Prognostic significance of CD117 expression and TP53 missense mutations in triple-negative breast cancer

被引:14
作者
Luo, Yanli [1 ]
Huang, Wentao [1 ]
Zhang, Huizhen [1 ]
Liu, Guang [2 ]
机构
[1] Shanghai Jiao Tong Univ, Dept Pathol, Affiliated Peoples Hosp 6, 600 Yishan Rd, Shanghai 200233, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Vasc Surg, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China
关键词
triple-negative breast cancer; cluster of differentiation 117; tumor protein P53 missense mutations; vascular invasion; prognosis; IMMUNOHISTOCHEMICAL DETECTION; GENE-MUTATIONS; P53; KIT; CARCINOMAS; PATTERNS; INVASION; SUBTYPE; MARKER; CELLS;
D O I
10.3892/ol.2018.8104
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Triple-negative breast cancer (TNBC) is extremely aggressive and associated with poor prognosis. There are no known predictive or prognostic markers for TNBC. Inhibition of tumor protein P53 (TP53) has been demonstrated to increase the levels of cluster of differentiation 117 (CD117) in human colorectal cancer cells. However, the function of TP53 in the regulation of CD117 in TNBC has, to the best of our knowledge, not been reported. In the present study, the association between the expression of CD117 protein and TP53 mutations was investigated, and their prognostic value in patients with TNBC was assessed. A total of 58 TNBC and 48 non-TNBC breast cancer tissue samples were assessed for the expression of CD117, p53 and TP53 mutations. The marker of proliferation Ki-67 (MKI67) proliferation index and vascular invasion index (obtained by measuring D2-40 and CD34) was investigated via immunohistochemistry, and mutations in exons 4-8 of TP53 were measured using direct sequencing. Associations between CD117 and p53 levels or TP53 mutations and clinical parameters were statistically evaluated. The rates of CD117 or MKI67 positivity, CD117(+)/TP53 missense mutation(+), TP53 missense mutations or recurrence were significantly higher in patients with TNBC than in patients with non-TNBC. In TNBC tissues, the presence of CD117 was associated with TP53 missense mutations (P=0.031), vascular invasion, recurrence and MKI67. CD117(+)/TP53 missense mutation+ also associated with vascular invasion, recurrence and MKI67. Under univariate analysis, MKI67, vascular invasion, CD117, CD117(+)/TP53 missense mutation(+) and TP53 missense mutations were associated with the overall survival of patients with TNBC. Multivariate analysis revealed that vascular invasion and CD117(+)/TP53 missense mutation(+) in primary tumors were independent prognostic factors in patients with TNBC. In conclusion, CD117+/TP53 missense mutation+ was associated with MKI67, vascular invasion and tumor recurrence in TNBC. The presence of CD117 and TP53 missense mutations together in the primary tumors was an independent prognostic factor for survival of patients with TNBC.
引用
收藏
页码:6161 / 6170
页数:10
相关论文
共 41 条
[1]   Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells [J].
Abraham, Sheela A. ;
Hopcroft, Lisa E. M. ;
Carrick, Emma ;
Drotar, Mark E. ;
Dunn, Karen ;
Williamson, Andrew J. K. ;
Korfi, Koorosh ;
Baquero, Pablo ;
Park, Laura E. ;
Scott, Mary T. ;
Pellicano, Francesca ;
Pierce, Andrew ;
Copland, Mhairi ;
Nourse, Craig ;
Grimmond, Sean M. ;
Vetrie, David ;
Whetton, Anthony D. ;
Holyoake, Tessa L. .
NATURE, 2016, 534 (7607) :341-+
[2]   Gene expression profiling of single circulating tumor cells in ovarian cancer - Establishment of a multi-marker gene panel [J].
Blassl, Christina ;
Kuhlmann, Jan Dominik ;
Webers, Alessandra ;
Wimberger, Pauline ;
Fehm, Tanja ;
Neubauer, Hans .
