Limits...
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 chemotherapy. Survival of patients under chemotherapy, 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 treated (gray markers) or not treated (black markers) with chemotherapy 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
getmorefigures.php?uid=PMC4940753&req=5

Fig2: Kaplan-Meier survival curves for patients undergoing chemotherapy. Survival of patients under chemotherapy, 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 treated (gray markers) or not treated (black markers) with chemotherapy is displayed (bottom panel). The x-axis indicates years since diagnosis, the y-axis reflects % surviving patients

Mentions: For the analysis of chemotherapy responses, the comparison to the non-chemotherapy treated group was not meaningful, because the survival of the treated group was lower, which is not reflecting harm caused by the treatment but indicates the circumstance that chemotherapy was given to patients with aggressive tumors and poor prognoses. The survival curves of patients undergoing chemotherapy (Fig. 2), when distinguished according to low (0–1) versus high (2–3) immunohistochemical markers, confirm the poor survival prognosis associated with exon 4 and osteopontin-c [8], particularly reflected in a higher rate of patient deaths between 2 and 6 years after diagnosis in the high intensity group of each marker. Of note, the survival difference between exon 4 high and low appeared to be larger than between osteopontin-c high and low, implying the possibility that the marker could also be predictive of a poor chemotherapy response.Fig. 2


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 chemotherapy. Survival of patients under chemotherapy, 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 treated (gray markers) or not treated (black markers) with chemotherapy 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

Fig2: Kaplan-Meier survival curves for patients undergoing chemotherapy. Survival of patients under chemotherapy, 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 treated (gray markers) or not treated (black markers) with chemotherapy is displayed (bottom panel). The x-axis indicates years since diagnosis, the y-axis reflects % surviving patients
Mentions: For the analysis of chemotherapy responses, the comparison to the non-chemotherapy treated group was not meaningful, because the survival of the treated group was lower, which is not reflecting harm caused by the treatment but indicates the circumstance that chemotherapy was given to patients with aggressive tumors and poor prognoses. The survival curves of patients undergoing chemotherapy (Fig. 2), when distinguished according to low (0–1) versus high (2–3) immunohistochemical markers, confirm the poor survival prognosis associated with exon 4 and osteopontin-c [8], particularly reflected in a higher rate of patient deaths between 2 and 6 years after diagnosis in the high intensity group of each marker. Of note, the survival difference between exon 4 high and low appeared to be larger than between osteopontin-c high and low, implying the possibility that the marker could also be predictive of a poor chemotherapy response.Fig. 2

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