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Production and Performance Evaluation of External Quality Assessment Materials for Human Epididymis Protein 4 Assay
J Lab Med Qual Assur 2019;41:153-160
Published online September 30, 2019
© 2019 Korean Association of External Quality Assessment Service.

Anna Lee and Hee-Jung Kim

Department of Laboratory Medicine, Seoul Clinical Laboratories, Yongin, Korea
Correspondence to: Anna Lee
Department of Laboratory Medicine, Seoul Clinical Laboratories, 23F, Heungdeok IT valley, 13 Heungdeok 1-ro, Giheung-gu, Yongin 16954, Korea
Tel: +82-2-330-2012 Fax: +82-2-790-6509 E-mail: anlee@scllab.co.kr
Received June 8, 2019; Revised July 5, 2019; Accepted July 8, 2019.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract

Background:

External quality assessment (EQA) is important for standardizing cancer biomarker assays, thereby, ensuring accurate and precise results. Although the human epididymis-specific protein 4 (HE4) assay has been increasingly used to detect and monitor ovarian malignancy in Korea, a nation-wide EQA program for HE4 has not been appropriately established. To conduct an EQA program, a large amount of quality control (QC) materials are required. This study aimed to produce HE4 QC materials for an EQA program and evaluate their homogeneity and stability.

Methods:

QC materials for three different concentrations of HE4 were produced from the collected remnant sera of 275 patients for whom the HE4 assays were performed. These materials were evaluated for homogeneity between vials and stability during storage. The frozen QC materials were distributed to 13 representative organizations for a provisional EQA.

Results:

The total coefficient of variation of the HE4 QC materials of three concentrations was 0.75%–1.24%, and no significant differences were noted between vials; therefore, the samples were considered to be homogenous. With respect to stability, the HE4 QC materials were found to be stable till 30 days when frozen and for 24 hours when refrigerated. The results of the provisional HE4 EQA were reviewed and the survey results were reported to each participant.

Conclusions:

The HE4 QC materials produced from remnant specimens were found to be homogenous between vials and stable in a frozen condition until 30 days. The findings of this study may be practically applied for establishing a future HE4 EQA program.

Keywords : Human epididymis-specific protein 4, Ovarian neoplasms, External quality assessment, Quality control
꽌濡

2016뀈 援媛븫벑濡앺넻怨꾩뿉 쓽븯硫 援궡 궃냼븫쓽 쑀蹂 쁽솴 뿬꽦뿉꽌 諛쒖깮븯뒗 쟾泥 븫醫낆쓽 2.0%瑜 李⑥븯硫, 議곗쑀蹂묐쪧 씤援 100,000紐낅떦 76.3紐낆쑝濡 뿬꽦뿉꽌 諛쒖깮븯뒗 븫醫 以 8踰덉㎏濡 넂떎[1]. 궃냼븫 珥덇린뿉뒗 臾댁쬆긽씤 寃쎌슦媛 遺遺꾩씠怨, 利앹긽씠 엳뜑씪룄 鍮꾪듅씠쟻誘濡 뼇꽦吏덊솚怨 媛먮퀎씠 뼱젮썙 70% 씠긽쓽 궃냼븫씠 吏꾪뻾맂 긽깭뿉꽌 諛쒓껄맂떎. 궃냼븫 I-II湲곗뿉 議곌린 諛쒓껄 떆 5뀈 깮議댁쑉씠 80%-90%濡 넂쑝굹, 蹂묎린媛 吏꾪뻾릺뼱 III-IV湲곗뿉 諛쒓껄릺뒗 寃쎌슦 깮議댁쑉씠 30%濡 궙쑝誘濡[2], 궃냼븫쓽 議곌린吏꾨떒 깮議댁쑉 뼢긽뿉 留ㅼ슦 以묒슂븯떎.

궃냼븫쓣 吏꾨떒븯湲 쐞븳 寃궗踰뺤쑝濡쒕뒗 怨⑤컲珥덉쓬뙆 삁泥 cancer antigen 125 (CA-125) 寃궗媛 二쇰줈 씠슜릺뼱 솕떎. 씤媛꾨怨좏솚떒諛4 (human epididymis protein 4, HE4)뒗 CA-125 蹂댁셿쟻쑝濡 궃냼븫쓽 議곌린 吏꾨떒 諛 옱諛 뿬遺 솗씤쓣 쐞븳 寃궗濡 媛쒕컻릺뼱 2011뀈 誘멸뎅 Food and Drug Administration (FDA)濡쒕꽣 뿀媛瑜 諛쏆븯떎[3]. 援궡뿉꽌룄 洹 븞쟾꽦怨 쑀슚꽦뿉 빐 2014뀈 2썡 21씪 떊쓽猷뚭린닠룊媛 怨좎떆(蹂닿굔蹂듭遺 怨좎떆 젣2014-32샇)媛 怨듯몴릺뿀쑝硫, 씠썑 援궡뿉꽌 HE4 寃궗쓽 궗슜씠 湲됱쬆븯怨 엳떎. 삉븳 2016뀈 11썡 1씪 HE4 寃궗뿉 븳 슂뼇湲됱뿬 쟻슜씠 怨좎떆릺뿀怨(굹-437 C4370), 蹂댄뿕떖궗룊媛썝 蹂닿굔쓽猷뚮퉭뜲씠꽣떆뒪뀥뿉 쓽븯硫 2017뀈 븳빐 泥援щ맂 HE4 뿰媛 珥 궗슜웾 67,084嫄댁쑝濡 HE4 寃궗쓽 援궡 궗슜웾씠 吏냽쟻쑝濡 利앷븯怨 엳떎(Fig. 1). 寃泥 寃궗 쟾臾멸린愿씤 蹂 寃궗떎뿉 쓽猶곕릺뒗 HE4 寃궗웾 삉븳 理쒓렐 닔뀈 궗씠뿉 湲됱쬆븯怨 엳쑝硫(Fig. 2), 2018뀈 湲곗, HE4 寃궗쓽 뿰媛 寃궗 嫄댁닔뒗 湲곗〈 궃냼븫 醫낆뼇몴吏옄濡 媛옣 留롮씠 궗슜릺뒗 CA-125 뿰媛 寃궗 嫄댁닔쓽 빟 28.3%瑜 李⑥븯떎. 뵲씪꽌 HE4 寃궗뒗 궃냼븫 吏꾨떒 諛 移섎즺 썑 異붿쟻쓣 쐞븳 寃궗濡쒖꽌 뼢썑 洹 엫긽쟻 슂援щ룄媛 뜑슧 利앷븷 寃껋쑝濡 깮媛곷맂떎.

