Peripheral zone prostate cancers: Location and intraprostatic patterns of spread at histopathology

Haffner, Jérémie; Potiron, E.; Bouyé, S.; Puech, Philippe; Leroy, Xavier; Lemaître, L.; Villers, Arnauld

doi:10.1002/pros.20881

Cited by 73 publications

(53 citation statements)

References 17 publications

(34 reference statements)

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“…2 K-L). DLP was chosen because it is histologically and functionally the most closely related to the peripheral zone of the human prostate (21), which is the region where most prostate cancers occur in men (22,23). There was a significant decrease (P = 0.013) in the number of Ki67-positive nuclei between WT/cPten F/F (24.5 ± 6.6%) and KI/cPten F/F (9.5 ± 1.1%) mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression

Furic

Liang

Larsson

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

450

566

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Translational regulation plays a critical role in the control of cell growth and proliferation. A key player in translational control is eIF4E, the mRNA 5′ cap-binding protein. Aberrant expression of eIF4E promotes tumorigenesis and has been implicated in cancer development and progression. The activity of eIF4E is dysregulated in cancer. Regulation of eIF4E is partly achieved through phosphorylation. However, the physiological significance of eIF4E phosphorylation in mammals is not clear. Here, we show that knock-in mice expressing a nonphosphorylatable form of eIF4E are resistant to tumorigenesis in a prostate cancer model. By using a genome-wide analysis of translated mRNAs, we show that the phosphorylation of eIF4E is required for translational up-regulation of several proteins implicated in tumorigenesis. Accordingly, increased phospho-eIF4E levels correlate with disease progression in patients with prostate cancer. Our findings establish eIF4E phosphorylation as a critical event in tumorigenesis. These findings raise the possibility that chemical compounds that prevent the phosphorylation of eIF4E could act as anticancer drugs. PTEN | translational controlA berrations in the control of mRNA translation initiation have been documented in many tumor types (1-4). Translation initiation is controlled in part by eIF4E, the mRNA 5′ cap-binding protein. eIF4E is a proto-oncogene, inasmuch as its overexpression in immortalized rodent fibroblasts or human epithelial cells causes transformation (5, 6), and in mouse models its overexpression engenders tumor formation (7,8). eIF4E is phosphorylated by the MNK1/2 serine/threonine kinases, which are activated in response to mitogenic and stress signaling downstream of ERK1/2 and p38 MAP kinase, respectively (9, 10). eIF4E phosphorylation at serine 209 by MNK1/2 promotes its transformation activity (11,12). To study the role of eIF4E phosphorylation in tumorigenesis in the whole organism, we generated a knock-in (KI) mouse in which eIF4E serine 209 was mutated to alanine. Here, we show that mouse embryonic fibroblasts (MEFs) isolated from eIF4E S209A/S209A embryos display a marked resistance to oncogene-induced transformation. Furthermore, the mutant mice are viable, but are resistant to development of Pten loss-induced prostate cancer, and this resistance is associated with a decrease in MMP3, CCL2, VEGFC, and BIRC2 proteins. Moreover, eIF4E is highly phosphorylated in hormone-refractory prostate cancer, which correlates with poor clinical outcome. These results demonstrate the importance of eIF4E phosphorylation in tumorigenesis and validate the eIF4E phosphorylation pathway as a potential therapeutic target for cancer. ResultsSer209 Is the Only Phosphorylation Site in eIF4E. To address the role of eIF4E phosphorylation in tumorigenesis, a knock-in (KI) mouse in which serine 209 was replaced by an alanine residue was generated. The strategy and targeting vector construction for the generation, selection, and genotyping of the S209A mice is shown in Fig. S1. The eIF4E S...

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Section: Resultsmentioning

confidence: 99%

eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression

Furic

Liang

Larsson

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

450

566

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“…As prostate appearance on the images is impacted by different parameters as the patient age and the final cancer diagnosis, images were selected in a way to be representative of the population. Thus, patients were in the age range 45-68 years with a mean age of 56 , while prostate volumes were in the range 24-82 cm 3 with mean volume of 43 cm 3 . For diagnosis outcome, 14 patients (63.…”

Section: Experiments and Resultsmentioning

confidence: 99%

“…Here, we consider them as the transition zone (TZ). The peripheral zone (PZ) is the area where most prostate cancers grow [3]. Moreover, cancers of these two zones exhibit different behaviors [4].…”

Section: Introductionmentioning

confidence: 99%

Gland and Zonal Segmentation of Prostate on T2W MR Images

et al. 2016

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For many years, prostate segmentation on MR images concerned only the extraction of the entire gland. Currently, in the focal treatment era, there is a continuously increasing need for the separation of the different parts of the organ. In this paper, we propose an automatic segmentation method based on the use of T2W images and atlas images to segment the prostate and to isolate the peripheral and transition zones. The algorithm consists of two stages. First, the target image is registered with each zonal atlas image then the segmentation is obtained by the application of an evidential C-Means clustering. The method was evaluated on a representative and multi-centric image base and yielded mean Dice accuracy values of 0.81, 0.70, and 0.62 for the prostate, the transition zone, and peripheral zone, respectively.

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“…As most cancers have a broad capsule contact and tend to spread along a capsule [16,17], one could have thought that nodular lesions or linear abnormalities parallel to the capsule might have been significant predictors of cancer. However, we did not find the shape of FAs to be a significant predictor of malignancy in PZ.…”

Section: Discussionmentioning

confidence: 99%

Is it possible to model the risk of malignancy of focal abnormalities found at prostate multiparametric MRI?

et al. 2012

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Peripheral zone prostate cancers: Location and intraprostatic patterns of spread at histopathology

Abstract: PZ cancers contours and locations are predictable and conform to histological zone boundaries if <2 cm(3) in volume. Knowledge of PZ cancers origin and pattern of spread in PZ are of importance for imaging diagnosis, guidance for biopsy and focal therapy.

Cited by 73 publications

References 17 publications

eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression

eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression

Gland and Zonal Segmentation of Prostate on T2W MR Images

Is it possible to model the risk of malignancy of focal abnormalities found at prostate multiparametric MRI?

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