Abstract P4-06-11: HER2 type DCIS acquires histological diversity by p53 mutation
Authors: Kamio M , Nogi H , Mimoto R , Imawari Y , Kato K , Uchida K , Takeyama H 
Published: August 2014

[Introduction]

It is widely known that breast cancer is a heterogeneous disease of various phenotypes and biological characteristics.

Several studies have identified distinct subtypes of invasive ductal carcinoma by gene expression profiling or staining pattern of estrogen receptor (ER), progesterone receptor (PR), and HER2/neu protein.

Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer, and is thought to be the precursor of invasive breast cancer.

One of the most well-known hypothesis shows that breast cancer occurs in a normal terminal duct lobular unit, and a histological continuity exists between the precursor and breast cancer.

The aim of this analysis is to reveal how DCIS acquires histological diversity and progresses to invasive ductal carcinoma.

We hypothesized that p53 gene mutation is responsible for this acquisition of histological diversity, and performed immunohistochemical analysis to pursue this hypothesis.

[Material and methods]

The participants of this study were taken from a database established by Jikei University School of Medicine. Between the period of April 2000 and April 2011, 84 cases of pure DCIS patients underwent operation.

Patients were classified into 4 subtypes by a combination of hormone receptor (HR) status and HER2 status.

The status of ER, PR, HER2, and p53 was determined by immunohistochemical staining.

Tumors with Allred score above 2 ER / PR nuclear staining were classified as ER / PR positive. Tumors with HER2 membranous staining equivalent to 3+ intensity with Hercep test in more than 30% of the cells were scored as overexpression. p53 was defined as positive when nuclear staining was equal to or greater than 10%.

We evaluated histological nuclear atypia to assess histological diversity of DCIS. When DCIS included different type of atypia cells more than 10%, we judged the histological diversity as positive.

[Results]

Patient characteristics are presented in table1.

Patient characteristics number%Age  median (range)55 (31-83)    Receptor status  ER / PR  positive6780negative1720HER2  positive1821negative6679   Subtype  HR+ / HER2-6274HR+ / HER2+56HR- / HER2+1315HR- / HER2-45

The classifications by the immunohistochemical subtype of DCIS are as follows: HR+/HER2- 62 cases (74%), HR+/HER2+ 5 cases (6%), HR-/HER2+ 13 cases (15%), HR-/HER2- 4 cases (5%).

p53 expression in HR-/HER2+ and HR-/HER2- subtype was significantly higher than HR+/HER2- and HR+/HER2+ subtype (p&lt;0.001).

The frequency of histological diversity by nuclear atypia was high in HR+/HER2- and HR-HER2+ subtype (p = 0.009).

In HR-HER2+ subtype, p53 expression was associated with histological diversity (p = 0.021). But in HR-HER2+ subtype, there was no association with p53 expression and histological diversity.

p53 status and histological diversity of DCIS HR+/HER2-HR+/HER2+HR-/HER2+HR-/HER2-pp53     positive5193&lt;0.001negative57441       histological diversity     positive481910.009negative14443       p0.3310.5760.0210.501 

[Conclusion]

This analysis demonstrates that HR-HER2+ subtype DCIS acquires histological diversity by p53 mutation.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-06-11.