Her2

Her2 is a 185 kilodalton tyrosine kinase, a member of the human epidermal growth factor receptor family, which localizes to the cell membrane. It is encoded at 17q12-21.32.

FISH is the reference standard for assessing Her2 status but is technically difficult. The reproducibility and correlation of immunohistochemistry with FISH have been questioned. A bright field gold-facilitated autometallographic method (GOLDFISH) for detecting Her2 amplification holds promise of allowing FISH to be performed using immunohistochemical techniques¹.

Immunohistochemical expression

It is overexpressed in 20-30% of female breast cancers. In 90% of cases, this is secondary to gene amplification. Overexpression has also been reported in 90% of ductal carcinoma in situ. This implies that gene amplification may be lost in association with the development of invasive malignancy.

In one study, the rate of both amplification and immunoreactivity was concordant in the invasive and intraduct components of the same tumour, with lower rates of positivity in both (the invasive ductal carcinoma and the intraduct carcinoma in the presence of invasion) by comparison with pure ductal carcinoma in situ²:

reference 2		Gene amplification by FISH	Overexpression by immunohistochemsitry	rate by either method
Pure DCIS		25/50 nuclear grade 1: 5/12 (42%), nuclear grade 2: 7/15 (47%), nuclear grade 3: 13/23 (57%)	25/50	50%
Invasive ductal carcinoma	Intraduct component	81/270 (nuclear grade 1: 6/35 (17%), nuclear grade 2: 20/93 (22%), nuclear grade 3: 55/142 (39%)	81/270	30%
	Invasive component	77/270 (within the invasive component, amplification in the absence of overexpression occurred in 6 cases. 4 cases showed amplification in the intraduct but not the invasive component)	79/270 (within the invasive component, overexpression in the absence of amplification occurred in 8 cases)	29%

In the same study, the Her2 expresssion in lymph node metastases correlated well with that in the primary tumour, which is important to the rationale for the use of Herceptin for metastatic disease:

results by immunohistochemsitry2		Lymph node metastases
		negative	positive
Primary tumours	negative	79	3
	positive	5	29

Her2 does not appear to be commonly overexpressed in ovarian tumours.

Diagnostic utility

Her2 amplification predicts a poor prognosis, responsiveness to anthracycline-based chemotherapy and those cancers likely to respond to monoclonal antibody therapy against Her2 (Herceptin, trastuzumab). References

¹ Downs-Kelly E, Pettay J, Hicks D, et al. Analytical validation and interobserver reproducibility of EnzMet GenePro: a second-generation bright-field metallography assay for concomitant detection of HER2 gene status and protein expression in invasive carcinoma of the breast. Am J Surg Pathol 2005; 29:1505-11

² Park K, Han S, Kim HJ, et al. HER2 status in pure ductal carcinoma in situ and in the intraductal and invasive components of invasive ductal carcinoma determined by fluorescence in situ hybridization and immunohistochemistry. Histopathology 2006; 48:702-7

³ Bartkova J, Barnes DM, Millis RR, et al. Immunohistochemical demonstration of c-erbB-2 protein in mammary ductal carcinoma in situ. Hum Pathol 1990; 21:1164-7

This page last revised 21.1.2006.

©SMUHT/PW Bishop