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Int J Clin Exp Pathol 2(5),444-455;2009

Original Article
Prevalence, Morphologic Features and Proliferation Indices of Breast Carcinoma
Molecular Classes Using Immunohistochemical Surrogate Markers

Rohit Bhargava, Joan Striebel, Sushil Beriwal, John C. Flickinger, Agnieszka Onisko, Gretchen Ahrendt and David J. Dabbs

Departments of Pathology, Radiation Oncology and Surgery, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh,

Received 01 February 2009; Accepted and available online 09 February 2009

Abstract: There is dearth of studies that provide a practical working formulation of breast cancer gene expression analysis for the surgical
pathologist. ER, PR, HER2 were used as surrogate markers to classify 205 breast carcinomas into molecular classes. Ki-67 labeling index
was calculated using an image analysis system. The data was analyzed for molecular class prevalence, and inter-relationships amongst
morphologic parameters, Ki-67 index, and molecular classes. Of the 205 tumors, 113 (55%) were classified as luminal A (strong ER+, HER2
negative), 34 (17%) as luminal B (weak to moderate ER+, HER2 negative), 32 (15%) as triple negative (negative for ER/PR and HER2), 8 (4%)
as ERBB2 (negative for ER/PR but HER2+), 10 (5%) as luminal A-HER2 hybrid (strong ER+ and HER2+), and 8 (4%) as luminal B-HER2 hybrid
(weak to moderate ER+ and HER2+). The average Ki-67 index was lowest in luminal A (15.8%), intermediate for ERBB2 (27.8%) and highest
for triple negative tumors (>50%). Multivariate logistic regression analyses found the following associations: ERBB2 tumors with apocrine
differentiation (p=0.0031); Triple negative tumors with high Ki-67 index (p<0.0001) and CK5 positivity (p<0.0001); HER2 negative-low receptor
positive tumors (luminal B) with increased lymph node involvement (p=0.0141). The immunohistologic criteria were validated on a different set
of 359 cases treated with neoadjuvant chemotherapy, which showed a pathologic complete response predominantly in ERBB2 and triple
negative tumors. Immunohistochemistry is a reliable surrogate tool to classify breast carcinoma according to the gene expression profile
classification. (IJCEP902001).

Key Words: Molecular classes, breast carcinoma, immunohistochemical surrogate markers, Ki-67

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Address all correspondence to: Rohit Bhargava, MD, Department of Pathology, Magee-Womens Hospital, 300 Halket Street, Pittsburgh PA
15213, USA. Tel: 1-412-641-4641; Fax: 1-412-641-1675; Email: