Limits...
Correlation between ERK1 and STAT3 expression and chemoresistance in patients with conventional osteosarcoma.

Salas S, Jiguet-Jiglaire C, Campion L, Bartoli C, Frassineti F, Deville JL, Maues De Paula A, Forest F, Jézéquel P, Gentet JC, Bouvier C - BMC Cancer (2014)

Bottom Line: Expression of selected relevant genes identified by SSH was validated by using QRT-PCR.ERK1 and STAT3 mRNA level were significantly different between PR and GR in an independent cohort.Our results suggest that ERK1 and STAT3 expression are good predictive markers for chemotherapy response and that inhibitors might be used in combination with common chemotherapeutic drugs in conventional osteosarcomas.

View Article: PubMed Central - PubMed

Affiliation: Aix Marseille Univ, CRO2, 13284 Marseille, France. sebastien.salas@ap-hm.fr.

ABSTRACT

Background: The standard therapy regimen of conventional osteosarcoma includes neoadjuvant chemotherapy followed by surgical resection and postoperative chemotherapy. The percentage of necrotic tissue following induction chemotherapy is assessed by using the Huvos grading system, which classifies patients as "poor responders" (PR) and "good responders" (GR). The aim of this study was to identify molecular markers expressed differentially between good and poor responders to neoadjuvant chemotherapy in order to predict the response to chemotherapy in conventional osteosarcomas before beginning treatment.

Methods: Suppression Substractive Hybridization (SSH) was performed by using cDNA from frozen biopsy specimens. Expression of selected relevant genes identified by SSH was validated by using QRT-PCR. Immunohistochemistry (IHC) on tissue microarray (TMA) sections of 52 biopsies was performed to investigate protein expression in an independent cohort.

Results: ERK1 and STAT3 mRNA level were significantly different between PR and GR in an independent cohort. Phosphorylated STAT3 and ERK1 expressions by IHC on TMA were correlated with poor response to chemotherapy.

Conclusions: Our results suggest that ERK1 and STAT3 expression are good predictive markers for chemotherapy response and that inhibitors might be used in combination with common chemotherapeutic drugs in conventional osteosarcomas.

Show MeSH

Related in: MedlinePlus

IHC pSTAT3 scores. Score 0: negative staining (X200). Score 1: >50% of nuclei are labeled with low staining intensity (X200). Score 2: <50% cells with moderate staining intensity and <25% of cells are highly stained (X200). Score 3: more than 50% of nuclei are stained with moderate staining intensity (X200).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4150966&req=5

Fig2: IHC pSTAT3 scores. Score 0: negative staining (X200). Score 1: >50% of nuclei are labeled with low staining intensity (X200). Score 2: <50% cells with moderate staining intensity and <25% of cells are highly stained (X200). Score 3: more than 50% of nuclei are stained with moderate staining intensity (X200).

Mentions: pSTAT3 nuclear expression was examined in 45 cases out of 52 and a high score was observed in 20 cases (score 2 and 3). pERK1 expression was examined in 45 cases out of 52 (low score in 25 cases and high score in 20 cases) (Figure 2). pSTAT3 protein expression was correlated to poor response to chemotherapy for a percentage of viable residual cells ≤10%, with the higher scores in the PR group (p = 0.036). A statistically significant correlation was also found between pERK1 protein expression and response to chemotherapy when comparing low scores (0-1) versus high scores (2-3) (p = 0.007). Moreover, the correlation between the expression of pSTAT3 and pERK1 in IHC and the response to chemotherapy remained statistically significant for patients under 25 years (p = 0.024 and p = 0.010 respectively). For a percentage of viable residual cells lower than 5%, a statistically significant correlation was still found between pSTAT3 or pERK1 protein expression and response to chemotherapy (p = 0.013 and p = 0.035 respectively). Whatever the threshold (5 or 10%), positive predictive value (probability of belonging to the group of PR in case of high score) of both pSTAT3 and pERK1 in combination was 91%. Negative predictive value (probability of belonging to the group of GR in case of low score) of both pSTAT3 and pERK1 in combination for a 5 and 10% threshold were 69% and 75% respectivelyTable 5


Correlation between ERK1 and STAT3 expression and chemoresistance in patients with conventional osteosarcoma.

