PTEN protein expression in malignant pleural mesothelioma

被引:23
作者
Agarwal, Vijay [1 ,2 ,3 ]
Campbell, Anne [1 ,4 ]
Beaumont, Kate L. [1 ]
Cawkwell, Lynn [1 ,2 ,5 ]
Lind, Michael J. [1 ,2 ,3 ]
机构
[1] Univ Hull, Canc Biol Prote Grp, Postgrad Med Inst, Kingston Upon Hull HU6 7RX, N Humberside, England
[2] Hull York Med Sch, Kingston Upon Hull, N Humberside, England
[3] Hull & East Yorkshire NHS Trust, Queens Ctr Oncol & Haematol, Kingston Upon Hull, N Humberside, England
[4] Hull & East Yorkshire NHS Trust, Dept Histopathol, Kingston Upon Hull, N Humberside, England
[5] Castle Hill Hosp, Res Labs, Kingston Upon Hull HU16 5JQ, N Humberside, England
关键词
AKT; Immunohistochemistry; Mesothelioma; MTOR pathway; PTEN; TUMOR-SUPPRESSOR GENE; PTEN/MMAC1; GENE; PROSTATE-CANCER; GERMLINE MUTATIONS; PHASE-III; PHOSPHATASE; BREAST; INACTIVATION; CISPLATIN; SUBSET;
D O I
10.1007/s13277-012-0615-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Malignant pleural mesothelioma is associated with poor prognosis and despite recent advances in chemotherapy, the median survival is still approximately 12 months. Loss of phosphatase and tensin homolog (PTEN) protein expression may lead to constitutive activation of AKT resulting in cell survival and proliferation. Small studies reported that PTEN protein expression is rarely lost in mesothelioma whilst a larger study demonstrated prognostic significance of PTEN protein expression status with absence in 62 % of cases. We aimed to analyse PTEN protein expression in mesothelioma. Immunohistochemical analysis was performed in 86 archival mesothelioma samples to determine the PTEN protein expression status and statistical analysis was performed to identify any prognostic significance. Mesothelial cells in normal pleura demonstrated positive staining for PTEN protein and served as a positive reference. For mesothelioma samples, the expression of PTEN protein was scored as 0 (negative), 1 (intensity less than that of positive normal pleura reference slide) and 2 (intensity equal to or greater than positive normal pleura reference slide). A total of 23/86 (26.7 %) scored 0, 23/86 (26.7 %) scored 1 and 40/86 (46.5 %) scored 2 for PTEN expression. Univariate analysis demonstrated that lack of PTEN expression was not associated with survival. PTEN protein expression was undetectable in 26.7 % of mesothelioma samples; however, no prognostic significance was identified. Absence of PTEN protein may result in activation of the PI3K/AKT/MTOR pathway. Targeting this pathway with inhibitors further downstream of PTEN may provide a potential therapeutic target in selected patients.
引用
收藏
页码:847 / 851
页数:5
相关论文
共 39 条
[1]   Mutational spectra of PTEN/MMAC1 gene: a tumor suppressor with lipid phosphatase activity [J].
Ali, IU ;
Schriml, LM ;
Dean, M .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1999, 91 (22) :1922-1932
[2]   Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth [J].
Altomare, DA ;
You, HH ;
Xiao, GH ;
Ramos-Nino, ME ;
Skele, KL ;
De Rienzo, A ;
Jhanwar, SC ;
Mossman, BT ;
Kane, AB ;
Testa, JR .
ONCOGENE, 2005, 24 (40) :6080-6089
[3]  
Boström J, 1998, CANCER RES, V58, P29
[4]   The pathogenesis of mesothelioma [J].
Carbone, M ;
Kratzke, RA ;
Testa, JR .
SEMINARS IN ONCOLOGY, 2002, 29 (01) :2-17
[5]   Therapeutic outcome according to histologic subtype in 121 patients with malignant pleural mesothelioma [J].
Ceresoli, GL ;
Locati, LD ;
Ferreri, AJM ;
Cozzarini, C ;
Passoni, P ;
Melloni, G ;
Zannini, P ;
Bolognesi, A ;
Villa, E .
LUNG CANCER, 2001, 34 (02) :279-287
[6]   Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse [J].
Di Cristofano, A ;
De Acetis, M ;
Koff, A ;
Cordon-Cardo, C ;
Pandolfi, PP .
NATURE GENETICS, 2001, 27 (02) :222-224
[7]   Analysis of PTEN and the 10q23 region in primary prostate carcinomas [J].
Feilotter, HE ;
Nagai, MA ;
Boag, AH ;
Eng, C ;
Mulligan, LM .
ONCOGENE, 1998, 16 (13) :1743-1748
[8]   Phase II study of erlotinib in patients with malignant pleural mesothelioma: A Southwest Oncology Group study [J].
Garland, Linda L. ;
Rankin, Cathryn ;
Gandara, David R. ;
Rivkin, Saul E. ;
Scott, Katherine M. ;
Nagle, Raymond B. ;
Klein-Szanto, Andres J. P. ;
Testa, Joseph R. ;
Altomare, Deborah A. ;
Borden, Ernest C. .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (17) :2406-2413
[9]   Mutation and expression analysis of the putative prostate tumour-suppressor gene PTEN [J].
Gray, IC ;
Stewart, LMD ;
Phillips, SMA ;
Hamilton, JA ;
Gray, NE ;
Watson, GJ ;
Spurr, NK ;
Snary, D .
BRITISH JOURNAL OF CANCER, 1998, 78 (10) :1296-1300
[10]  
Grosso F, 2012, FUTURE ONCOL, V8, P293, DOI [10.2217/FON.12.14, 10.2217/fon.12.14]