誘멸뎅쓽 College of American Pathologists (CAP) 二쇨 젙룄愿由ы봽濡쒓렇옩뿉뒗 HE4 寃궗뿉 븳 survey媛 2017뀈遺꽣 떊꽕릺뼱 슫슜릺怨 엳떎. 븯吏留 援궡뿉뒗 HE4 寃궗뿉 븳 떊鍮숇룄議곗궗봽濡쒓렇옩씠 븘吏 留덈젴릺뼱 엳吏 븡븘 HE4 寃궗쓽 쇅遺젙룄愿由ъ뿉 뼱젮씠 엳떎. 씠뿉 蹂 뿰援ъ뿉꽌뒗 理쒓렐 깉濡쒖슫 궃냼븫 醫낆뼇몴吏옄濡쒖꽌 援궡뿉꽌 엫긽쟻 궗슜씠 湲됱쬆븯怨 엳뒗 HE4 寃궗뿉 븳 쇅遺젙룄愿由щЪ吏덉쓣 젣議고븯뿬 洹 쟻빀꽦쓣 룊媛븯怨 HE4 紐⑥쓽떊鍮숇룄議곗궗瑜 떎떆븯怨좎옄 븯떎.

Figure 1.

Monthly trend of human epididymis protein 4 test usage reimbursed, based on the data from Big data Hub provided by the Health Insurance Review and Assessment Service.


Figure 2.

Monthly test volume for human epididymis protein 4 assay in a referral laboratory.


옱猷 諛 諛⑸쾿

1. 긽

2017뀈 4썡 27씪遺꽣 7썡 31씪源뚯 (옱)꽌슱쓽怨쇳븰뿰援ъ냼뿉 HE4 寃궗媛 쓽猶곕맂 솚옄瑜 긽쑝濡 HE4 寃궗 셿猷 썑 옍뿬삁泥쓣 씠슜, B삎 媛꾩뿼 몴硫댄빆썝, C삎 媛꾩뿼 빆泥 諛 human immunodeficiency virus (HIV) 빆泥닿궗瑜 떎떆븯떎. 꽭 寃궗 紐⑤몢 쓬꽦씤 옍뿬 삁泥 275媛쒕 닔吏묓븯怨 HE4 젙룄愿由щЪ吏 젣議 떆源뚯 깋룞(–20°C)븯떎. 蹂 뿰援щ뒗 (옱)꽌슱쓽怨쇳븰뿰援ъ냼 湲곌깮紐낆떖쓽쐞썝쉶濡쒕꽣 떖쓽(2017-43-01F)瑜 뱷븳 썑 吏꾪뻾릺뿀떎.

2. Human epididymis protein 4 젙룄愿由щЪ吏덉쓽 젣議

媛쒕퀎 삁泥쓽 HE4 냽룄뿉 뵲씪 삁泥쓣 꽭 援곗쑝濡 遺꾪븯뿬 –20°C뿉 깋룞 蹂닿븯怨, 깋룞삁泥쓣 떎삩뿉꽌 셿쟾엳 빐룞븳 썑 샎빀븯뿬 꽭 媛吏 떎瑜 냽룄쓽 샎二쇳삁泥쓣 젣議고븯떎. 샎二쇳삁泥뿉뒗 10% sodium azide (Sigma-Aldrich, St. Louis, MO, USA) 슜븸쓣 1% 냽룄濡 泥④븳 썑 援먮컲湲곗뿉꽌 180 rpm쓽 냽룄濡 10遺꾧컙 샎빀븯떎. 샎二쇳삁泥쓣 硫멸퇏嫄곗쫰뿉 嫄몃윭 꽟쑀냼瑜 젣嫄고븯怨, 꽭 냽룄쓽 샎二쇳삁泥쓣 媛 1.0 mL뵫 硫멸퇏맂 2.0 mL Cryogenic vial (Corning Life Science, New York, NY, USA)뿉 遺꾩<븯뿬 슌猿묒쓣 떕怨 뙆씪 븘由꾩쑝濡 遊됲븳 썑 떎떆 깋룞븯뿬(–20°C) 蹂닿븯떎.

3. 寃궗諛⑸쾿

HE4 B삎 媛꾩뿼 몴硫댄빆썝寃궗뒗 Cobas e602 (Roche Diagnostics GmbH, Mannheim, Germany)瑜 씠슜븯뿬 쟾옄솕븰諛쒓킅 硫댁뿭遺꾩꽍踰(electro-chemiluminescent immunoassay)쑝濡 寃궗븯떎. C삎 媛꾩뿼 빆泥댁 HIV 빆泥닿궗뒗 ARCHITECT i2000 (Abbott Laboratories, Abbott Park, IL, USA)쓣 씠슜븯뿬 솕븰諛쒓킅 誘몄꽭엯옄 硫댁뿭遺꾩꽍踰(chemiluminescent microparticle immunoassay)쑝濡 寃궗븯떎.

깋룞맂 HE4 샎二쇳삁泥 떎삩(20°C-25°C)뿉꽌 빐룞 썑 援먮컲湲곕 씠슜, 異⑸텇엳 샎빀븳 썑 HE4 냽룄瑜 痢≪젙븯떎. 떆빟 젣議곗궗媛 젣떆븳 HE4 寃궗쓽 젙諛룄뒗 2.6%-3.4%(룊洹좊냽룄, 27.4-1390.0 pmol/L 踰붿쐞; Cobas e602 옣鍮 湲곗)씠떎. 뿰援ъ뿉 궗슜맂 HE4 寃궗뒗 紐⑤몢 븳 떆빟 lot濡 寃궗븯怨, 빐떦 lot瑜 궗슜븯湲 쟾 옣鍮꾩쓽 蹂댁젙쓣 떆뻾븳 썑 寃궗븯떎. 留 寃궗 쟾 PreciControl HE4 (Roche Diagnostics GmbH)瑜 씠슜븯뿬 몢 냽룄쓽 궡遺젙룄愿由 寃곌낵媛 뿀슜踰붿쐞 씠궡엫쓣 솗씤븳 썑 떎뿕쓣 吏꾪뻾븯떎.

4. HHuman epididymis protein 4 젙룄愿由щЪ吏덉쓽 슜湲 媛 洹좎쭏 꽦 룊媛

遺꾩<븳 HE4 쇅遺젙룄愿由щЪ吏덉씠 슜湲 媛 洹좎쭏븳吏 솗씤븯湲 쐞븯뿬 꽭 냽룄蹂 媛 10媛쒖쓽 슜湲곕 엫쓽濡 꽑젙븳 썑 슜湲곕떦 3쉶뵫 HE4 냽룄瑜 諛섎났 痢≪젙븯떎.

5. Human epididymis protein 4 젙룄愿由щЪ吏덉쓽 븞젙꽦 룊媛

HE4 젙룄愿由щЪ吏덉쓽 蹂닿議곌굔뿉 뵲瑜 븞젙꽦쓣 룊媛븯湲 쐞븯뿬 꽭 냽룄쓽 젙룄愿由щЪ吏덉쓣 깋룞(–20°C), 깋옣(4°C) 諛 떎삩(20°C)뿉꽌 媛곴컖 24떆媛, 3씪, 7씪, 14씪, 30씪 諛 90씪 룞븞 蹂닿븯떎. 媛 蹂닿삩룄 諛 湲곌컙蹂꾨줈 슜湲곕떦 3쉶뵫 HE4 냽룄瑜 諛섎났 痢≪젙븯떎.

6. 젣議곕맂 human epididymis protein 4 젙룄愿由щЪ吏덉쓣 씠슜 븳 紐⑥쓽떊鍮숇룄議곗궗

援궡뿉꽌 HE4 寃궗瑜 떆뻾 以묒씤 湲곌뿉 씠硫붿씪쓣 諛쒖넚븯뿬 HE4 紐⑥쓽떊鍮숇룄議곗궗뿉 븳 李몄뿬 쓽뼢쓣 뙆븙븯떎. 13媛 湲곌뿉꽌 紐⑥쓽떊鍮숇룄議곗궗瑜 슂泥븯怨, 빐떦 湲곌뿉 媛 꽭 냽룄쓽 HE4 젙룄愿由щЪ吏덉쓣 諛쒖넚븯떎. 쇅遺젙룄愿由щЪ吏덉 깋룞긽깭瑜 쑀吏븯뿬 諛곗넚릺룄濡 蹂대깋옱吏덈줈 씠以묓룷옣 썑 뱶씪씠븘씠뒪瑜 6 kg뵫 뒪떚濡쒗뤌 긽옄뿉 異붽븯뿬 넻긽 깮諛곕줈 諛쒖넚븯떎. 젙룄愿由 寃곌낵쓽 쉶떊 꽌떇뿉뒗 HE4 젙룄愿由щЪ吏 닔졊 떆 깋룞긽깭 쑀吏 뿬遺瑜 湲곗엯븯룄濡 븯뿬 깋룞寃泥 닔넚諛⑸쾿뿉 븳 쟻젙꽦쓣 룊媛븯떎.

