[689] HER2 Copy Number in the Assessment of HER2 Status in Gastric/GOJ Cancers: Does It Matter?

Priyanthi Kumarasinghe, Bastiaan de Boer, Khor Sheng, Esther Ooi, Sureshika Jayasinghe, Stephen Fox. PathWest, QEII Medical Centre, Perth, WA, Australia; Massachusetts General Hospital, Boston, MA; Peter MacCallum Cancer Centre, St Andrews Place, Melbourne, VIC, Australia; University of Western Australia, Perth, WA, Australia

Background: Following the results of the ToGA study, combination chemotherapy with trastuzumab was approved to treat HER2 positive advanced/metastatic gastric & GOJ carcinomas. HER2 positivity was defined as either an IHC 3+ score or HER2 amplification as determined by HER2/Chr17 ratio ≥2.0 rather than the HER2 copy number (CN) per cell. Sub group analysis showed that there was no survival benefit for the HER2 amplified but IHC negative group (score 0 or 1+) which was ∼ 23% of the positive cohort. We aim to compare HER2 CN against HER2/Chr17 ratio in relation to the IHC score.
Design: HER2 status of gastric and GOJ cancers were assessed by IHC and silver in-situ hybridisation (SISH). IHC scoring (0-3+) was performed using "modified gastric" criteria. HER2 and Chr17 CNs were counted in at least in 20 cancer cells and the HER2:Chr17 ratio calculated as per protocol. These were compared to the IHC scores.
Results: There were 142 gastric & GOJ carcinomas.

IHC score vs HER2 copy numbers & ratio

IHC Score (No: of cases)	Mean CN	Range	Mean ratio	Range
0 (79)	2.6	1.3-4.7	1.2	0.7-2.0
1 (24)	2.7	1.7-5.1	1.3	0.9-2.6
2 (18)	4.5	1.8-15.0	1.8	0.9-5.3
3 (21)	20.1	3.6-32.0	10.2	1.3-16.0

CN=copy number

The HER2 CN & ratio for IHC score 3+ vs scores 2+, 1+ and 0 were significantly different (all p<0.001). The CN for IHC 2+ vs IHC 1+ and IHC 0 was significantly different (both p≤0.001) but the ratio was not. The CN and the ratio for scores 1 & 0 were not significantly different (p=0.6419). Using ToGA criteria 19% (27/142) were HER2 positive; 11%(3/27) did not show increase in CN; 7% (2/27) IHC negatives showed amplification by ratio, but the copy number was <6. An equivocal IHC score (2+) showed amplification in 4 of 18 (6%); 3 by both ratio & CN and one by ratio alone. An IHC score (3+) showed > 6 HER2 CNs and a ratio ≥2.0 in all but one case which showed no amplification by either CN or ratio (1/21).
Conclusions: Our findings show that the HER2 CN correlates better with the IHC score than the ratio. There was no survival benefit for IHC negative but amplified cases (∼ 23%) in the ToGA trial. This subgroup was smaller (7%) in our cohort and neither showed a copy number >6. HER2 CN appears to be a better measurement than the ratio in determining the amplification status in IHC equivocal and negative cases.
Category: Gastrointestinal

Monday, March 19, 2012 1:00 PM

Poster Session II # 92, Monday Afternoon