Oncoprotein HCCR-1 expression in breast cancer is well correlated with known breast cancer prognostic factors including the HER2 overexpression, p53 mutation, and ER/PR status

Abstract

Background: Oncoprotein HCCR-1 functions as a negative regulator of the p53 and contributes breast tumorigenesis. The serum HCCR-1 assay is useful in diagnosing breast cancer and mice transgenic for HCCR developed breast cancers. But it is unknown how HCCR-1 contributes to human breast tumorigenesis.

Methods: Oncogene HCCR-1 expression levels were determined in normal breast tissues, breast cancer tissues and cancer cell lines. We examined whether HCCR-1 protein expression in breast cancer is related to different biological characteristics, including ER, PR, p53 genotype, and HER2 status in 104 primary breast cancer tissues using immunohistochemical analyses.

Results: HCCR-1 was upregulated in breast cancer cells and tissues compared with normal breast tissues. In this study, overexpression of HCCR-1 was well correlated with known breast cancer prognostic markers including the presence of steroid receptors (ER and PR), p53 mutation and high HER2 overexpression. HCCR-1 was not detected in the ER-negative, PR-negative, p53 negative and low HER2 breast cancer tissues. These data indicate that the level of HCCR-1 in breast cancer tissues is relatively well correlated with known breast cancer factors, including the HER2 overexpression, p53 mutation, and ER/PR status.

Conclusion: Determination of HCCR-1 levels as options for HER2 testing is promising although it needs further evaluation.

Figure 1

HCCR-1 expressions in breast cancers. Northern analyses of HCCR-1 in human breast tissues and cell lines. Comparison of HCCR-1 mRNA expressions in breast cancer cell lines (BT-474, MCF-7 and MDA-MB-231), and fresh primary breast cancer tissues (C) and their corresponding normal counterparts (N). Human β-actin cDNA was used as a control probe (bottom panel).

Figure 2

HCCR-1 is positively well correlated with breast cancer prognostic parameters. Correlation of HCCR-1 expression levels with known breast cancer prognostic parameters. Immunohistochemical staining for ER, PR, HER2, p53 and HCCR-1 in fresh frozen tissues from human breast cancers. All the breast cancer tissues were derived from pathologically-proven invasive ductal carcinomas. Positive immunostaining for ER, PR, and p53 in the nuclei of carcinoma cells and for HCCR-1 in the cytoplasm of carcinoma cells (top panel). The HER2 immunohistochemical staining showing complete strong membrane staining (3+) in the carcinoma cells (top panel). Negative immunostaining for ER, PR, p53, HER2 and HCCR-1 in breast carcinoma (bottom panel). Original magnification, × 100.