7. 넻怨꾨텇꽍

紐⑤뱺 넻怨꾨텇꽍뿉뒗 Analyse-it Software ver. 4.92.4 (Analyse-it Software Ltd., Leeds, UK)瑜 궗슜븯떎. HE4 젙룄愿由щЪ吏덉쓽 슜湲 媛 洹좎쭏룄 룊媛 떆 媛 냽룄蹂 10媛쒖쓽 슜湲곗뿉 븳 3쉶 諛섎났痢≪젙移섏쓽 珥 蹂씠怨꾩닔(total coefficient of variation [CV])瑜 怨꾩궛븯怨, 슜湲 媛 넻怨꾩쟻쑝濡 쑀쓽븳 李⑥씠媛 엳뒗吏 analysis of variance濡 룊媛븯떎. 蹂닿議곌굔뿉 뵲瑜 븞젙꽦 룊媛뿉 엳뼱 媛 냽룄蹂 HE4 湲곗移(깋룞蹂닿 썑 24떆媛 寃쎄낵븳 寃泥대 빐룞 썑 3쉶 諛섎났 痢≪젙븳 HE4 寃곌낵移) 媛 蹂닿삩룄蹂, 湲곌컙蹂 3쉶 諛섎났痢≪젙移섎 ‘Dunnett against a control comparisons’濡 遺꾩꽍븯떎. P媛믪씠 0.05 誘몃쭔씤 寃쎌슦 넻怨꾩쟻쑝濡 쑀쓽븳 寃껋쑝濡 뙋젙븯떎. 삉븳 13媛 湲곌뿉꽌 쉶떊븳 HE4 紐⑥쓽떊鍮숇룄議곗궗 寃곌낵뿉 븯뿬 떆빟蹂꾨줈 李멸湲곌쓽 룊洹, 몴以렪李 諛 媛 湲곌쓽 standard deviation index瑜 怨꾩궛븯뿬 蹂닿퀬꽌 삎깭濡 쉶떊븯떎.

寃곌낵

1. 뿰援ш린媛 룞븞쓽 human epididymis protein 4 궡遺젙룄愿 由 寃곌낵

HE4 쇅遺젙룄愿由щЪ吏덉쓽 洹좎쭏꽦 諛 븞젙꽦 떆뿕쓣 吏꾪뻾븳 90씪 룞븞 HE4 궡遺젙룄愿由 寃곌낵뒗 total CV 2.53% (mean± standard deviation [SD], 48.27±1.22 pmol/L) 諛 2.51% (341.19±8.56 pmol/L)濡 븞젙쟻씠뿀떎(Table 1).

Table 1 . Results of the internal QC testing for HE4 to assess the homogeneity and stability during the 90-day evaluation period.

QC materialsQC target mean (range) (pmol/L)6 Testing days during 90-day evaluationDuring 90-day evaluation


Mean±SD (pmol/L)CV (%)Mean±SD (pmol/L)CV (%)
PreciControl HE4 148.41 (45.32–51.5)47.89±1.302.7048.27±1.222.53
PreciControl HE4 2350.77 (328.9–372.6)348.32±6.421.84341.19±8.562.51

Abbreviations: QC, quality control; HE4, human epididymis protein 4; SD, standard deviation; CV, coefficient of variation..


2. Human epididymis protein 4 쇅遺젙룄愿由щЪ吏덉쓽 洹좎쭏꽦 룊媛 寃곌낵

HE4 쇅遺젙룄愿由щЪ吏덉쓽 슜湲 媛 洹좎쭏꽦 룊媛뿉꽌 level蹂 媛 10媛 슜湲곗뿉 븳 3쉶 諛섎났寃궗쓽 total CV뒗 떎쓬怨 媛숈븯떎: level I, 1.24% (mean HE4, 39.50 pmol/L); level II, 1.08% (mean HE4, 91.81 pmol/L); level III, 0.75% (mean HE4, 330.26 pmol/L). 꽭 level쓽 젙룄愿由щЪ吏 紐⑤몢 슜湲 媛 HE4 냽룄뿉 쑀쓽븳 李⑥씠媛 뾾뼱 洹좎쭏븳 寃껋쑝濡 룊媛븯떎(Table 2).

Table 2 . Variation in the concentrations of HE4 detected among vials in the three levels of EQA materials.

Vial no.No.Level I (pmol/L)Level II (pmol/L)Level III (pmol/L)



Mean±SDCV (%)Mean±SDCV (%)Mean±SDCV (%)
Vial 1339.68±0.411.0392.11±0.750.81327.17±1.760.54
Vial 2339.51±0.380.9791.51±0.870.95330.00±1.350.41
Vial 3339.58±0.180.4691.10±0.190.21331.67±2.510.76
Vial 4339.43±0.250.6391.62±1.451.59331.33±1.680.51
Vial 5339.35±0.090.2291.57±0.750.82331.40±4.341.31
Vial 6339.24±0.330.8392.15±1.071.17331.70±1.040.31
Vial 7339.33±0.401.0191.03±0.370.40328.73±2.940.89
Vial 8339.97±1.283.2191.86±1.241.35330.13±0.910.27
Vial 9339.41±0.250.6491.98±0.640.70330.20±2.810.85
Vial 10339.52±0.180.4593.20±0.641.40330.30±3.200.97
Total3039.50±0.451.2491.81±0.991.08330.26±2.480.75
P-value*300.82840.77230.4695

Abbreviations: HE4, human epididymis protein 4; EQA, external quality control; SD, standard deviation; CV, coefficient of variation..

*Significant results with P-values less than 0.05 (by analysis of variance).


