免疫细胞化学检测微小染色体维持蛋白2在宫颈病变诊断中的价值及其与人乳头瘤病毒感染的关系

doi:10.3877/cma.j.issn.1673-5250.2013.06.006

中华妇幼临床医学杂志(电子版) ›› 2013, Vol. 09 ›› Issue (06) : 744 -749. doi: 10.3877/cma.j.issn.1673-5250.2013.06.006

所属专题：文献；

论著

免疫细胞化学检测微小染色体维持蛋白2在宫颈病变诊断中的价值及其与人乳头瘤病毒感染的关系

郑健¹^,^*^,^*(

), 任杰¹, 幺磊¹, 宋静慧¹

^1. 010059　内蒙古自治区呼和浩特，内蒙古医科大学附属医院妇产科

收稿日期:2013-05-24 修回日期:2013-11-12 出版日期:2013-12-01
通信作者: 郑健

Diagnosis Value of Minichromosome Maintenance Protein 2 by Immunocytochemical Test on Cervical Lesions and Its Relationship With Human Papillomavirus Infection

Jian ZHENG¹(), Jie REN¹, Lei YAO¹, Jing-hui SONG¹

^1. Department of Gynecology and Obstetrics, Affiliated Hospital of Inner Mongolia Medical University , Huhhot 010059, Inner Mongolia, China

Received:2013-05-24 Revised:2013-11-12 Published:2013-12-01
Corresponding author: Jian ZHENG
About author:
(Corresponding author : ZHENG Jian , Email : zhengjian625@126. com)

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引用本文：

郑健, 任杰, 幺磊, 宋静慧. 免疫细胞化学检测微小染色体维持蛋白2在宫颈病变诊断中的价值及其与人乳头瘤病毒感染的关系[J]. 中华妇幼临床医学杂志(电子版), 2013, 09(06): 744-749.

Jian ZHENG, Jie REN, Lei YAO, Jing-hui SONG. Diagnosis Value of Minichromosome Maintenance Protein 2 by Immunocytochemical Test on Cervical Lesions and Its Relationship With Human Papillomavirus Infection[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2013, 09(06): 744-749.

目的

探讨微小染色体维持蛋白2(MCM2)在宫颈病变中的表达和临床意义及其与人乳头瘤病毒(HPV)感染的关系。

方法

选取2011年10月到2012年12月在内蒙古医科大学附属医院妇产科就诊并行宫颈薄层液基细胞学检查(TCT)检查和13种高危型HPV(HR-HPV)分型检测的183例宫颈病变患者为研究对象，并对TCT剩余标本进行MCM2免疫细胞化学染色，并与宫颈组织的病理学检查结果进行比较（本研究遵循的程序符合内蒙古医科大学附属医院人体试验委员会制定的伦理学标准，得到该委员会批准，并征得受试对象的知情同意）。

结果

MCM2的阳性表达率和HR-HPV阳性率随宫颈病变的加重而升高。MCM2与HR-HPV间的表达，具有显著意义的一致性（χ²=15.28，P<0.05）。183例患者中，MCM2和HR-HPV及二者联合筛查CIN Ⅱ及以上病变的灵敏度分别为93.81%，88. 66%和97.94%，特异性分别为88.00%，77. 55%和91.67%。而在83例ASCUS中，MCM2和HR-HPV及二者联合筛查CIN I及以上病变的灵敏度分别为72.09%，62. 79%和86. 05%，特异性分别为67. 57%，55.56 %和66. 67%,对筛查CIN Ⅱ及以上病变的灵敏度分别为86.36%，68. 18%和90. 90%，特异性分别为91.89%，80. 56%和88.89%。

结论

MCM2在宫颈癌和癌前病变中高表达，与HR-HPV的表达相一致。MCM2免疫细胞化学检测优于HR-HPV检测，可作为ASCUS管理和宫颈癌及癌前病变筛查的辅助性标志物，二者联合应用能提高诊断的灵敏度和特异性，但在ASCUS管理上MCM2免疫细胞化学检测的特异性更高。

关键词: 微小染色体维持蛋白2, 人乳头瘤病毒, 细胞学技术, 宫颈肿瘤

Objective

To explore the expression and clinical significance of minichromosome maintenance protein 2 (MCM2) in cervical lesions and its relationship with human papillomavirus (HPV) infection.

Methods

From October 2011 to December 2012,a total of 183 cases of cervical lesions suffered from Thinprep liquid-based cytology test (TCT) and the expressions of 13 kinds of high-risk HPV (HR-HPV) types were detected. Meanwhile, MCM2 immunocytochemical test was performed on liquid-based pap smears from the 183 remained TCT samples. Those results were compared with the cervical histopathology results. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Affiliated Hospital of Inner Mongolia Medical University. Informed consent was obtained from all participates.

Results

The positive expression rate of MCM2 and HR-HPV were raised accompanying with the severity of cervical lesions. MCM2 expression with HR-HPV had significant consistency (P<0. 05). In 183 cases, the sensitivity of MCM2,HR- HPV types and the combination for detecting the CIN Ⅱ or worse were 93. 81%,88. 66% and 97. 94%,the specificity were 88. 0%,77. 55% and 91. 67%, respectively. While in 83 ASCUS cases, the sensitivity of MCM2, HR- HPV and the combination for detecting the CIN I or worse were 72. 09%,62. 79 % and 86. 05%,the specificity were 67. 57 % , 55. 56 % and 66. 67%,respectively. Whereas the sensitivity of them for detecting the CIN Ⅱ or worse were 86. 36%, 68. 18% and 90. 90%, the specificity were 91. 89%, 80. 56% and 88. 89%, respectively.

Conclusions

In cervical carcinoma and precancerous lesions,MCM2 is overexpressed and consistent with the HR-HPV expression. As MCM2 immunocytochemical detection is better than HR-HPV detection, MCM2 may serve as a useful marker in the screening of cervical carcinoma and precancerous lesions and help in further upgrading the diagnosis of ASCUS. The joint application can improve the sensitivity and specificity of diagnosis,but in ASCUS management MCM2 immunocytochemical detection has higher specificity.

Key words: minichromosome maintenance protein 2, human papillomavirus, cytological techniques, uterine cervical neoplasm

图1 MCM2蛋白在不同病变宫颈脱落细胞中免疫细胞化学染色情况(SP × 200).阳性着色位于细胞核中

Figure 1 MCM2 protein immunocytochemical staining in different cervical lession cells (SP × 200). positive staining in the nucleus

表1 MCM2蛋白和HR-HPV在不同细胞学和组织学诊断中的表达(％)

Table 1 Expression of MCM2 protein and HR-HPV in different diagnosis of cytology and histology (%)

病变类别		n	MCM2的表达(n)					HR-HPV的表达(n)
病变类别		n	-	+	+ +	+ + +	阳性率	-	+	阳性率
细胞学诊断		?	?	?	?	?	?	?	?	?
?	SCC	9	0	1	1	7	100.00^a	0	9	100. 00^a'
?	HSIL	39	2	6	6	25	94. 87^b	4	35	89. 74^b'
?	LSIL	45	6	12	9	18	86. 67^c	2	43	95. 56^c'
?	ASCUS	83	37	29	9	8	55. 42^d	36	47	56. 63^d'
?	NILM	7	5	2	0	0	28. 57^e	7	0	0. 00^e'
组织学诊断		?	?	?	?	?	?	?	?	?
?	SCC	37	1	3	4	29	97. 30^f	4	33	89. 19^f'
?	CIN Ⅲ	38	1	9	11	17	97. 37^g	1	37	97. 37^g'
?	CIN Ⅱ	22	4	6	7	5	81.82^h	6	16	72. 73^h'
?	CIN I	29	12	15	0	2	58. 62ⁱ	9	20	68. 97ⁱ'
?	慢性炎症	57	32	17	3	5	43. 86^j	29	28	49.12^j'

