TMPRSS2-ERG gene fusion is associated with low Gleason scores and not with high-grade morphological features

Abstract

TMPRSS2-ERG gene rearrangement is seen in about half of clinically localized prostate cancers, yet controversy exists with regard to its prognostic implications. Similarly, the relationship of TMPRSS2-ERG fusion to Gleason score and morphology remains uncertain. We assigned Gleason scores and recorded morphological features for 521 clinically localized prostate cancers sampled in triplicate and arrayed in eight tissue microarray blocks. Fluorescence in situ hybridization was performed to delineate TMPRSS2-ERG aberrations. Using maximum Gleason score, based on three core evaluation, and overall Gleason score, based on prostatectomy sections, Fisher's exact test was performed for tumors with TMPRSS2-ERG translocation/deletion, copy number increase (≥ 3) of the TMPRSS2-ERG region without translocation/deletion, and copy number increase and concomitant translocation/deletion. In all, 217 (42%) translocation/deletion and 30 (5.9%) copy number increase-alone cases were detected. Among 217 translocation/deletion cases, 32 had translocation/deletion with copy number increase. In all, 237, 200, and 75 cancers had maximum core-specific Gleason score of 6, 7, and 8-10, respectively. Tumors with translocation/deletion tended toward lower Gleason scores than those without (P=0.002) with similar results for overall Gleason score (P=0.02); copy number increase cases tended toward higher Gleason scores than those without (P<0.001). Gleason score of 8-10 tumors demonstrated lower odds of translocation/deletion (odds ratio (OR) 0.38; 95% CI 0.21-0.68) and higher odds of copy number increase alone (OR 7.33; 95% CI 2.65-20.31) or copy number increase+translocation/deletion (OR 3.03; 95% CI 1.12-8.15) relative to Gleason score of <7 tumors. No significant difference in TMPRSS2-ERG incidence was observed between patients with and without cribriform glands, glomerulations, signet-ring cells, or intraductal cancer (P=0.821, 0.095, 0.132, 0.375). TMPRSS2-ERG gene fusion is associated with lower core-specific and overall Gleason scores and not with high-grade morphologies. Conversely, TMPRSS2-ERG copy number increase, with or without rearrangement, is associated with higher Gleason score. These findings indicate that translocation/deletion of TMPRSS2-ERG is not associated with histological features of aggressive prostate cancer.

Figure 1

Four major FISH patterns: (a) Wildtype: two sets of triplet orange (3’ERG), red (3’TMPRSS2) and green (5’TMPRSS2) signals in each cell; (b) Deletion: one orange-green doublet and loss of corresponding red signal in one allele and a wildtype second allele; (c) Translocation: an orange-green doublet in one allele and retention, yet separation of one red (3’TMPRSS2) signal; the other allele is wildtype; (d) Copy number increase: greater than two wildtype signals in each cell.

Figure 2

Specific morphologic features evaluated: (a) cribriform glands; (b) glomerulations; (c) signet ring cells; (d) intraductal carcinoma; (e) mucinous fibroplasia; (f) mucinous features.

Figure 2

Specific morphologic features evaluated: (a) cribriform glands; (b) glomerulations; (c) signet ring cells; (d) intraductal carcinoma; (e) mucinous fibroplasia; (f) mucinous features.

Figure 2

Specific morphologic features evaluated: (a) cribriform glands; (b) glomerulations; (c) signet ring cells; (d) intraductal carcinoma; (e) mucinous fibroplasia; (f) mucinous features.

Figure 2

Specific morphologic features evaluated: (a) cribriform glands; (b) glomerulations; (c) signet ring cells; (d) intraductal carcinoma; (e) mucinous fibroplasia; (f) mucinous features.

Figure 2

Specific morphologic features evaluated: (a) cribriform glands; (b) glomerulations; (c) signet ring cells; (d) intraductal carcinoma; (e) mucinous fibroplasia; (f) mucinous features.

Figure 2

Specific morphologic features evaluated: (a) cribriform glands; (b) glomerulations; (c) signet ring cells; (d) intraductal carcinoma; (e) mucinous fibroplasia; (f) mucinous features.