부산대학교 도서관

Recent studies suggest that expansile cribriform morphology contributes to adverse oncologic outcomes. Among specific tumor suppressor gene alterations associated with cribriform morphology, PTEN and CHD1 are known to confer an aggressive behavior. However, alteration of both genes among patients with expansile cribriform Gleason pattern 4 prostate cancer (PCa) and their correlation with oncologic outcomes have not been extensively studied. Herein, we sought to determine the impact of expansile cribriform morphology and somatic PTEN and CHD1 gene loss on oncologic outcomes for patients undergoing radical;prostatectomy (RP) for grade groups 2-5 PCa. We reviewed the medical records from patients who underwent RP for Gleason score 7 or higher PCa from 2000 to 2002 at our institution. Experienced GU pathologists re reviewed all pathology specimens to verify Gleason scores and percentages of each Gleason pattern. Disagreements were solved by consensus. Gleason pattern 4 was characterized as poorly formed/fused glands, small uniform cribriform glands, expansile cribriform glands, mucinous glands, or glands with glomerulations. Tissue microarrays (TMAs) were constructed with quadruplicate 0.6 mm cores containing the Gleason pattern 4 from each case. Fluorescence in situ hybridization (FISH) using probes detecting PTEN and CHD1 was performed on TMAs (Figure). The association of expansile cribriform glands with each gene loss was assessed by Cox regression analyses. The association of Gleason 4 histological patterns and gene loss with biochemical recurrence (BCR), systemic progression (SP), and death from prostate cancer was assessed using Cox proportional hazard regression models. A total of 409 and 262 patients were included in the FISH and survival;analyses, respectively. Median follow-up from RP to death or last follow up for the entire cohort was 15.1 years (IQR: 11.5 – 16.3). Expansile cribriform morphology was significantly associated with worse BCR (p<0.0001), SP (p<0.0001), and death from PCa (p<0.001) compared to other Gleason pattern 4 morphologies (Table). Only PTEN gene loss (as opposed to CHD1) was associated with worse oncologic outcomes compared to patients without any gene loss (Table). Overall, CHD1 and PTEN gene loss were identified in 18.3% and 24.7% of patients with any Gleason pattern 4. Expansile cribriform Gleason pattern 4 was more commonly associated with CHD1 gene loss compared to other Gleason pattern 4 morphologies (p=0.004). On the other hand, PTEN gene loss was not preferentially found among expansile cribriform morphology compared to other Gleason 4 patterns (p=0.08). Expansile cribriform Gleason 4 differs from other Gleason 4 patterns. Morphologically, these glands are large with less open/ill formed lumens and irregular sprawling edges. Genetically, CHD1 loss is commonly identified within these glands. More importantly, patients with expansile cribriform glands and PTEN gene loss seem to have worse oncologic outcomes. Pending external validation, these data suggest that an expansile cribriform architecture could be more appropriately classified as Gleason pattern 5. [ABSTRACT FROM AUTHOR]