Premium
Progression of in situ breast cancer directly to lymphovascular invasion by stem cell mediated myoepithelial‐endothelial metaplasia
Author(s) -
Barsky Sanford H,
Mahooti Sepi,
Jones Susie,
Ye Yin
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a385-c
Subject(s) - myoepithelial cell , lymphovascular invasion , stromal cell , pathology , biology , transdifferentiation , cd31 , stem cell , cancer research , angiogenesis , cancer , medicine , microbiology and biotechnology , immunohistochemistry , metastasis , genetics
Progression of in situ breast cancer (DCIS) is thought to involve stromal invasion through a myoepithelial and basement membrane layer followed by lymphovascular invasion (LVI) yet we have observed cases of DCIS with florid LVI without stromal invasion. We conducted observational and experimental studies designed to examine whether DCIS can progress directly to LVI and if so, the proposed mechanism. In the observational studies, the DCIS profiles exhibited the same size distribution as the lymphovascular emboli and both expressed equally strong E‐cadherin and Ki‐67 immunoreactivity, suggesting that the two processes were really the same entity. In addition the DCIS exhibited a progressive loss of circumferential p63 nuclear myoepithelial immunoreactivity. The adjacent LVI exhibited only focal endothelial CD31 immunoreactivity compared to regular lymphovascular channels where CD31 membrane immunoreactivity was circumferentially strong and nuclear p63 absent. A minority of the LVI channels exhibited dual p63 nuclear and CD31 membrane immunoreactivity within the endothelial lining but not within the same cell. In the experimental studies unlabelled breast carcinoma clumps, co‐injected with RFP‐human myoepithelial cells into GFP‐nude transgenics gave rise to tumor nodules of LVI exhibiting initially red fluorescence which was replaced by green fluorescence in the lining endothelial cells. When RFP‐murine embryonal stem cells substituted for the myoepithelial cells, the LVI lining cells exhibited persistent red fluorescence. These studies suggest that DCIS can progress to LVI by inducing a myoepithelial‐endothelial metaplasia. This metaplasia does not appear to involve direct myoepithelial‐endothelial transdifferentiation but rather a stem cell lineage switch.