3. Human epididymis protein 4 젙룄愿由щЪ吏덉쓽 븞젙꽦 룊媛 寃곌낵

蹂닿議곌굔뿉 뵲瑜 븞젙꽦 룊媛뿉꽌 HE4 젙룄愿由щЪ吏덉쓽 깋룞蹂닿 떆 꽭 냽룄 紐⑤몢 30씪源뚯뒗 湲곗移(깋룞 썑 24떆媛) 쑀쓽븳 李⑥씠媛 뾾뿀쑝굹, 90씪 썑뿉뒗 湲곗移섏 쑀쓽븳 李⑥씠瑜 蹂댁떎. 깋옣蹂닿 떆 24떆媛꾧퉴吏뒗 꽭 냽룄 紐⑤몢 湲곗移섏 李⑥씠媛 뾾뿀쑝굹, 깋옣 썑 3씪 썑遺꽣뒗 HE4 냽룄媛 쑀쓽븯寃 媛먯냼릺뼱 떆媛꾩씠 吏궇닔濡 洹 媛먯냼룺씠 而ㅼ죱떎. 떎삩蹂닿 떆뿉뒗 24떆媛꾩뿉룄 湲곗移섏 쑀쓽븳 李⑥씠媛 엳뿀怨, 젏李 媛먯냼 룺씠 而ㅼ졇 30씪뿉 媛옣 궙 냽룄瑜 蹂댁씠떎媛 90씪 썑뿉뒗 냽룄媛 빟媛 利앷븯떎(Table 3, Fig. 3).

Table 3 . HE4 concentration after storage under three different conditions (4°C, 20°C, and -4°C) on days 1, 3, 14, 30, and 90.

LevelStorage conditionCategoryHE4 stability test

Day 1 (n=3)Day 3 (n=3)Day 7 (n=3)Day 14 (n=3)Day 30 (n=3)Day 90 (n=3)
I-20°CMean (pmol/L)39.9139.8939.3640.6140.9938.59
P-value-1.0000.57990.38540.09550.0347
CV (%)0.870.580.140.421.022.89
4°CMean (pmol/L)39.9938.8935.7633.6427.4616.68
P-value0.9930.0079<0.0001<0.0001<0.0001<0.0001
CV (%)1.191.000.960.600.551.37
20°CMean (pmol/L)37.8432.7724.8319.3015.8418.64
P-value0.0285<0.0001<0.0001<0.0001<0.0001<0.0001
CV (%)0.630.310.240.427.169.10
II-20°CMean (pmol/L)76.2275.9074.7876.8676.9074.35
P-value-0.96630.08740.69280.64240.0230
CV (%)1.150.450.480.291.590.71
4°CMean (pmol/L)75.6673.8068.0263.9552.9232.05
P-value0.84540.0051<0.0001<0.0001<0.0001<0.0001
CV (%)1.820.570.601.100.530.77
20°CMean (pmol/L)74.2262.1346.3836.6228.9533.32
P-value0.2400<0.0001<0.0001<0.0001<0.0001<0.0001
CV (%)3.741.240.440.881.175.35
III-20°CMean (pmol/L)338.63339.27338.83344.93350.13335.17
P-value1.0000.9991.0000.24100.01210.7539
CV (%)1.530.260.590.330.711.82
4°CMean (pmol/L)337.17330.80307.13296.10250.37176.23
P-value0.93560.0063<0.0001<0.0001<0.0001<0.0001
CV (%)0.790.210.350.440.560.57
20°CMean (pmol/L)328.13288.33228.70188.43159.70172.87
P-value0.0333<0.0001<0.0001<0.0001<0.0001<0.0001
CV (%)1.290.281.292.122.673.17

Significant results with P-values less than 0.05 when compared with baseline values (1 day after freezing) are expressed in red color (derived using Dunnett’s test)..

Abbreviations: HE4, human epididymis protein 4; CV, coefficient of variation..


Figure 3.

Human epididymis protein 4 concentration after storage under three different conditions (4°C, 20°C, and -4°C) at days 1, 3, 14, 30, and 90. Level I (A), level II (B), and level III (C)


4. Human epididymis protein 4 젙룄愿由щЪ吏덉뿉 븳 紐⑥쓽떊 鍮숇룄議곗궗 寃곌낵

援궡 13媛 湲곌뿉 諛쒖넚븳 꽭 냽룄쓽 HE4 젙룄愿由щЪ吏덉 븳 湲곌留뚯쓣 젣쇅븯怨좊뒗 紐⑤몢 깋룞긽깭媛 쑀吏맂 梨 媛 湲곌뿉 諛곗넚릺뿀쓬쓣 솗씤븯떎. 젙룄愿由щЪ吏덉씠 빐룞릺뿀떎怨 떟蹂븳 븳 湲곌쓽 寃쎌슦뒗 젙룄愿由щЪ吏덉씠 썝궡 깮諛 닔졊泥섏뿉꽌 14떆媛 씠긽 諛⑹튂릺뿀뜕 삁濡, 씠썑 젙룄愿由щЪ吏덉쓣 옱諛쒖넚븯떎. HE4 떆빟(Abbott 諛 Roche) 궗슜湲곌蹂꾨줈 HE4 삁鍮꾩떊鍮숇룄議곗궗 寃곌낵瑜 굹늻뼱 遺꾩꽍븯怨(Table 4), 蹂닿퀬꽌 뼇떇뿉 遺꾩꽍寃곌낵瑜 옉꽦븯뿬 媛 湲곌뿉 쉶떊븯떎.

Table 4 . Results of the provisional external quality control for the human epididymis protein 4 assay from 13 laboratories.

LevelManu facturerNo. of laboratoriesMean±SD (pmol/L)CV (%)
IAbbott541.20±4.6711.3
Roche840.21±0.892.2
All methods1340.59±2.837.0
IIAbbott595.92±8.338.7
Roche892.84±2.332.5
All methods1394.03±5.365.7
IIIAbbott5373.08±42.8211.5
Roche8328.00±10.693.3
All methods13345.34±34.6310.0

The instruments were from the following companies: Abbott Laboratories (Abbott Park, IL, USA) and Roche Diagnostics GmbH (Mannheim, Germany)..

