Abstract P5-16-05: Comparative analysis of the immunohistochemical profile of ductal carcinoma in situ to invasive ductal carcinoma
Authors: Orozco JIJ , Gago FE , Ciocca DR , Mendiondo BS , Ciocca LA , Ibarra MJ , Tello OM 
Published: August 2014

Introduction:

The molecular subtypes have classified invasive breast carcinomas in diverse entities with different clinical behaviors, but the prevalence of these subtypes in ductal carcinoma in situ (DCIS) has not been evaluated in detail. The main objectives of this study were to compare proteomic expression profiles of DCIS and invasive ductal carcinoma (IDC) by immunohistochemistry (IHC), classify them according to the molecular subtypes and evaluate the relationship between the expression of the biological markers and the tumoral grade.

Methods:

We assessed the frequency of expression of ER, PR, HER2, proliferation markers (PCNA or Ki67), Bcl-2 and p53 in 107 DCIS and compared them with the expression of 682 IDC. They were classified according to molecular subtypes. We evaluated the relationship between the expression of these markers and the nuclear and histological grades of DCIS and IDC respectively.

Results

The expression of Bcl-2 and PR was significantly more frequent in the DCIS group (p = 0.0461 and p = 0.0001 respectively). The IDC showed significantly increased values for cell proliferation markers and mutated p53 (p &lt; 0.0001 and p = 0.0062 respectively). The prevalence of ER and HER2 was similar in both groups (p = 0.0912 and p = 0.4686 respectively).

Clinico-pathological parameters and biomarkers expression DCISIDCPN107682 Age (mean)52.75 years55.79 years0.0219Tumoral size (mean)1.62 cm2.23 cm&lt;0.0001Grade 144 (41.12%)95 (13.92%)&lt;0.0001Grade 229 (27.10%)277 (40.61%)0.0076Grade 334 (31.78%)310 (45.45%)0.0086ER positive82 (76.63%)467 (68.47%)0.0912PR positive70 (65.42%)373 (54.69%)0.0461HER2 positive19 (17.78%)101 (14.81%)0.4686Proliferation markers high65 (60.75%)206 (30.21%)&lt;0.0001Bcl-2 positive84 (78.51%)405 (59.38%)0.0001p53 mutated33 (30.84%)307 (45.01%)0.0062

The luminal A subtype was more common in DCIS (p = 0.0003), whereas luminal B no-HER2 and triple negative were more prevalent in IDCs (p = 0.0195 and p = 0.0351 respectively). There were no differences in the frequency of luminal B-HER2 and HER2 positives (p = 0.3279 and p = 1.0000 respectively).

Prevalence of molecular subtypes. DCISIDCPLuminal A46 (43%)172 (25.22%)0.0003Luminal B32 (29.91%)288 (42.23%)0.0195Luminal B-HER2+11 (10.28%)50 (7.33%)0.3279HER28 (7.47%)51 (7.48%)1.0000Triple Negative10 (9.34%)121 (17.74%)0.0351

In relation to nuclear grade of DCIS, no differences were detected with respect to the expression of ER, Bcl-2 and mutated p53 (p = 0.3691, p = 0.8136 and p = 0.3138 respectively). Proliferation markers increased significantly with increasing nuclear grade (p &lt;0.0001). PR was mostly expressed in DCIS grade 1 and HER2 in grade 3, but this was not statistically significant (p = 0.0741 and p = 0.0851 respectively). With regard to histological grade of IDCs, there were a higher frequency of ER, PR, Bcl-2 in grades 1 (p &lt;0.0001). G3 carcinomas showed increased expression of HER2, proliferation markers and mutated p53 (p &lt;0.0001, p &lt;0.0001 and p = 0.0110 respectively).

Conclusions:

The DCIS presents significant differences in tumor subtypes compared with IDC. The lower frequency of triple negative tumors and Luminal B-HER2-, lower expression of mutated p53 and lower degree of proliferation, suggest a less aggressive behavior of DCIS.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-16-05.