Low CD10 mRNA expression identifies high-risk ductal carcinoma in situ (DCIS).
OBJECTIVE
Optimal management of breast ductal carcinoma in situ (DCIS) is controversial, and many patients are still overtreated. The local death of myoepithelial cells (MECs) is believed to be a pre-requisite to tumor invasion. We thus hypothesized that loss of CD10 expression, a MEC surface peptidase, would signify basement membrane disruption and confer increased risk of relapse in DCIS. The aim of our study was to retrospectively evaluate the prognostic value of CD10 in DCIS.


METHODS
CD10 expression was evaluated by quantitative RT-PCR and immunohistochemistry using paraffin-embedded samples of normal breast tissue (n = 11); of morphologically normal ducts associated with DCIS (n = 10); and of DCIS without an invasive component (n = 154).


RESULTS
CD10 immunostaining was only observed in MECs in normal tissue and in DCIS. Normal tissue showed high mRNA expression levels of CD10, whereas DCIS showed a variable range. After a median follow-up of 6 years, DCIS with CD10 expression below the levels observed in normal tissue (71%) demonstrated a higher risk of local relapse (HR = 1.88; [95CI:1.30-2.70], p = 0.001) in univariate analysis. No relapse was observed in patients expressing high CD10 mRNA levels (29%) similar to the ones observed in normal tissue. In multivariate analysis including known prognostic factors, low CD10 mRNA expression remained significant (HR = 2.25; [95%CI:1.24-4.09], p = 0.008), as did the recently revised Van Nuys Prognostic Index (VNPI) score (HR = 2.03; [95%CI:1.23-3.35], p = 0.006).


CONCLUSIONS
The decrease of CD10 expression in MECs is associated with a higher risk of relapse in DCIS; this knowledge has the potential to improve DCIS management.
Toussaint
Jérôme
J
Breast Cancer Translational Research Laboratory JC Heuson, Jules Bordet Institute, Brussels, Belgium.
Durbecq
Virginie
V
Altintas
Sevilay
S
Doriath
Valérie
V
Rouas
Ghizlane
G
Paesmans
Marianne
M
Bedard
Philippe
P
Haibe-Kains
Benjamin
B
Tjalma
Wiebren A
WA
Larsimont
Denis
D
Piccart
Martine
M
Sotiriou
Christos
C
D000328:Adult; D001940:Breast / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D015260:Neprilysin / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D012333:RNA, Messenger; D015260:Neprilysin