Abbreviations: SD, standard deviation; CV, coefficient of variation..


怨좎같

援궡 궃냼븫 솚옄쓽 5뀈 깮議댁쑉 64.1%濡, 쑀諛⑹븫(92.3%)怨 옄沅곴꼍遺븫(79.9%)뿉 鍮꾪빐 깮議댁쑉씠 뜑 궙떎. 꽭遺쟻쑝濡 蹂대㈃ 궃냼 븞뿉 援븳릺뼱 엳嫄곕굹(localized), 궃냼 洹쇱쿂 옣湲곗뿉 援븳맂(regional) 궃냼븫 5뀈 깮議댁쑉씠 媛곴컖 92.7% 諛 76.7%濡 넂吏留, 썝寃 쟾씠맂(distant) 寃쎌슦 42.3%濡 깮議댁쑉뿉 李⑥씠媛 겕誘濡 궃냼븫 議곌린吏꾨떒쓽 以묒슂꽦씠 留ㅼ슦 겕떎怨 븷 닔 엳떎[4]. Koshiyama 벑[5] 븘떆븘 뿬꽦뿉꽌 怨듦꺽쟻씤 쑀삎(type II)蹂대떎뒗 삁썑媛 뼇샇븳 쑀삎(type I)쓽 궃냼븫 鍮덈룄媛 蹂대떎 넂쑝硫, 뵲씪꽌 븘떆븘 뿬꽦뿉 엳뼱 듅엳 CA-125/吏덇꼍쑀珥덉쓬뙆珥ъ쁺닠(transvaginal sonography)怨 媛숈 궃냼븫 꽑蹂꾧궗쓽 以묒슂꽦쓣 媛뺤“븳 諛 엳떎.

삁泥 CA-125 寃궗뒗 긽뵾꽦 궃냼븫쓽 媛옣 以묒슂븳 醫낆뼇몴吏옄 以 븯굹濡, 뿬윭 븰닠떒泥댁쓽 吏移⑥뿉꽌 궃냼븫쓽 媛먮퀎吏꾨떒, 삁썑 異붿젙, 移섎즺寃쎄낵 愿李곌낵 移섎즺 썑 異붿쟻뿉 CA-125 궗슜쓣 沅뚭퀬븯怨 엳떎[6]. 븯吏留 CA-125뒗 룓寃 쟾 뿬꽦뿉꽌 깮由 떆 利앷븷 닔 엳怨, 엫떊씠굹 뼇꽦 遺씤怨 吏덊솚뿉꽌룄 利앷맆 닔 엳쑝硫, 궃냼븫씠 븘땶 떎瑜 옣湲곗쓽 醫낆뼇뿉꽌룄 긽듅쓣 蹂댁뿬 洹 듅씠룄媛 궙떎뒗 떒젏씠 엳떎[7,8]. 肉먮쭔 븘땲씪 議곌린 긽뵾꽦 궃냼븫뿉꽌뒗 CA-125 냽룄媛 寃쎈명븳 젙룄濡 利앷릺嫄곕굹 삉뒗 利앷릺吏 븡쓣 닔룄 엳뼱 議곌린븫뿉 빐꽌뒗 誘쇨컧룄媛 50%-62% 諛뽰뿉 릺吏 븡뒗떎뒗 떒젏룄 엳떎[6].

CA-125쓽 씠윭븳 떒젏쓣 蹂댁셿븯湲 쐞븯뿬 떎瑜 궃냼븫 몴吏옄뿉 븳 留롮 뿰援ш 吏꾪뻾릺뼱 솕怨, HE4媛 怨⑤컲 醫낃눼쓽 媛먮퀎吏꾨떒, 궃냼븫쓽 吏꾨떒, 移섎즺슚怨, 삁썑 뙋젙怨 옱諛 삁痢≪뿉 룄씠 릺뒗 寃껋쑝濡 蹂닿퀬릺硫댁꽌 깉濡쒖슫 궃냼븫 몴吏옄濡쒖꽌 二쇰ぉ諛쏄쾶 릺뿀떎[3]. HE4뒗 긽뵾꽦 궃냼븫뿉꽌 怨쇰컻쁽릺硫, 議곗쭅븰쟻 쑀삎 以 諛쒖깮鍮덈룄媛 媛옣 넂 옣븸꽦 궃냼븫(serous carcinoma)쓽 93%, 옄沅곷궡留됱뼇 궃냼븫(endometrioid carcinoma)쓽 100%뿉꽌 遺꾨퉬맂떎[9]. HE4뒗 듅엳 룓寃 쟾 뿬꽦뿉꽌 뼇꽦怨 븙꽦쓽 怨⑤컲 醫낃눼瑜 媛먮퀎븿뿉 엳뼱 CA-125蹂대떎 吏꾨떒쟻 듅씠룄媛 넂쑝硫[8], CA-125 HE4瑜 룞떆 痢≪젙 떆 긽뵾꽦 궃냼븫 쐞뿕援 꽑蹂꾧궗濡쒖꽌쓽 誘쇨컧룄媛 뜑 넂븘吏뒗 寃껋쑝濡 蹂닿퀬릺뼱 엳떎[10]. 삉븳 2009뀈 Moore 벑[11]씠 젣븞븳 Risk of Ovarian Malignancy Algorithm (ROMA)뒗 HE4 諛 CA-125 寃곌낵 룓寃 긽깭瑜 빀븯뿬 怨⑤컲 醫낃눼瑜 媛吏 뿬꽦쓽 궃냼븫 쐞뿕룄(risk)瑜 怨꾩궛븯룄濡 留뚮뱺 븣怨좊━利섏쑝濡, 2011뀈 誘멸뎅 FDA濡쒕꽣 뿀媛瑜 諛쏆븯怨, 援궡뿉꽌룄 理쒓렐 留롮씠 씠슜릺怨 엳떎.

