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

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

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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