Salas S, Jiguet-Jiglaire C, Campion L, Bartoli C, Frassineti F, Deville JL, Maues De Paula A, Forest F, Jézéquel P, Gentet JC, Bouvier C - BMC Cancer (2014)

IHC pSTAT3 scores. Score 0: negative staining (X200). Score 1: >50% of nuclei are labeled with low staining intensity (X200). Score 2: <50% cells with moderate staining intensity and <25% of cells are highly stained (X200). Score 3: more than 50% of nuclei are stained with moderate staining intensity (X200).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4150966&req=5

Fig2: IHC pSTAT3 scores. Score 0: negative staining (X200). Score 1: >50% of nuclei are labeled with low staining intensity (X200). Score 2: <50% cells with moderate staining intensity and <25% of cells are highly stained (X200). Score 3: more than 50% of nuclei are stained with moderate staining intensity (X200).
Mentions: pSTAT3 nuclear expression was examined in 45 cases out of 52 and a high score was observed in 20 cases (score 2 and 3). pERK1 expression was examined in 45 cases out of 52 (low score in 25 cases and high score in 20 cases) (Figure 2). pSTAT3 protein expression was correlated to poor response to chemotherapy for a percentage of viable residual cells ≤10%, with the higher scores in the PR group (p = 0.036). A statistically significant correlation was also found between pERK1 protein expression and response to chemotherapy when comparing low scores (0-1) versus high scores (2-3) (p = 0.007). Moreover, the correlation between the expression of pSTAT3 and pERK1 in IHC and the response to chemotherapy remained statistically significant for patients under 25 years (p = 0.024 and p = 0.010 respectively). For a percentage of viable residual cells lower than 5%, a statistically significant correlation was still found between pSTAT3 or pERK1 protein expression and response to chemotherapy (p = 0.013 and p = 0.035 respectively). Whatever the threshold (5 or 10%), positive predictive value (probability of belonging to the group of PR in case of high score) of both pSTAT3 and pERK1 in combination was 91%. Negative predictive value (probability of belonging to the group of GR in case of low score) of both pSTAT3 and pERK1 in combination for a 5 and 10% threshold were 69% and 75% respectivelyTable 5

Bottom Line: Expression of selected relevant genes identified by SSH was validated by using QRT-PCR.ERK1 and STAT3 mRNA level were significantly different between PR and GR in an independent cohort.Our results suggest that ERK1 and STAT3 expression are good predictive markers for chemotherapy response and that inhibitors might be used in combination with common chemotherapeutic drugs in conventional osteosarcomas.

View Article: PubMed Central - PubMed

Affiliation: Aix Marseille Univ, CRO2, 13284 Marseille, France. sebastien.salas@ap-hm.fr.

ABSTRACT

Background: The standard therapy regimen of conventional osteosarcoma includes neoadjuvant chemotherapy followed by surgical resection and postoperative chemotherapy. The percentage of necrotic tissue following induction chemotherapy is assessed by using the Huvos grading system, which classifies patients as "poor responders" (PR) and "good responders" (GR). The aim of this study was to identify molecular markers expressed differentially between good and poor responders to neoadjuvant chemotherapy in order to predict the response to chemotherapy in conventional osteosarcomas before beginning treatment.

Methods: Suppression Substractive Hybridization (SSH) was performed by using cDNA from frozen biopsy specimens. Expression of selected relevant genes identified by SSH was validated by using QRT-PCR. Immunohistochemistry (IHC) on tissue microarray (TMA) sections of 52 biopsies was performed to investigate protein expression in an independent cohort.

Results: ERK1 and STAT3 mRNA level were significantly different between PR and GR in an independent cohort. Phosphorylated STAT3 and ERK1 expressions by IHC on TMA were correlated with poor response to chemotherapy.

Conclusions: Our results suggest that ERK1 and STAT3 expression are good predictive markers for chemotherapy response and that inhibitors might be used in combination with common chemotherapeutic drugs in conventional osteosarcomas.

Show MeSH
Related in: MedlinePlus