Lineage Relationship of Gleason Patterns in Gleason Score 7 Prostate Cancer

Kovtun, Irina V.; Cheville, John C.; Murphy, Stephen J.; Johnson, Sarah H.; Zarei, Shabnam; Kosari, Farhad; Sukov, William R.; Karnes, R. Jeffrey; Vasmatzis, George

doi:10.1158/0008-5472.can-12-2803

Cited by 48 publications

(48 citation statements)

References 33 publications

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“…[8] On the other hand, if Gleason pattern 3 and pattern 4 are distinct entities with rare transitions from pattern 3 to pattern 4, then the TZ might represent a distinct niche in the prostate in which pattern 3 grows preferentially. [17, 18]…”

Section: Discussionmentioning

confidence: 99%

Biologic differences between peripheral and transition zone prostate cancer

et al. 2014

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Background Prostate cancer arises in the transition zone (TZ) in approximately 20-25% of cases. Modern biopsy and surveillance protocols, and advances in prostate cancer imaging, have renewed interest in TZ prostate cancers. We compared TZ and PZ prostate cancer to determine if cancer location is independently associated with better outcomes. Methods We evaluated an expanded cohort of 1534 men who underwent radical prostatectomy between 1983 and 2003 with updated long-term clinical follow-up. Regression models were used to compare the volume of high-grade (Gleason 4 or 5) cancer and total cancer volume by location. Uni- and multi-variable logistic regression models tested the associations between cancer location and adverse pathologic features. Multivariable proportional hazard models were fit to examine cancer recurrence. Results Patients with TZ cancer presented with higher pre-operative serum PSA values (11.07 versus 7.86 ng/mL) and larger total cancer volume (7.1 versus 3.8 cc). Patients with TZ cancer had decreased odds of seminal vesicle invasion (OR 0.08, 95%CI 0.03, 0.21), extra-capsular extension (OR 0.56, 95%CI 0.35,0.92), and lymphovascular invasion (OR 0.48, 95%CI 0.27, 0.87) in multivariable models. TZ cancers were independently associated with decreased hazard of tumor recurrence (HR 0.62, 95%CI 0.43, 0.90). Conclusions TZ cancer prostate is associated with favorable pathologic features and better recurrence-free survival despite being diagnosed with larger cancers and higher PSA values. Tumor location should be taken into account when stratifying patient risk before and after prostatectomy, particularly with the evolving role of imaging in prostate cancer management.

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Section: Discussionmentioning

confidence: 99%

Biologic differences between peripheral and transition zone prostate cancer

et al. 2014

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“…[27][28][29][30] In Gleason score 7, the Gleason pattern 3 and Gleason pattern 4 were collected and analyzed separately. 28 Libraries were prepared using the Illumina Mate Pair (MP) Kit following the manufacturer's instructions and sequenced as two libraries per lane on the Illumina HiSeq platform. [27][28][29][30][31] Data were processed using previously described binary indexing mapping algorithms developed in our group.…”

Section: Isolation Of Dna and Mate Pair Sequencingmentioning

confidence: 99%

“…28 Libraries were prepared using the Illumina Mate Pair (MP) Kit following the manufacturer's instructions and sequenced as two libraries per lane on the Illumina HiSeq platform. [27][28][29][30][31] Data were processed using previously described binary indexing mapping algorithms developed in our group. 32 The read-to-reference-genome-mapping algorithm was modified to map both mate pair sequencing reads across the whole genome.…”

Section: Isolation Of Dna and Mate Pair Sequencingmentioning

confidence: 99%

Integrated analysis of the genomic instability of PTEN in clinically insignificant and significant prostate cancer

et al. 2016

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Patients with clinically insignificant prostate cancer remain a major over-treated population. PTEN loss is one of the most recurrent alterations in prostate cancer associated with an aggressive phenotype, however, the occurrence of PTEN loss in insignificant prostate cancer has not been reported and its role in the separation of insignificant from significant prostate cancer is unclear. An integrated analysis of PTEN loss was, therefore, performed for structural variations, point mutations and protein expression in clinically insignificant (48 cases) and significant (76 cases) prostate cancers treated by radical prostatectomy. Whole-genome mate pair sequencing was performed on tumor cells isolated by laser capture microdissection to characterize PTEN structural alterations. Fluorescence in situ hybridization probes were constructed from the sequencing data to detect the spectrum of these PTEN alterations. PTEN loss by mate pair sequencing and fluorescence in situ hybridization occurred in 2% of insignificant, 13% of large volume Gleason score 6, and 46% of Gleason score 7 and higher cancers. In Gleason score 7 cancers with PTEN loss, PTEN alterations were detected in both Gleason pattern 3 and 4 in 57% of cases by mate pair sequencing, 75% by in situ hybridization and 86% by immunohistochemistry. PTEN loss by sequencing was strongly associated with TMPRSS2-ERG fusion, biochemical recurrence, PTEN loss by in situ hybridization and protein loss by immunohistochemistry. The complex nature of PTEN rearrangements was unveiled by sequencing, detailing the heterogeneous events leading to homozygous loss of PTEN. PTEN point mutation was present in 5% of clinically significant tumors and not in insignificant cancer or high-grade prostatic intraepithelial neoplasia. PTEN loss is infrequent in clinically insignificant prostate cancer, and is associated with higher grade tumors. Detection of PTEN loss in Gleason score 6 cancer in a needle biopsy specimen indicates a higher likelihood of clinically significant prostate cancer. The tumor suppressor gene, PTEN (phosphatase and tensin homolog on chromosome 10), a phosphoinositide 3-phosphatase, negatively regulates the PI3K/ AKT signaling pathway and functions as a tumor suppressor. It is one of the most commonly altered genes in prostate cancer. Mutations in PTEN occur in up to 10% of primary prostate cancers while PTEN deletion occurs in 10-70% of surgically treated cancers and over 50% of metastatic prostate cancers. 1-11 PTEN deletion is associated with poorer cancer specific outcomes, and there is an association of deletion with increasing stage and Gleason score. 7,9,[12][13][14][15][16] Although associated with later stage and higher grade tumors, the frequency of PTEN loss is reported in 3-10% of Gleason score 6 cancers, and 15% of confined pT2 tumors. 12,15 In regards to the proposed precursor lesion, high-grade prostatic intraepithelial neoplasia, the data are inconsistent and limited with five studies to date. In three studies

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“…Определенная внутриопухолевая гетерогенность в отношении степени дифференцировки (наличие оценки 3 и 4 по шкале Глисона в 1 опухолевом очаге) часто отражает клональность опухоли (т. е. часть опухоли с оценкой по шкале Глисона 4 развилась из опухоли с оценкой 3) с общими генетическими перестройками для этих опухолей [49,65]. Это чрезвычайно интерес-ная тема для современных исследований, занимаю-щихся изучением прогрессирования карциномы.…”

Section: обзорunclassified