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Cyclooxygenase 2 (COX2) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Are Stage-Dependent Prognostic Markers of Malignant Melanoma.

Meyer S, Vogt T, Landthaler M, Berand A, Reichle A, Bataille F, Marx AH, Menz A, Hartmann A, Kunz-Schughart LA, Wild PJ - PPAR Res (2009)

Bottom Line: Using tissue microarrays (TMAs) we studied COX2/PPARG immunoreactivity in a broad spectrum of tumors focussing on clinicopathological correlations and the outcome of patients with malignant melanoma (MM).Regarding primary MM, COX2 expression indicates an increased risk of tumor recurrence.In metastatic MM, PPARG expression may be a predicitive marker for response to biomodulatory stroma-targeted therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of Regensburg, 93042 Regensburg, Germany.

ABSTRACT
Using tissue microarrays (TMAs) we studied COX2/PPARG immunoreactivity in a broad spectrum of tumors focussing on clinicopathological correlations and the outcome of patients with malignant melanoma (MM). TMA-1 contained normal and tumor tissues (n = 3448) from 47 organs including skin neoplasms (n = 323); TMA-2 88 primary MM, 101 metastases, and 161 benign nevi. Based on a biomodulatory approach combining COX/PPAR-targeting with metronomic low-dose chemotherapy metastases of 36 patients participating in a randomized trial with metastatic (stage IV) melanoma were investigated using TMA-3. COX2/PPARG immunoreactivity significantly increased from nevi to primary MM and metastases; COX2 positivity was associated with advanced Clark levels and shorter recurrence-free survival. Patients with PPARG-positive metastases and biomodulatory metronomic chemotherapy alone or combined with COX2/PPARG-targeting showed a significantly prolonged progression-free survival. Regarding primary MM, COX2 expression indicates an increased risk of tumor recurrence. In metastatic MM, PPARG expression may be a predicitive marker for response to biomodulatory stroma-targeted therapy.

No MeSH data available.


Related in: MedlinePlus

Distribution of time (months) to death and tumor progression among patients with advanced metastatic melanomas in correlation with immunoreactivity of PPARG (a), (b) or COX2 (c), (d). All patients received biomodulatory treatment. The calculation was performed according to the method of Kaplan and Meier.
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fig4: Distribution of time (months) to death and tumor progression among patients with advanced metastatic melanomas in correlation with immunoreactivity of PPARG (a), (b) or COX2 (c), (d). All patients received biomodulatory treatment. The calculation was performed according to the method of Kaplan and Meier.

Mentions: Considering all 36 patients receiving biomodulatory therapy expression of PPARG (score 1+-3+) in the metastases was significantly associated with longer progression-free survival (P = .044) but not with overall survival (P = .179; Figures 4(a) and 4(b)). Expression of COX2 (score 2+-3+) in the metastases, however, was not associated with overall and progression-free survival, respectively (Figures 4(c) and 4(d)). Besides PPARG immunoreactivity, stage of the primary melanoma was also a significant prognostic factor for progression-free survival (P = .016; Table 4). In a multivariate Cox regression model, using primary tumor stage (pTis-pT3 versus pT4) and PPARG expression (negative versus positive) as covariates, neither PPARG immunoreactivity nor primary tumor stage remained significant (data not shown).


Cyclooxygenase 2 (COX2) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Are Stage-Dependent Prognostic Markers of Malignant Melanoma.

Meyer S, Vogt T, Landthaler M, Berand A, Reichle A, Bataille F, Marx AH, Menz A, Hartmann A, Kunz-Schughart LA, Wild PJ - PPAR Res (2009)

Distribution of time (months) to death and tumor progression among patients with advanced metastatic melanomas in correlation with immunoreactivity of PPARG (a), (b) or COX2 (c), (d). All patients received biomodulatory treatment. The calculation was performed according to the method of Kaplan and Meier.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2712952&req=5

fig4: Distribution of time (months) to death and tumor progression among patients with advanced metastatic melanomas in correlation with immunoreactivity of PPARG (a), (b) or COX2 (c), (d). All patients received biomodulatory treatment. The calculation was performed according to the method of Kaplan and Meier.
Mentions: Considering all 36 patients receiving biomodulatory therapy expression of PPARG (score 1+-3+) in the metastases was significantly associated with longer progression-free survival (P = .044) but not with overall survival (P = .179; Figures 4(a) and 4(b)). Expression of COX2 (score 2+-3+) in the metastases, however, was not associated with overall and progression-free survival, respectively (Figures 4(c) and 4(d)). Besides PPARG immunoreactivity, stage of the primary melanoma was also a significant prognostic factor for progression-free survival (P = .016; Table 4). In a multivariate Cox regression model, using primary tumor stage (pTis-pT3 versus pT4) and PPARG expression (negative versus positive) as covariates, neither PPARG immunoreactivity nor primary tumor stage remained significant (data not shown).

Bottom Line: Using tissue microarrays (TMAs) we studied COX2/PPARG immunoreactivity in a broad spectrum of tumors focussing on clinicopathological correlations and the outcome of patients with malignant melanoma (MM).Regarding primary MM, COX2 expression indicates an increased risk of tumor recurrence.In metastatic MM, PPARG expression may be a predicitive marker for response to biomodulatory stroma-targeted therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University of Regensburg, 93042 Regensburg, Germany.

ABSTRACT
Using tissue microarrays (TMAs) we studied COX2/PPARG immunoreactivity in a broad spectrum of tumors focussing on clinicopathological correlations and the outcome of patients with malignant melanoma (MM). TMA-1 contained normal and tumor tissues (n = 3448) from 47 organs including skin neoplasms (n = 323); TMA-2 88 primary MM, 101 metastases, and 161 benign nevi. Based on a biomodulatory approach combining COX/PPAR-targeting with metronomic low-dose chemotherapy metastases of 36 patients participating in a randomized trial with metastatic (stage IV) melanoma were investigated using TMA-3. COX2/PPARG immunoreactivity significantly increased from nevi to primary MM and metastases; COX2 positivity was associated with advanced Clark levels and shorter recurrence-free survival. Patients with PPARG-positive metastases and biomodulatory metronomic chemotherapy alone or combined with COX2/PPARG-targeting showed a significantly prolonged progression-free survival. Regarding primary MM, COX2 expression indicates an increased risk of tumor recurrence. In metastatic MM, PPARG expression may be a predicitive marker for response to biomodulatory stroma-targeted therapy.

No MeSH data available.


Related in: MedlinePlus