表1 MCM2蛋白和HR-HPV在不同细胞学和组织学诊断中的表达(％)

Table 1 Expression of MCM2 protein and HR-HPV in different diagnosis of cytology and histology (%)

病变类别		n	MCM2的表达(n)					HR-HPV的表达(n)
病变类别		n	-	+	+ +	+ + +	阳性率	-	+	阳性率
细胞学诊断		?	?	?	?	?	?	?	?	?
?	SCC	9	0	1	1	7	100.00^a	0	9	100. 00^a'
?	HSIL	39	2	6	6	25	94. 87^b	4	35	89. 74^b'
?	LSIL	45	6	12	9	18	86. 67^c	2	43	95. 56^c'
?	ASCUS	83	37	29	9	8	55. 42^d	36	47	56. 63^d'
?	NILM	7	5	2	0	0	28. 57^e	7	0	0. 00^e'
组织学诊断		?	?	?	?	?	?	?	?	?
?	SCC	37	1	3	4	29	97. 30^f	4	33	89. 19^f'
?	CIN Ⅲ	38	1	9	11	17	97. 37^g	1	37	97. 37^g'
?	CIN Ⅱ	22	4	6	7	5	81.82^h	6	16	72. 73^h'
?	CIN I	29	12	15	0	2	58. 62ⁱ	9	20	68. 97ⁱ'
?	慢性炎症	57	32	17	3	5	43. 86^j	29	28	49.12^j'

表2 MCM2与HR-HPV的关系[n(%)]

Table 2 Relationship between MCM2 and HR-HPV [n(%)]

HR-HPV感染	n	MCM2的表达
HR-HPV感染	n	-	+	+ +	+ + +
呈阳性	134	26(19. 40)	35(26.12)	23(17. 16)	50(37. 31)
呈阴性	49	24(48. 98)	15(30. 61)	2(4. 08)	8(16. 33)
合计	183	50(27. 32)	50(27. 32)	25(13. 66)	58(31. 69)

表2 MCM2与HR-HPV的关系[n(%)]

Table 2 Relationship between MCM2 and HR-HPV [n(%)]

HR-HPV感染	n	MCM2的表达
HR-HPV感染	n	-	+	+ +	+ + +
呈阳性	134	26(19. 40)	35(26.12)	23(17. 16)	50(37. 31)
呈阴性	49	24(48. 98)	15(30. 61)	2(4. 08)	8(16. 33)
合计	183	50(27. 32)	50(27. 32)	25(13. 66)	58(31. 69)

表3 CINE及以上病变筛查的比较[n(%)]

Table 3 Comparison of CIN 2 or worse lesion screening[n(%)]

病变分类	n	MCM2的表达		高危型HPV的表达		MCM2 +高危型HPV的表达
病变分类	n	+	-	+	-	+	-
CIN Ⅱ及以上病变	97	91(93.81)^a	6 (6. 19)	86(88.66)^b	11 (11. 34)	95(97.94)^c	2 (2.06)
CIN I及慢性炎症	86	42(48.84)	44(51. 16)	48(55. 81)	38(44. 19)	64(74. 42)	22(25. 58)
合计	183	133(72.68)	50(27. 32)	134(73. 22)	49(26. 78)	159(86. 89)	24(13. 11)

表3 CINE及以上病变筛查的比较[n(%)]

Table 3 Comparison of CIN 2 or worse lesion screening[n(%)]

病变分类	n	MCM2的表达		高危型HPV的表达		MCM2 +高危型HPV的表达
病变分类	n	+	-	+	-	+	-
CIN Ⅱ及以上病变	97	91(93.81)^a	6 (6. 19)	86(88.66)^b	11 (11. 34)	95(97.94)^c	2 (2.06)
CIN I及慢性炎症	86	42(48.84)	44(51. 16)	48(55. 81)	38(44. 19)	64(74. 42)	22(25. 58)
合计	183	133(72.68)	50(27. 32)	134(73. 22)	49(26. 78)	159(86. 89)	24(13. 11)

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