs were examined, classified, and graded. Fourteen cases were classified as well differentiated, 7 as myxoid, 25 as pleomorphic, and 4 as dedifferentiated. Seventeen cases were grade 1, 26 were grade 2, and 7 were grade 3. A high expression of FGF2, FGFR1, PDGFB, and PDGFRβ was identified in 62% (31/50), 68% (34/50), 81.6% (40/49), and 70.8% (34/48) of the cases, respectively. c-kit was expressed in 12.5% (6/48) of the cases. Mitotic count negatively correlated with FGF2 ( R = -0.41; P < .01), being lower in cases with high FGF2 expression, and positively correlated with PDGFRβ ( R = 0.33; P < .01), being higher in cases with high PDGFRβ expression. No other statistically significant correlations were identified. These results suggest that the PDGFRβ-mediated pathway may have a role in the progression of canine LP and may thus represent a promising target for adjuvant cancer therapies.

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GIST with a Twist—Upregulation of PDGF-B Resulting in Metachronous Gastrointestinal Stromal Tumor and Dermatofibrosarcoma Protuberans

Cited by 5 publications

References 20 publications

Growth Factors and COX2 Expression in Canine Perivascular Wall Tumors

Growth Factors and COX2 Expression in Canine Perivascular Wall Tumors

The impact of additional malignancies in patients diagnosed with gastrointestinal stromal tumors

Tyrosine Kinase Receptor Expression in Canine Liposarcoma

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