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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

Immunohistochemical COX2 and PPARG staining of malignant melanomas on TMA-2. Original magnification 10x (insets 200x). Representative examples of a primary malignant melanoma with negative (a) and strong (b) immunoreactivity for COX2. Representative examples of a primary malignant melanoma with negative (c) and strong (d) immunoreactivity for PPARG.
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fig1: Immunohistochemical COX2 and PPARG staining of malignant melanomas on TMA-2. Original magnification 10x (insets 200x). Representative examples of a primary malignant melanoma with negative (a) and strong (b) immunoreactivity for COX2. Representative examples of a primary malignant melanoma with negative (c) and strong (d) immunoreactivity for PPARG.

Mentions: Based on the results of TMA-1, a second TMA (TMA-2) with clinical follow-up data sampling primary malignant melanomas and melanoma metastases as well as benign nevi was constructed. COX2 and PPARG immunoreactivity was informative in 86.0% (301/350) and 91.7% (321/350) of cases, respectively. Expression of COX2 and PPARG of any intensity was detected in 73.8% (222/301) and in 15.0% (48/321) of informative cases. Representative negative and positive COX2 and PPARG immunostaining patterns in malignant melanoma are shown in Figures 1(a)–1(d). Figures 2(a) and 2(b) summarize the results of COX2 and PPARG IHC for primary melanomas, metastases, and nevi on TMA-2. The percentage of COX2 positive cases significantly increased from benign nevi (51%) to primary melanomas (86%) and melanoma metastases (91%; P < .001; Figure 2(a)). Likewise, PPARG immunoreactivity significantly increased from benign nevi (0%) to malignant melanomas (22%) and melanoma metastases (33%; P < .001; Figure 2(b)). Clinicopathologic variables of melanoma patients were correlated with COX2 and PPARG expression (Table 2). In primary melanomas, positive COX2 immunoreactivity was significantly related to advanced Clark levels (P = .004), but no other clinicopathologic variables such as tumor growth pattern, p53 immunoreactivity, and Ki-67 labeling index. Skin metastases demonstrated a gradually weaker COX2 immunoreactivity compared with lymph node metastases (P = .013). Among the various types of benign nevi on TMA-2, COX2 expression was significantly increased in congential nevi compared to compound, junctional, and dermal melanocytic nevi (P < .001).


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)

Immunohistochemical COX2 and PPARG staining of malignant melanomas on TMA-2. Original magnification 10x (insets 200x). Representative examples of a primary malignant melanoma with negative (a) and strong (b) immunoreactivity for COX2. Representative examples of a primary malignant melanoma with negative (c) and strong (d) immunoreactivity for PPARG.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2712952&req=5

fig1: Immunohistochemical COX2 and PPARG staining of malignant melanomas on TMA-2. Original magnification 10x (insets 200x). Representative examples of a primary malignant melanoma with negative (a) and strong (b) immunoreactivity for COX2. Representative examples of a primary malignant melanoma with negative (c) and strong (d) immunoreactivity for PPARG.
Mentions: Based on the results of TMA-1, a second TMA (TMA-2) with clinical follow-up data sampling primary malignant melanomas and melanoma metastases as well as benign nevi was constructed. COX2 and PPARG immunoreactivity was informative in 86.0% (301/350) and 91.7% (321/350) of cases, respectively. Expression of COX2 and PPARG of any intensity was detected in 73.8% (222/301) and in 15.0% (48/321) of informative cases. Representative negative and positive COX2 and PPARG immunostaining patterns in malignant melanoma are shown in Figures 1(a)–1(d). Figures 2(a) and 2(b) summarize the results of COX2 and PPARG IHC for primary melanomas, metastases, and nevi on TMA-2. The percentage of COX2 positive cases significantly increased from benign nevi (51%) to primary melanomas (86%) and melanoma metastases (91%; P < .001; Figure 2(a)). Likewise, PPARG immunoreactivity significantly increased from benign nevi (0%) to malignant melanomas (22%) and melanoma metastases (33%; P < .001; Figure 2(b)). Clinicopathologic variables of melanoma patients were correlated with COX2 and PPARG expression (Table 2). In primary melanomas, positive COX2 immunoreactivity was significantly related to advanced Clark levels (P = .004), but no other clinicopathologic variables such as tumor growth pattern, p53 immunoreactivity, and Ki-67 labeling index. Skin metastases demonstrated a gradually weaker COX2 immunoreactivity compared with lymph node metastases (P = .013). Among the various types of benign nevi on TMA-2, COX2 expression was significantly increased in congential nevi compared to compound, junctional, and dermal melanocytic nevi (P < .001).

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