MOLECULAR ONCOLOGY, 2016, 10 (07) :1030-1042
[3]   p53 as a Specific Prognostic Factor in Triple-negative Breast Cancer [J].
Chae, Byung Joo ;
Bae, Ja Seong ;
Lee, Ahwon ;
Park, Woo Chan ;
Seo, Young Jin ;
Song, Byung Joo ;
Kim, Jung Soo ;
Jung, Sang Seol .
JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 2009, 39 (04) :217-224
[4]  
Changavi Arathi A, 2015, J Lab Physicians, V7, P79, DOI 10.4103/0974-2727.163129
[5]   Influence of mutation type on prognostic and predictive values of TP53 status in primary breast cancer patients [J].
Dobes, Petr ;
Podhorec, Jan ;
Coufal, Oldrich ;
Jureckova, Andrea ;
Petrakova, Katarina ;
Vojtesek, Borivoj ;
Hrstka, Roman .
ONCOLOGY REPORTS, 2014, 32 (04) :1695-1702
[6]   CD117 expression in operable oesophageal squamous cell carcinomas predicts worse clinical outcome [J].
Fan, Huijie ;
Yuan, Yuan ;
Wang, Junsheng ;
Zhou, Fuyou ;
Zhang, Mingzhi ;
Giercksky, Karl-Erik ;
Nesland, Jahn M. ;
Suo, Zhenhe .
HISTOPATHOLOGY, 2013, 62 (07) :1028-1037
[7]   Prognostic and predictive value of TP53 mutations in node-positive breast cancer patients treated with anthracycline- or anthracycline/taxane-based adjuvant therapy: results from the BIG 02-98 phase III trial [J].
Fernandez-Cuesta, Lynnette ;
Oakman, Catherine ;
Falagan-Lotsch, Priscila ;
Smoth, Ke-seay ;
Quinaux, Emmanuel ;
Buyse, Marc ;
Dolci, M. Stella ;
De Azambuja, Evandro ;
Hainaut, Pierre ;
Dell'Orto, Patrizia ;
Larsimont, Denis ;
Francis, Prudence A. ;
Crown, John ;
Piccart-Gebhart, Martine ;
Viale, Giuseppe ;
Di Leo, Angelo ;
Olivier, Magali .
BREAST CANCER RESEARCH, 2012, 14 (03)
[8]   BRCA-1 methylation and TP53 mutation in triple-negative breast cancer patients without pathological complete response to taxane-based neoadjuvant chemotherapy [J].
Foedermayr, Mathilde ;
Sebesta, Miriam ;
Rudas, Margaretha ;
Berghoff, Anna S. ;
Promberger, Regina ;
Preusser, Matthias ;
Dubsky, Peter ;
Fitzal, Florian ;
Gnant, Michael ;
Steger, Guenther G. ;
Weltermann, Ansgar ;
Zielinski, Christoph C. ;
Zach, Otto ;
Bartsch, Rupert .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2014, 73 (04) :771-778
[9]   Triple-Negative Breast Cancer [J].
Foulkes, William D. ;
Smith, Ian E. ;
Reis-Filho, Jorge S. .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 363 (20) :1938-1948
[10]   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 [J].
Fountzilas, George ;
Giannoulatou, Eleni ;
Alexopoulou, Zoi ;
Zagouri, Flora ;
Timotheadou, Eleni ;
Papadopoulou, Kyriaki ;
Lakis, Sotiris ;
Bobos, Mattheos ;
Poulios, Christos ;
Sotiropoulou, Maria ;
Lyberopoulou, Aggeliki ;
Gogas, Helen ;
Pentheroudakis, George ;
Pectasides, Dimitrios ;
Koutras, Angelos ;
Christodoulou, Christos ;
Papandreou, Christos ;
Samantas, Epaminontas ;
Papakostas, Pavlos ;
Kosmidis, Paris ;
Bafaloukos, Dimitrios ;
Karanikiotis, Charisios ;
Dimopoulos, Meletios-Athanassios ;
Kotoula, Vassiliki .
ONCOTARGET, 2016, 7 (22) :32731-32753