Human Epididymis Protein 4 (HE4)

Gender	Range (pmol/L)
Male	Not Established
Female
Age
0 to 39 years	0.0 – 61.2
40 to 49 years	0.0 – 63.6
50 to 59 years	0.0 – 105.2
60 to 69 years	0.0 – 96.5
>69 years	0.0 – 96.9

The distribution of HE4 levels determined in 1147 specimens is shown in the table.
Distribution of HE4 Assay Values

Apparently Healthy
Female (premenopausal)
Number of Subjects	76
0−150 pMol	72
150.1−300 pMol	3
300.1−500 pMol	0
>500 pMol	1
Female (postmenopausal)
Number of Subjects	103
0−150 pMol	97
150.1−300 pMol	5
300.1−500 pMol	0
>500 pMol	1
Benign Conditions
Pregnancy
Number of Subjects	22
0−150 pMol	21
150.1−300 pMol	1
300.1−500 pMol	0
>500 pMol	0
Benign gynecological disease
Number of Subjects	347
0−150 pMol	324
150.1−300 pMol	18
300.1−500 pMol	1
>500 pMol	4
Other benign disease
Number of Subjects	108
0−150 pMol	82
150.1−300 pMol	8
300.1−500 pMol	7
>500 pMol	11
Hypertension/CHF
Number of Subjects	96
0−150 pMol	75
150.1−300 pMol	16
300.1−500 pMol	2
>500 pMol	3
Cancer
Ovarian cancer
Number of Subjects	127
0−150 pMol	27
150.1−300 pMol	18
300.1−500 pMol	21
>500 pMol	61
Breast cancer
Number of Subjects	46
0−150 pMol	40
150.1−300 pMol	4
300.1−500 pMol	2
>500 pMol	0
Lung cancer
Number of Subjects	50
0−150 pMol	29
150.1−300 pMol	15
300.1−500 pMol	6
>500 pMol	0
Endometrial cancer
Number of Subjects	116
0−150 pMol	86
150.1−300 pMol	15
300.1−500 pMol	4
>500 pMol	11
Gastrointestinal cancer
Number of Subjects	56
0−150 pMol	47
150.1−300 pMol	8
300.1−500 pMol	0
>500 pMol	1

Distribution of HE4 Assay Values

	Number of Subjects	0−150 pMol	150.1−300 pMol	300.1−500 pMol	>500 pMol
Apparently Healthy
Female (premenopausal)	76	72	3	0	1
Female (postmenopausal)	103	97	5	0	1
Benign Conditions
Pregnancy	22	21	1	0	0
Benign gynecological disease	347	324	18	1	4
Other benign disease	108	82	8	7	11
Hypertension/CHF	96	75	16	2	3
Cancer
Ovarian cancer	127	27	18	21	61
Breast cancer	46	40	4	2	0
Lung cancer	50	29	15	6	0
Endometrial cancer	116	86	15	4	11
Gastrointestinal cancer	56	47	8	0	1

*In this study, 94.4% of the healthy female subjects had an HE4 assay value ≤150 pMol.
Monitoring of disease status in patients diagnosed with ovarian cancer.
The effectiveness of the HE4 EIA as an aid in monitoring of disease status in ovarian cancer patients was determined by assessing changes in HE4 levels in serial serum samples from 80 patients compared to changes in disease status. A study involving a total of 354 pairs of observations was undertaken with an average number of 4.4 observations per patient. A positive change in HE4 was defined as an increase in the value that was at least 25% greater than the previous value of the test. This level of change takes into account the variability of the assay and the biological variability. Sixty percent or 76/126 of the patient samples with a positive change correlated with the disease progression, while 75% or 171/228 of the patient serial samples with no significant change in HE4 value correlated with no progression. The total concordance was 70% or 247/354. The following table presents the data in a 2 x 2 format.
Change in Disease State per Sequential Pair

Increase in HE4 Concentration
>25%
Progression	76
No Progression	57
Total	133
≤25%
Progression	50
No Progression	171
Total	221
Total
Progression	126
No Progression	228
Total	354

Change in Disease State per Sequential Pair

Increase in HE4 Concentration	Progression	No Progression	Total
>25%	76	57	133
≤25%	50	171	221
Total	126	228	354

The following table shows the resulting sensitivities and specificities of the HE4 EIA compared to the disease status at various changes in HE4 EIA concentrations.
• Sensitivity is represented as a concordance of the HE4 EIA to progression of disease.
• Specificity is represented as a concordance of the HE4 EIA to no progression of disease.

Percent Change In HE4 Concentration (%)
10
Sensitivity (%)	71
Specificity (%)	62
25
Sensitivity (%)	60
Specificity (%)	75
50
Sensitivity (%)	43
Specificity (%)	88
75
Sensitivity (%)	38
Specificity (%)	92
100
Sensitivity (%)	31
Specificity (%)	95

Percent Change In HE4 Concentration (%)	Sensitivity (%)	Specificity (%)
10	71	62
25	60	75
50	43	88
75	38	92
100	31	95