理쒓렐 엫긽쟻 궗슜씠 湲됱쬆븯怨 엳뒗 HE4 寃궗뿉 븳 엫긽쟻 吏꾨떒슚쑉꽦쓣 넂씠湲 쐞빐꽌뒗 硫대븳 吏 愿由щ 넻븯뿬 HE4 냽룄瑜 젙諛븯怨 젙솗븯寃 痢≪젙븿씠 븘닔쟻씠떎. 쁽옱 CA-125뿉 븳 援궡 쇅遺젙룄愿由щ뒗 븳엫긽젙룄愿由ы삊쉶 二쇨 떊鍮숇룄議곗궗봽濡쒓렇옩뿉꽌 二쇨븯뒗 醫낆뼇몴吏옄寃궗 II뿉 룷븿릺뼱 엳쑝굹, HE4 寃궗뿉 빐꽌뒗 븘吏 援궡 쇅遺젙룄愿由ы봽濡쒓렇옩씠 留덈젴릺뼱 엳吏 븡떎. 뼢썑 HE4 寃궗뿉 븳 쇅遺젙룄愿由ы봽濡쒓렇옩쓣 룄엯븳떎硫, CA-125, HE4 븿猿 ROMA index瑜 媛숈씠 룷븿떆耳 쇅遺젙룄愿由ы봽濡쒓렇옩쓣 슫슜븯뒗 寃껋씠 蹂대떎 諛붾엺吏곹븷 寃껋쑝濡 깮媛곷맂떎.

쇅遺젙룄愿由щ 떆뻾븯湲 쐞빐꽌뒗 留롮 뼇쓽 젙룄愿由щЪ吏덉씠 븘슂븳뜲, 씠윭븳 젙룄愿由щЪ吏덉쓽 湲곗쭏슚怨쇰 理쒖냼솕븯湲 쐞븯뿬 씪諛섏씤 諛 吏꾨떒맂 븫 솚옄濡쒕꽣 웾쓽 삁븸쓣 梨꾩랬븯怨 遺꾩<븯뿬 젙룄愿由щЪ吏덉쓣 젣議고븯뒗 諛⑸쾿쓣 怨좊젮븷 닔 엳寃좊떎. 븯吏留 씠 寃쎌슦 븞쟾꽦씠굹 쑄由ъ쟻 臾몄젣 벑쑝濡 씤빐 쁽떎쟻쑝濡 뼱젮씠 뵲瑜몃떎. 뵲씪꽌 移섎즺 諛 吏꾨떒 紐⑹쟻쑝濡 쓽猶곕맂 寃궗瑜 떆뻾븳 썑 궓 옍뿬삁泥쓣 닔吏묓븯뿬 젣議고븳 젙룄愿由щЪ吏덉쓣 씠슜븯뒗 諛⑸쾿씠 씠뿉 븳 븞씠 맆 닔 엳寃좊떎. 옍뿬삁泥쓣 닔吏묓븯뿬 젣議고븳 젙룄愿由щЪ吏덉쓽 슂嫄댁쑝濡쒖꽌뒗, 媛먯뿼꽦 臾쇱쭏씠 븘떂씠 솗씤릺뼱빞 븯怨, 遺꾩꽍臾쇱쭏쓽 냽룄媛 슜湲곕쭏떎 洹좎쭏븯寃 遺꾩<릺뼱빞 븷 寃껋씠떎. 삉븳 쇅遺젙룄愿由щ 떆뻾븯湲 쐞븳 젙룄愿由щЪ吏덉 異⑸텇븳 湲곌컙 룞븞쓽 蹂닿뿉룄 븞젙쟻씠뼱빞 븯硫, 옣嫄곕━ 諛곗넚 떆뿉룄 遺꾩꽍臾쇱쭏쓽 냽룄뿉 쑀쓽븳 李⑥씠瑜 씪쑝궎吏 븡뒗 븞젙꽦씠 솗蹂대맂 諛⑸쾿쑝濡 蹂닿릺怨 諛곗넚릺뼱빞 븷 寃껋씠떎[12].

泥닿퀎쟻씤 쇅遺젙룄愿由ы봽濡쒓렇옩쓣 닔뻾븯湲 쐞빐꽌뒗 젙룄愿由щЪ吏덉쓽 醫낅쪟굹 蹂닿삩룄, 蹂닿議곌굔뿉 뵲瑜 븞젙꽦쓣 궗쟾뿉 룊媛븿씠 븘닔쟻씠떎. 젙룄愿由щЪ吏덉 룞寃곕맂(frozen) 삁泥, 븞젙솕맂 븸긽(stabilized liquid) 삁泥, 룞寃곌굔議곕맂(lyophilized) 삁泥쓽 꽭 媛吏 삎깭濡 젣議고븷 닔 엳떎. 醫낆뼇몴吏옄寃궗쓽 쇅遺젙룄愿由щЪ吏 젣議곗뿉 븳 븳 뿰援ъ뿉꽌 룞寃곌굔議곕맂 삁泥씠 룞寃곕맂 삁泥뿉 鍮꾪븯뿬 蹂닿뿉 뵲瑜 븞젙꽦씠 뼥뼱졇꽌 룞씪 蹂닿議곌굔뿉꽌 蹂닿븳 룞寃곌굔議 삁泥쓽 醫낆뼇몴吏옄 냽룄媛 룞寃곕맂 삁泥蹂대떎 궙怨 蹂씠怨꾩닔룄 겙 寃껋쑝濡 蹂닿퀬븯떎[13]. 삉븳 룞寃곌굔議 臾쇱쭏쓽 寃쎌슦 룞寃곕맂 삁泥怨쇰뒗 떖由 蹂듭썝 떆 湲곗쭏쟻 李⑥씠濡 씤븳 긽샇쟾솚꽦(commutability)쓽 臾몄젣젏뿉룄 쑀쓽빐빞 븳떎[14].

