Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer.
Here, we determined the possible association of stromal caveolin-1 (Cav-1) levels with DCIS recurrence and/or progression to invasive breast cancer. An initial cohort of 78 DCIS patients with follow-up data was examined. As ER-positivity was associated with recurrence, we focused our analysis on this subset of 56 patients. In this group, we observed that DCIS progressed to invasive breast cancer in approximately 14% of the patient population (8/56), in accordance with an expected progression rate of 12-15%. Nearly ninety percent of DCIS patients (7/8) that underwent recurrence to invasive breast cancer had reduced or absent levels of stromal Cav-1. Remarkably, an absence of stromal Cav-1 (score = 0) was specifically associated with early disease progression to invasive breast cancer, with reduced time to recurrence and higher recurrence rate. All DCIS patients with an absence of stromal Cav-1 underwent some form of recurrence (5/5) and the majority (4/5) underwent progression to invasive breast cancer. This represents an overall cumulative incidence rate of 100% for recurrence and 80% for progression. An absence of stromal Cav-1 in DCIS lesions was also specifically associated with the presence of inflammatory cells. Conversely, ninety-seven percent of ER(+) DCIS patients (35/36) with high levels of stromal Cav-1 (score = 2) did not show any invasive recurrence over the duration of follow-up (4-208 mo), and 89% of such patients are estimated to remain free of invasive recurrence, even after 15 y. Thus, determination of stromal Cav-1 levels may be a useful new biomarker for guiding the treatment of ER(+) DCIS patients.
Witkiewicz
Agnieszka K
AK
Stem Cell Biology and Regenerative Medicine Center, Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USA. agnieszka.witkiewicz@jefferson.edu
Dasgupta
Abhijit
A
Nguyen
Katherine H
KH
Liu
Chengbao
C
Kovatich
Albert J
AJ
Schwartz
Gordon F
GF
Pestell
Richard G
RG
Sotgia
Federica
F
Rui
Hallgeir
H
Lisanti
Michael P
MP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D051242:Caveolin 1 / Q000096:biosynthesis*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D051242:Caveolin 1