TP53 mutations and protein immunopositivity may predict for poor outcome but also for trastuzumab benefit in patients with early breast cancer treated in the adjuvant setting.
TP53 mutations and protein immunopositivity may predict for poor outcome but also for trastuzumab benefit in patients with early breast cancer treated in the adjuvant setting.
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DOI：
10.18632/oncotarget.9022
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发表时间：
2016-05-31
期刊：
影响因子：
--
通讯作者：
Kotoula V
中科院分区：
文献类型：
--
作者：
Fountzilas G;Giannoulatou E;Alexopoulou Z;Zagouri F;Timotheadou E;Papadopoulou K;Lakis S;Bobos M;Poulios C;Sotiropoulou M;Lyberopoulou A;Gogas H;Pentheroudakis G;Pectasides D;Koutras A;Christodoulou C;Papandreou C;Samantas E;Papakostas P;Kosmidis P;Bafaloukos D;Karanikiotis C;Dimopoulos MA;Kotoula V
我们研究了PIK 3CA和TP 53突变以及p53蛋白状态对在曲妥珠单抗治疗前后的临床试验中接受蒽环类-紫杉烷类辅助化疗的患者结局的影响。在380例（21.5%）和458例（25.9%）病例中分别发现TP 53和PIK 3CA突变，包括104例（5.9%）共突变肿瘤;在848例（53.5%）肿瘤中观察到p53免疫阳性。TP 53突变（p < 0.001）和p53蛋白阳性（p = 0.001）在HER 2阳性和三阴性（TNBC）肿瘤中更常见，而PIK 3CA突变在管腔A/B肿瘤中更常见（p < 0.001）。TP 53突变状态和p53蛋白表达（而非PIK 3CA突变状态）与曲妥珠单抗治疗的无病生存期相互作用;携带TP 53突变或p53蛋白免疫阳性的肿瘤患者在接受曲妥珠单抗治疗时表现更好，而在接受曲妥珠单抗治疗的患者中，具有上述特征的患者表现最好（突变的相互作用p = 0.017; IHC的p = 0.015）。多变量分析后，上述相互作用在HER 2阳性患者中仍然显著;在整个队列中，TP 53突变在Luminal A/B（p = 0.003）和TNBC（p = 0.025）患者中不利; p53免疫阳性在曲妥珠单抗治疗患者中非常有利（p = 0.009）。对1766例石蜡标本进行TP 53和PIK 3CA基因突变检测，并对检测结果进行半导体测序。其中，1585例也提供了免疫组化（IHC; 10%阳性截止值）评估的p53蛋白状态信息。TP 53突变导致Luminal A/B和TNBC肿瘤患者预后不良，而p53免疫阳性可能预示曲妥珠单抗在辅助治疗中的获益。
We investigated the impact of PIK3CA and TP53 mutations and p53 protein status on the outcome of patients who had been treated with adjuvant anthracycline-taxane chemotherapy within clinical trials in the pre- and post-trastuzumab era. TP53 and PIK3CA mutations were found in 380 (21.5%) and 458 (25.9%) cases, respectively, including 104 (5.9%) co-mutated tumors; p53 immunopositivity was observed in 848 tumors (53.5%). TP53 mutations (p < 0.001) and p53 protein positivity (p = 0.001) were more frequent in HER2-positive and triple negative (TNBC) tumors, while PIK3CA mutations were more frequent in Luminal A/B tumors (p < 0.001). TP53 mutation status and p53 protein expression but not PIK3CA mutation status interacted with trastuzumab treatment for disease-free survival; patients with tumors bearing TP53 mutations or immunopositive for p53 protein fared better when treated with trastuzumab, while among patients treated with trastuzumab those with the above characteristics fared best (interaction p = 0.017 for mutations; p = 0.015 for IHC). Upon multivariate analysis the above interactions remained significant in HER2-positive patients; in the entire cohort, TP53 mutations were unfavorable in patients with Luminal A/B (p = 0.003) and TNBC (p = 0.025); p53 immunopositivity was strongly favorable in patients treated with trastuzumab (p = 0.009). TP53 and PIK3CA mutation status was examined in 1766 paraffin tumor DNA samples with informative semiconductor sequencing results. Among these, 1585 cases were also informative for p53 protein status assessed by immunohistochemistry (IHC; 10% positivity cut-off). TP53 mutations confer unfavorable prognosis in patients with Luminal A/B and TNBC tumors, while p53 immunopositivity may predict for trastuzumab benefit in the adjuvant setting.
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影响因子：
8.8
作者：
Cizkova M;Dujaric ME;Lehmann-Che J;Scott V;Tembo O;Asselain B;Pierga JY;Marty M;de Cremoux P;Spyratos F;Bieche I
通讯作者：
Bieche I
影响因子：
2.8
作者：
Hill, KA;Sommer, SS
通讯作者：
Sommer, SS
影响因子：
2.7
作者：
Bastien RR;Rodríguez-Lescure Á;Ebbert MT;Prat A;Munárriz B;Rowe L;Miller P;Ruiz-Borrego M;Anderson D;Lyons B;Álvarez I;Dowell T;Wall D;Seguí MÁ;Barley L;Boucher KM;Alba E;Pappas L;Davis CA;Aranda I;Fauron C;Stijleman IJ;Palacios J;Antón A;Carrasco E;Caballero R;Ellis MJ;Nielsen TO;Perou CM;Astill M;Bernard PS;Martín M
通讯作者：
Martín M
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
DOI：
10.1093/jnci/85.3.200
发表时间：
1993-02-03
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
ALLRED, DC;CLARK, GM;MCGUIRE, WL
通讯作者：
MCGUIRE, WL