Immunohistochemical Expression of ID4 in Triple Negative Breast Cancer Correlates with Basal Phenotype and Poorer Disease Free Survival
Puay Hoon Tan, Aye Aye Thike, Minn Minn Myint Thu, Murasaki Daniels, Poh Yian Cheok. Singapore General Hospital, Singapore
Background: Triple negative (TN) breast cancers are defined by the absence of estrogen receptor (ER), progesterone receptor (PR) and c-erbB2 expression. Oncologic management options for this group of aggressive tumors are limited. ID4, inhibitor of differentiation 4, is involved in cell proliferation and growth via negative regulation of helix-loop-helix transcription factors. ID4 has been reported to be upregulated in basal-like breast cancer. In this study, we evaluate the relationship of protein expression of ID4 with the basal-like phenotype and clinical outcome of TN breast cancer.
Design: The cohort comprised 699 TN breast cancers diagnosed between 1994 to 2010, to which antibodies to basal markers (CK14, 34βE12, EGFR) and ID4 were applied to sections cut from tissue microarray blocks, using the streptavidin-biotin method. Positive ID4 was defined as staining of 1% or more of tumor cell nuclei. Follow-up was obtained from casenotes. DFS (disease free survival) and OS (overall survival) were defined as time from diagnosis to recurrence or death respectively, and correlated with protein immunohistochemical expression. A p value <0.05 defined statistical significance.
Results: Median age was 52 years. Majority (83%) were Chinese, 8% Malay, 5% Indian, and 4% of other ethnic origins. Tumor size ranged from 0.9 to 20 cm (mean 3.6 cm, median 3 cm). Infiltrative ductal carcinoma was the commonest subtype (92%). Histologic grade 3 tumors predominated (77%). Node positivity occurred in 40%. CK14, 34βE12 and EGFR confirmed 85% to be basal-like. ID4 was expressed in 95% of cases. There was a statistically significant association of ID4 with histologic grade (p<0.001) and basal-like expression (p<0.001). Mean and median follow-up was 101 and 97 months respectively. Recurrences occurred in 29% and deaths in 24% of women. DFS was significantly reduced in ID4 positive TN breast cancer (p=0.046). There was no impact on OS.
Conclusions: ID4 appears to have a role in basal-like TN breast cancer, including a negative impact on DFS. Its mode of action likely involves transcription factors relating to cellular proliferation and growth. Investigating its relationship with other biological markers like p53 and BRCA which tend to disclose abnormal expression in TN breast cancer can lend additional insight into this group of challenging tumors. Its potential as another possible therapeutic target remains to be further elucidated.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 33, Wednesday Morning