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Osteopontin splice variants are differential predictors of breast cancer treatment responses.

Zduniak K, Agrawal A, Agrawal S, Hossain MM, Ziolkowski P, Weber GF - BMC Cancer (2016)

Bottom Line: It is not known which splice variants may mediate treatment resistance.We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil).Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Wroclaw Medical University, Wroclaw, Poland.

ABSTRACT

Background: Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance.

Methods: Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses in 119 Polish breast cancer patients who presented between 1995 and 2008.

Results: We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment.

Conclusions: The addition of osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier survival curves for patients undergoing radiotherapy. Survival of patients under radiotherapy, distinguished according to low (0–1, diamonds) versus high (2–3, triangles) immunohistochemical markers. Shown are Kaplan Meier curves for osteopontin-c (top panel) or exon 4 (middle panel). For comparison, the survival of all patients receiving radiation (gray markers) or not treated with radiation (black markers) is displayed (bottom panel). The x-axis indicates years since diagnosis, the y-axis reflects % surviving patients
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Fig3: Kaplan-Meier survival curves for patients undergoing radiotherapy. Survival of patients under radiotherapy, distinguished according to low (0–1, diamonds) versus high (2–3, triangles) immunohistochemical markers. Shown are Kaplan Meier curves for osteopontin-c (top panel) or exon 4 (middle panel). For comparison, the survival of all patients receiving radiation (gray markers) or not treated with radiation (black markers) is displayed (bottom panel). The x-axis indicates years since diagnosis, the y-axis reflects % surviving patients

Mentions: The Kaplan Meier survival curves of patients undergoing radiation treatment, distinguished according to low (0–1) versus high (2–3) immunohistochemical markers, again confirm the poor survival associated with exon 4 and osteopontin-c. Although the curves converge after about 10 years, during 2–6 years substantially more patients die in the high marker intensity groups than in the low marker intensity groups (Fig. 3).Fig. 3


Osteopontin splice variants are differential predictors of breast cancer treatment responses.

Zduniak K, Agrawal A, Agrawal S, Hossain MM, Ziolkowski P, Weber GF - BMC Cancer (2016)

Kaplan-Meier survival curves for patients undergoing radiotherapy. Survival of patients under radiotherapy, distinguished according to low (0–1, diamonds) versus high (2–3, triangles) immunohistochemical markers. Shown are Kaplan Meier curves for osteopontin-c (top panel) or exon 4 (middle panel). For comparison, the survival of all patients receiving radiation (gray markers) or not treated with radiation (black markers) is displayed (bottom panel). The x-axis indicates years since diagnosis, the y-axis reflects % surviving patients
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940753&req=5

Fig3: Kaplan-Meier survival curves for patients undergoing radiotherapy. Survival of patients under radiotherapy, distinguished according to low (0–1, diamonds) versus high (2–3, triangles) immunohistochemical markers. Shown are Kaplan Meier curves for osteopontin-c (top panel) or exon 4 (middle panel). For comparison, the survival of all patients receiving radiation (gray markers) or not treated with radiation (black markers) is displayed (bottom panel). The x-axis indicates years since diagnosis, the y-axis reflects % surviving patients
Mentions: The Kaplan Meier survival curves of patients undergoing radiation treatment, distinguished according to low (0–1) versus high (2–3) immunohistochemical markers, again confirm the poor survival associated with exon 4 and osteopontin-c. Although the curves converge after about 10 years, during 2–6 years substantially more patients die in the high marker intensity groups than in the low marker intensity groups (Fig. 3).Fig. 3

Bottom Line: It is not known which splice variants may mediate treatment resistance.We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil).Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Wroclaw Medical University, Wroclaw, Poland.

ABSTRACT

Background: Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance.

Methods: Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses in 119 Polish breast cancer patients who presented between 1995 and 2008.

Results: We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment.

Conclusions: The addition of osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment.

No MeSH data available.


Related in: MedlinePlus