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Research Paper

Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer

Agnieszka Witkiewicz, Abhijit Dasgupta, Katherine Nguyen, Chengbao Liu, Albert J. Kovatich, Gordon F. Schwartz, Richard G. Pestell, Federica Sotgia, Hallgeir Rui and Michael P. Lisanti

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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 ~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 months), and 89% of such patients are estimated to
remain free of invasive recurrence, even after 15 years. Thus, determination of stromal
Cav-1 levels may be a useful new biomarker for guiding the treatment of ER(+) DCIS
patients.

Authors

Agnieszka Witkiewicz

Stem Cell Biology and Regenerative Medicine Center; Department of Pathology, Jefferson Center for Pancreatic, Biliary and Related Cancers; Thomas Jefferson University, Philadelphia, PA,

Abhijit Dasgupta

Stem Cell Biology and Regenerative Medicine Center; Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics; Thomas Jefferson University; Philadelphia, PA;

Katherine Nguyen

Stem Cell Biology and Regenerative Medicine Center; Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics; Thomas Jefferson University; Philadelphia, PA;

Chengbao Liu

Stem Cell Biology and Regenerative Medicine Center; Kimmel Cancer Center, Departments of Cancer Biology and Medical Oncology; Thomas Jefferson University, Philadelphia, PA, 19107, USA

Albert J. Kovatich

MDR Global Systems, LLC., Windber, PA, 15963, US

Gordon F. Schwartz

Stem Cell Biology and Regenerative Medicine Center; Department of Surgery, Thomas Jefferson University, Philadelphia, PA, 19107, USA

Richard G. Pestell

Stem Cell Biology and Regenerative Medicine CenterThomas Jefferson University; Philadelphia, PA; Kimmel Cancer Center, Departments of Cancer Biology and Medical Oncology, Thomas Jefferson University, Philadelphia, PA, 19107, USA

Federica Sotgia

Stem Cell Biology and Regenerative Medicine Center; Kimmel Cancer Center, Departments of Cancer Biology and Medical Oncology; Thomas Jefferson University, Philadelphia, Pennsylvania

Hallgeir Rui

Stem Cell Biology and Regenerative Medicine Center; Kimmel Cancer Center, Departments of Cancer Biology and Medical Oncology; Thomas Jefferson University, Philadelphia, Pennsylvania

Michael P. Lisanti Corresponding author: michael.lisanti@kimmelcancercenter.org

Stem Cell Biology and Regenerative Medicine Center; Kimmel Cancer Center, Departments of Cancer Biology and Medical Oncology; Thomas Jefferson University, Philadelphia, Pennsylvania

This is an open-access article

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If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.