Breast Carcinoma of Combined Histologic Grade 2: Prognostic Significance of Immunohistochemical Features
J Laforga, FI Aranda, M Niveiro, T Muci, J Segui, A Paya, G Peiro. Hospital of Denia, Denia, Alicante, Spain; Universitary General Hospital, Alicante, Spain
Background: When breast cancer (BC) is graded by the Nottingham system, an important proportion of the cases are classified into the category of grade 2 (G2), irrespective of the immunophenotype. In order to determine some discriminating features with prognostic significance, we analyzed the expression of Bcl2, Estrogen and Progesterone receptors (ER/PgR), Ki67, Her2 and p53 in a series of BC of G2.
Design: A total of 811 cases of invasive BC were studied from our database. Median clinical follow-up was 78 months (range 15 to 313 months). According to the Nottingham system, 292 cases (36%) were G2. Ages ranged from 20 to 86 years (median 57 years). Tumor size ranged from 2 to 110 mm (median 19 mm). Immunohistochemical (IHC) staining was performed for Bcl2 (cut-of 50%), ER (cut-of 10%), PgR (cut-off 10%), Ki67 (cut-off 15%), p53 (cut-off 20%) and Her2 (2+ and <30% 3+ confirmed by FISH). Tumors were classified according to the immunophenotype as luminal low-risk (Ki67/p53 <20%), luminal high-risk (Ki67/p53 >20%), Her2-positive and triple-negative (ER/PR/Her2-negative). Significant associations were identified using Chi-square and Fisher's exact test. Actuarial survival was calculated by the Kaplan-Meier method (log rank test). Multivariate analysis was determined by Cox's proportional hazard model. A p-value <0.05 was considered significant.
Results: Tumors were predominantly of ductal type (93 %), with <20 mm in size (56%) and negative lymph nodes (66%). Bcl2 was high in 67% cases, ER-positive in 84%, PgR-positive in 76%, low Ki67 in 64%, p53-negative in 86% and Her2-positive in 15%. Based on IHC findings, 64% tumors were classified as luminal low risk, 14% as luminal high risk, 15% HER2-positive and 7% as triple negative. Survival analysis showed a significant correlation with axillary lymph node status (p=0.01), Bcl2 (p=0.01), Ki67 (p=0.04) and immunophenotype (p=0.04). However, there was no association with tumor size, ER/PgR or p53 (all p>0.05). Moreover, a multivariate analysis showed that the lymph node status was the only significant independent predictor of survival (p=0.023).
Conclusions: In our series of BC of G2, the results show that the stratification of the tumors according to their immunophenotype and the levels of Bcl2 and Ki67 have clinical relevance for those patients. However, the axillary lymph node status is the only independent prognostic factor.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 2, Tuesday Afternoon