Different Patterns of Stem Cell-Related Markers Expression between Luminal B and Invasive Micropapillary Carcinoma of the Breast.
Nadege Gruel, Aurelie Cedenot, Marion Richardson, Paul Freneaux, Fabien Reyal, Alain Fourquet, Paul Cottu, Xavier Sastre-Garau, Thierry Dubois, Olivier Delattre, Anne Vincent-Salomon. Institut Curie, Paris, France
Background: Stem cell markers expression in molecular subtypes of breast cancer have been studied but their expression in histological subtypes of breast cancers remains to be assessed. Invasive micropapillary carcinomas (IMPC) are recognized as being part of luminal B tumors. Our aims were to assess the expression of stem cells markers in this special subtype of breast carcinomas and to compare it to that of luminal A and B carcinomas.
Design: We analysed by immunohistochemistry the expression of stem cell-like markers CD44 and ALDH1, of CD24 marker of luminal differentiation, ER, PR and ERBB2 in 28 cases of IMPC. Invasive ductal carcinoma (IDC) (30 cases luminal A (ER+ve and 29 grade I and 1 grade II with low mitotic index; 36 cases luminal B, ER+ve and grade III, ERBB2 3+) were chosen as controls. CD44 and CD24 were evaluated on serial tissue sections. The cut-off was > 10% of positive cells for CD44, CD24, ALDH1, ER and PR, >30% for ERBB2. CD24 positivity was also evaluated at the apical (A) and the latero-basal membranes and the cytoplasm (C). As stem cells are frequently defined as being CD44+/CD24-, we evaluated the number of cases that demonstrated this combined phenotype.
Results: The majority of the IMPC were grade II (64%), ER+ve (92%), PR+ve (80%) and 25 % of the cases were ERBB2 +ve. Therefore, a majority of IMPC were luminal B carcinomas (grade II with a mitotic score of 2 or 3 and / or ERBB2 3+). IMPC showed 27/28 (96%), 22/28 (79%) and 1/28 (4%) positive cases for CD24, CD44 and ALDH1 respectively. Luminal A showed 22/30 (73%), 27/30 (90%) and 0/30 (0%) positive cases for CD24, CD44 and ALDH1 respectively. Luminal B showed 31/36 (86%), 26/36 (72%), 1/36 (3%) positive cases for CD24, CD44 and ALDH1 respectively. Strikingly, 23 out of the 27 (85%) CD24+ve IMPC presented an inverted apical staining contrasting with only 11 out of the 22 (50%) CD24+ve luminal A (p= 8.10-3), 4 out of the 31 (13%) luminal B (p= 4.10-8) CD24+ve cases. No statistical difference was observed for CD44 labeling between luminal A, B and IMPC. No IMPC case was CD44+/CD24-. In contrast, 12 luminal cases (8 and 4 cases of luminal A and B) presented this phenotype (p=1.6.10-2).
Conclusions: IMPC belong to the molecular luminal B group of tumors but harbor a different pattern of stem cell-like markers expression with a significantly higher rate of CD24 posivity at the inside-out apical membrane than the luminal A and B carcinomas with well oriented apical membrane and no CD44+/CD24- positive cells. This phenotype could participate to the specific pattern of IMPC.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 7, Tuesday Afternoon