븳렪 떆빟 젣議고쉶궗쓽 꽕紐낆꽌뿉 뵲瑜대㈃ 삁泥 HE4 냽룄뒗 15°C-25°C뿉꽌 5떆媛, 2°C-8°C뿉꽌 48떆媛, –20°C뿉꽌 12二쇨퉴吏 븞젙꽦쓣 蹂댁씠뒗 寃껋쑝濡 紐낆떆릺뼱 엳떎. 蹂 뿰援ъ뿉꽌룄 HE4 샎二쇳삁泥쓣 떎삩(20°C) 蹂닿 떆 24떆媛꾨꽣 湲곗移섏뿉 鍮꾪빐 쑀쓽븳 媛먯냼瑜 蹂댁怨, 깋옣蹂닿(4°C) 떆 24떆媛꾧퉴吏 븞젙븳 寃껋쑝濡 굹궗쑝硫, 깋룞蹂닿(–20°C) 떆 30씪源뚯 븞젙븳 寃껋쓣 솗씤븷 닔 엳뿀떎. 뵲씪꽌 젣議고븳 HE4 젙룄愿由щЪ吏덉쓽 븞젙꽦 떆빟젣議고쉶궗쓽 꽕紐낆꽌뿉 븞궡맂 궡슜怨 쑀궗븳 寃껋쑝濡 룊媛릺뿀떎.

紐⑥쓽떊鍮숇룄議곗궗뿉꽌 李몄뿬湲곌 닔媛 異⑸텇移 븡븯吏留 몢 媛吏 HE4 젣뭹(Abbott 諛 Roche) 궗슜泥섎퀎濡 룊洹, SD 諛 CV瑜 援ы븯뿬 寃넗븯뒗뜲, 몢 젣뭹 궗슜湲곌 媛꾩뿉 SD CV쓽 李⑥씠瑜 蹂댁떎(Table 4). 룞 湲곌컙 蹂 寃궗떎씠 李몄뿬븯뜕 CAP HE4 survey (2017 HUEP-B) 蹂닿퀬꽌뿉꽌룄 蹂 뿰援ъ 쑀궗븯寃 몢 젣뭹 궗슜湲곌 媛꾩뿉 SD CV뿉 李⑥씠媛 엳뒗 寃껋쓣 솗씤븷 닔 엳뿀怨, 씠윭븳 李⑥씠뒗 젣뭹쓽 꽦뒫 李⑥씠뿉 湲곗씤븷 媛뒫꽦씠 엳쓣 寃껋쑝濡 깮媛곷릺뿀떎(Table 5).

Table 5 . Human epididymis protein 4 results of the participant summary in 2017 HUEP-B released by College of American Pathologists.

ManufacturerNo. of laboratoriesMean±SD (pmol/L)CV (%)
HUEP-04Abbott17293.3±24.78.4
Roche14240.1±5.92.5
All methods32270.7±33.112.2
HUEP-05Abbott17159.9±14.08.8
Roche14135.5±3.12.3
All methods32150.0±16.310.9
HUEP-06Abbott1766.8±7.010.5
Roche1461.3±1.82.9
All methods3264.0±6.19.5

The instruments were from the following companies: Abbott Labo-ratories (Abbott Park, IL, USA) and Roche Diagnostics GmbH (Mannheim, Germany)..

Abbreviations: SD, standard deviation; CV, coefficient of variation..


寃곕줎쟻쑝濡, HE4 寃궗 醫낅즺 썑 닔吏묓븳 옍뿬삁泥쓣 씠슜븯뿬 젣議고븳 꽭 냽룄쓽 HE4 젙룄愿由щЪ吏덉 슜湲곕쭏떎 洹좎쭏븯怨, 깋룞蹂닿 떆 젣議 썑 30씪源뚯 븞젙꽦씠 쑀吏릺뒗 寃껋쑝濡 룊媛릺뿀떎. 엫긽쟻쑝濡 以묒슂꽦씠 넂怨 洹 궗슜웾씠 湲됱쬆븯怨 엳뒗 HE4 媛숈 以묒슂븳 醫낆뼇몴吏옄뿉 븯뿬 援궡 쇅遺젙룄愿由ы봽濡쒓렇옩 留덈젴쓣 넻븳 吏 愿由ш 떆湲됲븯떎怨 깮媛곷맂떎.

媛먯궗쓽 湲

씠 끉臾몄 븳엫긽寃궗젙룄愿由ы삊쉶 2017뀈 븰닠뿰援щ퉬 吏썝뿉 쓽빐 씠猷⑥뼱吏 寃껋씠떎.

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