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Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients.

Park SH, Noh SJ, Kim KM, Bae JS, Kwon KS, Jung SH, Kim JR, Lee H, Chung MJ, Moon WS, Kang MJ, Jang KY - Transl Oncol (2015)

Bottom Line: In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph) was an additional independent prognostic predictor for OS (P < .001) and RFS (P < .001).The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1) subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4) subgroup.This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents.

View Article: PubMed Central - PubMed

Affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA, USA.

No MeSH data available.


Related in: MedlinePlus

Prognostic significance of the combined expression pattern of PARP1, γH2AX, BRCA1, and BRCA2 in 192 BCAs. Kaplan-Meier survival analysis for OS (A) and RFS (B) between the subgroups classified according to CSbbph. CSbbph was established with the sum of positivity of BRCA1, BRCA2, PARP1, and γH2AX (negative, 0; positive, 1). CSbbph scores were grouped as CSbbph-low (CSbbph 0-1), CSbbph-intermediate (CSbbph 2-3), and CSbbph-high (CSbbph 4); 10y-RFS, RFS rate at 10years.
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f0015: Prognostic significance of the combined expression pattern of PARP1, γH2AX, BRCA1, and BRCA2 in 192 BCAs. Kaplan-Meier survival analysis for OS (A) and RFS (B) between the subgroups classified according to CSbbph. CSbbph was established with the sum of positivity of BRCA1, BRCA2, PARP1, and γH2AX (negative, 0; positive, 1). CSbbph scores were grouped as CSbbph-low (CSbbph 0-1), CSbbph-intermediate (CSbbph 2-3), and CSbbph-high (CSbbph 4); 10y-RFS, RFS rate at 10years.

Mentions: Furthermore, we evaluated the prognostic effect of the combined expression of PARP1, γH2AX, BRCA1, and BRCA2. When we focused our analysis on the expressional status of BRCA1 and BRCA2, PARP1 expression predicted shorter OS and RFS in the BRCA1−, BRCA1+, BRCA2−, and BRCA2+ subgroups (Table 3). PARP1 expression also predicted shorter OS in the both γH2AX- and γH2AX+ subgroups (Table 3). γH2AX positivity was associated with shorter OS and RFS in the BRCA1+, BRCA2+, and PARP1+ subgroups (Table 3). Because the expressions of PARP1, γH2AX, BRCA1, and BRCA2 were closely related (Table 1), the combined score for the immunohistochemical expression of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph) was established with the sum of positivity of BRCA1, BRCA2, PARP1, and γH2AX (negative, 0; positive, 1; i.e., BRCA1+/BRCA2+/PARP1+/γH2AX+ = 1 + 1 + 1 + 1 = CSbbph 4). The CSbbph ranged from zero (BRCA1−/BRCA2−/PARP1−/γH2AX-) to four (BRCA1+/BRCA2+/PARP1+/γH2AX+). Thereafter, CSbbph scores were grouped as CSbbph-low (CSbbph 0-1), CSbbph-intermediate (CSbbph 2-3), and CSbbph-high (CSbbph 4). Among the 192 general cases of BCA, CSbbph was significantly associated with OS (P < .001) and RFS (P < .001; Figure 3 and Table 2). The OS rates at 10 years (10y-OS) of the CSbbph-low, the CSbbph-intermediate, and the CSbbph-high subgroups were 95%, 79%, and 35%, respectively (Figure 3).


Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients.

Park SH, Noh SJ, Kim KM, Bae JS, Kwon KS, Jung SH, Kim JR, Lee H, Chung MJ, Moon WS, Kang MJ, Jang KY - Transl Oncol (2015)

Prognostic significance of the combined expression pattern of PARP1, γH2AX, BRCA1, and BRCA2 in 192 BCAs. Kaplan-Meier survival analysis for OS (A) and RFS (B) between the subgroups classified according to CSbbph. CSbbph was established with the sum of positivity of BRCA1, BRCA2, PARP1, and γH2AX (negative, 0; positive, 1). CSbbph scores were grouped as CSbbph-low (CSbbph 0-1), CSbbph-intermediate (CSbbph 2-3), and CSbbph-high (CSbbph 4); 10y-RFS, RFS rate at 10years.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562981&req=5

f0015: Prognostic significance of the combined expression pattern of PARP1, γH2AX, BRCA1, and BRCA2 in 192 BCAs. Kaplan-Meier survival analysis for OS (A) and RFS (B) between the subgroups classified according to CSbbph. CSbbph was established with the sum of positivity of BRCA1, BRCA2, PARP1, and γH2AX (negative, 0; positive, 1). CSbbph scores were grouped as CSbbph-low (CSbbph 0-1), CSbbph-intermediate (CSbbph 2-3), and CSbbph-high (CSbbph 4); 10y-RFS, RFS rate at 10years.
Mentions: Furthermore, we evaluated the prognostic effect of the combined expression of PARP1, γH2AX, BRCA1, and BRCA2. When we focused our analysis on the expressional status of BRCA1 and BRCA2, PARP1 expression predicted shorter OS and RFS in the BRCA1−, BRCA1+, BRCA2−, and BRCA2+ subgroups (Table 3). PARP1 expression also predicted shorter OS in the both γH2AX- and γH2AX+ subgroups (Table 3). γH2AX positivity was associated with shorter OS and RFS in the BRCA1+, BRCA2+, and PARP1+ subgroups (Table 3). Because the expressions of PARP1, γH2AX, BRCA1, and BRCA2 were closely related (Table 1), the combined score for the immunohistochemical expression of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph) was established with the sum of positivity of BRCA1, BRCA2, PARP1, and γH2AX (negative, 0; positive, 1; i.e., BRCA1+/BRCA2+/PARP1+/γH2AX+ = 1 + 1 + 1 + 1 = CSbbph 4). The CSbbph ranged from zero (BRCA1−/BRCA2−/PARP1−/γH2AX-) to four (BRCA1+/BRCA2+/PARP1+/γH2AX+). Thereafter, CSbbph scores were grouped as CSbbph-low (CSbbph 0-1), CSbbph-intermediate (CSbbph 2-3), and CSbbph-high (CSbbph 4). Among the 192 general cases of BCA, CSbbph was significantly associated with OS (P < .001) and RFS (P < .001; Figure 3 and Table 2). The OS rates at 10 years (10y-OS) of the CSbbph-low, the CSbbph-intermediate, and the CSbbph-high subgroups were 95%, 79%, and 35%, respectively (Figure 3).

Bottom Line: In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph) was an additional independent prognostic predictor for OS (P < .001) and RFS (P < .001).The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1) subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4) subgroup.This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents.

View Article: PubMed Central - PubMed

Affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA, USA.

No MeSH data available.


Related in: MedlinePlus