The Human Epidermal Growth Factor Receptor 2 Screening Tests for Breast Cancer Suggested by the New Updated Recommendation of the American Society of Clinical Oncology/College of American Pathologists Will Involve a Rise of the In-Situ Hybridization Tests for the European Laboratories of Pathology

Table 4

Example of FISH work overflow calculated for 1000 women.

Indications of the FISH test	2007 guidelines	2007 guidelines	2013 guidelines	2013 guidelines	2013 guidelines
	2+ IHC	2+ and 3+	2+	2+ and 3+	All cases
IHC 0+/1+	700	700	525	525	—	(1)
IHC 2+	180	180	274	274	—	(2)
IHC 3+	120	120	201	201	—	(3)
FISH +	36	36	43	236	236	(4)
Number of false-positive IHC 3+/1000 cases	0	0	8	0	—	(5)
Prevalence of HER2	15.6%	15.6%	24.4%	23.6%	23.6%
Number of IHC performed	1000	1000	1000	1000	0
Number of FISH tests performed	180	300	274	475	1000
Net FISH overwork with 2007 as reference (%) for FISH controlling 2+ IHC	0%	+66%	+52%	+163%	+455%
Net FISH overwork with 2007 as reference (%) for FISH controlling 2+ and 3+ IHC	−40%	0%	−8%	+58%	+233%

FISH work overflow calculations for 1000 women when we use the 2007 or the 2013 ASCO/CAP recommendations with HER2 FISH as control of 2+ IHC or 2+/3+ IHC (system used in some European countries). The last column illustrated a system of HER2 screening only based on HER2 FISH as used in the USA.
(1) For the 2007 system, 350 cases of 0+ IHC and 350 cases of 1+ IHC are based on the 69.8% of our 0/1+ IHC of our clinical data. Table 1 showed that 54/118 cases (about 50%) of 1+ became 2+ with the 2013 system, about 350 * 0.5 = 175 cases.
(2) Table 1 showed that 16/40 (40%) of the 2+ became 3+ for the 2013 system. For 1000 cases, 180×0.4=81 cases. For 2013 system, 180−81+175=274.
(3) For the 2013 system, 3+ are the sum of 120 cases of 3+IHC of the 2007 system and 81 cases of the 2+ IHC of the 2007 system that changes in 3+ IHC in the 2013 system. The total of 3+ IHC for the 2013 system is 201 cases.
(4) For the 2007 system, 20% of our 2+ are amplified (20/40) and, for 2013 system, 15.7% of 2+ are amplified (14/89).
In the column of 2013 guidelines of FISH for 2+ and 3+, 240 is calculated for 201 IHC 3+ − 8 false-positive cases (see 5) + 43 cases of 2+ IHC positive FISH.
(5) Table 1: 1/25 or 4% is the rate of false-positive rate for 3+ IHC of the 2013 system. For 1000 cases, there are 201 3+ IHC or 8 false-positive cases (201×0.4).