Correlation of protein expression, Gleason score and DNA ploidy in prostate cancer

Abstract Background The prevalence and molecular characteristics of deficient mismatch repair prostate cancer in the Japanese population have scarcely been investigated. Methods Immunohistochemistry for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed in formalin-fixed paraffin-embedded sections prepared from resected primary prostate cancers in patients who underwent prostatectomy at our institution between January 2001 and May 2016. Genetic and/or epigenetic alterations of mismatch repair genes were investigated in patients with any loss of mismatch repair protein expression in the tumour. Results Of the 337 patients, four (1.2%) showed loss of mismatch repair protein expression on immunohistochemistry. All four patients showed loss of both MSH2 and MSH6 protein expression. Genetic testing was performed in two of the four patients, demonstrating no pathogenic germline alterations were present. In each of these two patients, at least one somatic alteration inactivating MSH2 without MSH2 hypermethylation was identified, leading to the diagnosis of supposed ‘Lynch-like syndrome’. Patients with deficient mismatch repair prostate cancer were at a significantly higher stage (pT2pN0 vs. pT3-4pN0/pTanypN1, P = 0.02) and had a greater Gleason score (<8 vs. ≥8, P < 0.01) than those with proficient mismatch repair prostate cancer. Conclusions The prevalence of deficient mismatch repair prostate cancer in the Japanese hospital-based prostatectomized population was extremely low. To improve screening efficacy for deficient mismatch repair prostate cancer, screening candidates can be limited to patients with locally advanced, node-positive and/or Gleason score of 8 or greater prostate cancer. Universal tumour screening for Lynch syndrome seems ineffective in patients with prostate cancer.

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DNA Ploidy as Surrogate for Biopsy Gleason Score for Preoperative Organ Versus Nonorgan-confined Prostate Cancer Prediction

Urology ◽

10.1016/j.urology.2008.09.060 ◽

2009 ◽

Vol 73 (5) ◽

pp. 1092-1097 ◽

Cited By ~ 12

Author(s):

Sumit Isharwal ◽

M. Craig Miller ◽

Jonathan I. Epstein ◽

Leslie A. Mangold ◽

Elizabeth Humphreys ◽

...

Keyword(s):

Prostate Cancer ◽

Gleason Score ◽

Dna Ploidy ◽

Cancer Prediction ◽

Biopsy Gleason Score

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Large Scale Genomic Instability as an Additive Prognostic Marker in Early Prostate Cancer

Analytical Cellular Pathology ◽

10.1155/2009/384362 ◽

2009 ◽

Vol 31 (4) ◽

pp. 251-259

Author(s):

Maria E. Pretorius ◽

Håkon Wæhre ◽

Vera M. Abeler ◽

Ben Davidson ◽

Ljiljana Vlatkovic ◽

...

Keyword(s):

Prostate Cancer ◽

Prognostic Factor ◽

Clinical Outcome ◽

Gleason Score ◽

Large Scale ◽

Dna Ploidy ◽

Univariate Analysis ◽

Disease Recurrence ◽

Observation Time ◽

Surgical Margins

Background: The clinical outcome for the individual prostate cancer patient is often difficult to predict, due to lack of reliable independent prognostic biomarkers. We tested DNA ploidy as a prognostic factor for clinical outcome in 186 patients treated with radical prostatectomy.Methods: DNA ploidy was measured using an automatic image cytometry system and correlated with preoperative PSA, age at surgery, Mostofi grade, surgical margins and Gleason score.Results: The mean follow up time after operation was 73.3 months (range 2–176 months). Of the 186 prostatectomies, 96 were identified as diploid, 61 as tetraploid and 29 as aneuploid. Twenty-three per cent, 36% and 62% of the diploid, tetraploid and aneuploid cases respectively, suffered from relapse during the observation time. DNA ploidy, Gleason score, Mostofi grading, surgical margins and preoperative PSA were all significant predictors of relapse in a univariate analysis. On multivariate analysis, only Gleason score and DNA ploidy proved to be independently predictors of disease recurrence. Furthermore, among the 68 cases identified with Gleason score 7, DNA ploidy was the only significant predictor of disease recurrence.Conclusion: Our data suggest that DNA ploidy should be included as an important additive prognostic factor for prostate cancer, especially for patients identified with Gleason score 7 tumours.

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Phospholipase D2 in prostate cancer: protein expression changes with Gleason score

British Journal of Cancer ◽

10.1038/s41416-019-0610-7 ◽

2019 ◽

Vol 121 (12) ◽

pp. 1016-1026 ◽

Cited By ~ 1

Author(s):

Amanda R. Noble ◽

Karen Hogg ◽

Rakesh Suman ◽

Daniel M. Berney ◽

Sylvain Bourgoin ◽

...

Keyword(s):

Prostate Cancer ◽

Protein Expression ◽

Cell Viability ◽

Gleason Score ◽

Cell Movement ◽

Western World ◽

Prostate Cell ◽

Prostate Epithelial Cells ◽

Downstream Effects ◽

Castrate Resistant

Abstract Background Phospholipases D1 and D2 (PLD1/2) are implicated in tumorigenesis through their generation of the signalling lipid phosphatidic acid and its downstream effects. Inhibition of PLD1 blocks prostate cell growth and colony formation. Here a role for PLD2 in prostate cancer (PCa), the major cancer of men in the western world, is examined. Methods PLD2 expression was analysed by immunohistochemistry and western blotting. The effects of PLD2 inhibition on PCa cell viability and cell motility were measured using MTS, colony forming and wound-healing assays. Results PLD2 protein is expressed about equally in luminal and basal prostate epithelial cells. In cells from different Gleason-scored PCa tissue PLD2 protein expression is generally higher than in non-tumorigenic cells and increases in PCa tissue scored Gleason 6–8. PLD2 protein is detected in the cytosol and nucleus and had a punctate appearance. In BPH tissue stromal cells as well as basal and luminal cells express PLD2. PLD2 protein co-expresses with chromogranin A in castrate-resistant PCa tissue. PLD2 inhibition reduces PCa cell viability, colony forming ability and directional cell movement. Conclusions PLD2 expression correlates with increasing Gleason score to GS8. PLD2 inhibition has the potential to reduce PCa progression.

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