Epithelial and Myoepithelial Biomarkers Expression and Risk of Subsequent Loco-Regional Relapses after Conservative Treatment of Ductal Carcinomas In Situ.
Alexandre Rouquette, Vanessa Gobeaux, Aurelie Cedenot, David Hajage, Nadege Gruel, Severine Alran, Brigitte Sigal-Zafrani, Youlia Kirova, Alain Fourquet, Anne Vincent-Salomon. Institut Curie, Paris, France
Background: The identification of biomarkers associated with risk of subsequent recurrence remains challenging for ductal carcinomas (DCIS) in situ treated with conservative surgery and radiation therapy. Our aims were to assess by immunohistochemistry the molecular subtypes, the stem cell, the proliferation epithelial cell and myoepithelial cell markers expression in a series of DCIS in order to evaluate the risk of relapse associated with these different biomarkers.
Design: The expression of ER, PR, ERBB2, CD44, CD24, ALDH1, KI67 (MIB1), p16, Aurora A and B, CD10, p63 were determined on DCIS tissue microarrays. For ER, PR and Ki67, 10%, for ERBB2 30% of positive cells were used as cut-off. The molecular subtypes were defined as luminal A: ER+ ERBB2- and Ki67<10%; luminal B: ER+, Ki67 >10% or ERBB2+; ERBB2 ER- and ERBB2 3+; triple negative: ER-PR- ERBB2-. The stem cell phenotype was defined as the co-expression of CD44+/CD24-/ALDH1+. Modifications of myoepithelial expression pattern were defined as the semi-quantitative evaluation of the presence and the positivity of myoepithelial cells with the analyzed marker compared to adjacent normal lobules (> or < 50%). All patients' charters were reviewed and clinical data recorded. All of the patients underwent tumorectomy followed by radiation therapy.
Results: The majority of the cases were ER (75%), PR (61%) positive. ERBB2 was +ve in 21% of the cases. KI67, p16, Aurora A and B were positive in 34%, 89%, 7% and 5.4% of the cases, respectively. A total of 55 cases were defined as luminal A (50%), 36 cases as luminal B (33%), 13 cases as ERBB2 and 3 cases were triple negative. The majority of the cases was CD44 +ve (96%), CD24 +ve (53%) and ALDH1 –ve (93%). Less than 50% of myoepithelial cells were present and positive with CD10 and p63 in 19 and 43% of the cases, respectively. At 10 years, 9 patients presented a relapse. No statistically significant link was observed between molecular subtypes, proliferation markers, the stem cell phenotype defined as CD44+/CD24-/ALDH1+, the myoepithelial cell modifications and a risk of relapse.
Conclusions: DCIS were in majority of luminal types (A: 50% or B: 33%) and few cases were basal-like. Myoepithelial cell density around DCIS lesions frequently decreased. In contrast to what has been proposed for DCIS treated by surgery alone, in this retrospective small series, DCIS treated by surgery and radiotherapy, no epithelial nor myoepithelial cell marker could help to identify cases associated with the higher risk of relapse.
Monday, February 28, 2011 1:00 PM
Poster Session II # 43, Monday Afternoon