UNASSIGNED: @entity263 often manifests as morphologically distinct @entity5 foci and is frequently found adjacent to presumed precursor lesions such as @entity5436 ( @entity5436 ). While there is some evidence to suggest that these lesions can be related and exist on a pathological and morphological continuum, the precise clonal and temporal relationships between precursor lesions and invasive @entity5 within @entity5 remain undefined. Here, we used molecular genetic, cytogenetic, and histological analyses to delineate clonal, temporal, and spatial relationships between @entity5436 and @entity5 with distinct morphological and molecular features. First, while confirming the previous finding that a substantial fraction of @entity4623 associated with ERG-positive @entity5 share rearrangements and overexpression of ERG, we found that a significant subset of such @entity5436 glands exhibit only partial positivity for ERG. This suggests that such ERG-positive @entity5436 cells either rapidly invade to form @entity420 or represent @entity5 cells that have partially invaded the ductal and acinar space in a retrograde manner. To clarify these possibilities, we used ERG expression status and @entity5435 -ERG genomic breakpoints as markers of clonality, and @entity983 deletion status to track temporal evolution of clonally related lesions. We confirmed that morphologically distinct @entity5436 and nearby invasive @entity5 are clonally related. Further, we found that a significant fraction of ERG-positive, @entity983 -negative @entity263 (IDC-P) lesions are most likely clonally derived from adjacent @entity983 -negative @entity420 , indicating that such @entity983 -negative @entity5436 and @entity75 arise from, rather than give rise to, the nearby invasive @entity420 . These data suggest that invasive @entity420 can morphologically mimic @entity5436 through retrograde colonization of benign glands with @entity5 cells. Similar clonal relationships were also seen for @entity3821 adjacent to invasive @entity420 . These findings represent a potentially undervalued indicator of pre-existing @entity263 and have significant implications for @entity263 diagnosis and risk stratification. Copyright    2015 Pathological Society of Great Britain and Ireland. Published by John Wiley _ Sons, Ltd.

Molecular evidence that invasive @entity420 can mimic @entity5436 ( XXXX ) and @entity3821 through retrograde glandular colonization.

@entity5435 :: ('7113', 'Gene') :: ['TMPRSS2'] @entity3821 :: ('MESH:D002285', 'Disease') :: ['intraductal carcinoma'] @entity263 :: ('MESH:D011471', 'Disease') :: ['invasive prostate cancer', 'prostate cancer', 'Prostate cancer', 'HGPIN and intraductal carcinoma'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers', 'cancer', 'individual tumours', 'cancer lesions', 'tumour'] @entity75 :: ('MESH:D001927', 'Disease') :: ['IDC-P lesions'] @entity983 :: ('5728', 'Gene') :: ['PTEN'] @entity4623 :: ('MESH:D011469', 'Disease') :: ['HGPIN lesions'] @entity420 :: ('MESH:D000230', 'Disease') :: ['adenocarcinomas', 'adenocarcinoma'] @entity5436 :: ('MESH:D019048', 'Disease') :: ['high-grade prostatic intraepithelial neoplasia', 'HGPIN']
@entity5436 :: (MESH:D019048,Disease) :: ['PIN']
