Expression of Survivin, Estrogen and Progesterone Receptor in Focal Tissues Before and After Treatment by High Intensity Focused Ultrasound for Nonneoplasia Epithelial Disorders of Skin and Mucosa of Vulva

doi:10.3877/cma.j.issn.1673-5250.2013.05.004

Objective

To investigate the expression levels and significance of estrogen receptor(ER), progesterone receptor (PR) and survivin in the focal tissues of non-neoplasia epithelial disorders of skin and mucosa of vulva(NEDV) before treatment and after 6 months of treatment by high intensity focused ultrasound(HIFU).

Methods

From January 2009 to September 2011, a total of 86 cases with NEDV, in an average age of (43.0±14.5) years old (15 to 75 years old), confirmed by biopsy pathology before treatment by HIFU, and 30 patients were randomly obtained the normal tissues nearby the focuses for control. According to histological classification of NEDV, 86 patients with NEDV were divided into three pathological types.Types of squamous hyperplasia(SHV)were 43 cases, lichen sclerosus(LSV)were 29 cases, and lichen sclerosus combined with squamous hyperplasia(LSCSH)were 14 cases.Immunohistochemical analysis for survivin, ER and PR expression were carried out on the tissue samples collected before treatment and after 6 months of treatment by HIFU. The methods of Vulvar Pruritus Score, Vulvar Leucoplakia Area Calculation and Vulvar Skin Elasticity were designed for objective evaluation of curative effect. Informed consent was obtained from all participants.

Results

After 6 months of treatment by HIFU, ① the curative rate of relieving-pruritus was 100%, and the average areas of vulvar leucoplakia of 86 patients with NEDV decreased from (11.21±7.50) cm² to (6.60±3.17) cm², and there were statistically more effective for Vulvar Pruritus Score and Vulvar Leucoplakia Area Calculation than those before treatment by HIFU(P<0.01). ②Expression levels of survivin, ER, and PR before treatment and after 6 months of treatment by HIFU, there had no statistical difference among the three pathological types: SHV, LSV and LSCSH(P>0.05), respectively. Positive rates of ER and PR expression before treatment and after 6 months of treatment by HIFU in normal vulvar tissues were much higher than those of focus tissues(P<0.05), but the survivin were much lower(P<0.05). ③Positive rates of ER and PR expression after 6 months of treatment by HIFU in focal tissues became much higher, as well as the surviving much lower than those before treatment by HIFU(P<0.05).

Conclusions

Expression levels increasing of survivin and decreasing of ER and PR could be the essential factors of pathogenesis for NEDV. Expression levels of survivin, ER and PR may play an important role in indicate the curative effect.

Key words: high intensity focused ultrasound, non-neoplasia epithelial disorders of skin and mucosa of vulva, pathogenesis, curative effect, estrogen/progesterone receptor, survivin

表1 研究组治疗前与治疗6个月时外阴瘙痒评分比较(分，±s)

Table 1 Comparison of vulvar pruritus scores before treatment and after 6 months of treatment in research group(score，±s)

组织学类型	n	评分		治愈率[n(%)]	t	P
组织学类型	n	治疗前	治疗后6个月时	治愈率[n(%)]	t	P
SHV	43	2.60±0.44	0.47±0.54	84.1(37/44)	2.857	<0.01
LSV	29	2.86±0.51	0.90±0.38	85.3(29/34)	3.184	<0.01
LSCSH	14	2.56±0.44	0.87±0.28	75.0 (6/8)	3.631	<0.01
合计	86	2.67±0.48	0.56±0.36	83.7(72/86)	2.731	<0.01

表1 研究组治疗前与治疗6个月时外阴瘙痒评分比较(分，±s)

Table 1 Comparison of vulvar pruritus scores before treatment and after 6 months of treatment in research group(score，±s)

组织学类型	n	评分		治愈率[n(%)]	t	P
组织学类型	n	治疗前	治疗后6个月时	治愈率[n(%)]	t	P
SHV	43	2.60±0.44	0.47±0.54	84.1(37/44)	2.857	<0.01
LSV	29	2.86±0.51	0.90±0.38	85.3(29/34)	3.184	<0.01
LSCSH	14	2.56±0.44	0.87±0.28	75.0 (6/8)	3.631	<0.01
合计	86	2.67±0.48	0.56±0.36	83.7(72/86)	2.731	<0.01

表2 研究组治疗前与治疗结束后6个月时外阴白色病变皮肤面积的比较(cm²，±s)

Table 2 Comparison of vulvar leucoplakia area calculation before treatment and after 6 months of treatment in research group(cm²，±s)

组织学类型	n	白色病变面积		治愈率[n(%)]	t	P
组织学类型	n	治疗前	治疗后6个月时	治愈率[n(%)]	t	P
SHV	43	12.90±6.60	3.67±1.61	77.3(34/44)	4.971	<0.01
LSV	29	10.66±3.77	4.87±1.45	58.8(20/34)	3.290	<0.01
LSCSH	14	10.99±5.34	3.87±0.28	62.5 (5/ 8)	3.321	<0.01
合计	86	11.21±7.50	6.60±3.17	68.6(59/86)	2.836	<0.01

表2 研究组治疗前与治疗结束后6个月时外阴白色病变皮肤面积的比较(cm²，±s)

Table 2 Comparison of vulvar leucoplakia area calculation before treatment and after 6 months of treatment in research group(cm²，±s)

组织学类型	n	白色病变面积		治愈率[n(%)]	t	P
组织学类型	n	治疗前	治疗后6个月时	治愈率[n(%)]	t	P
SHV	43	12.90±6.60	3.67±1.61	77.3(34/44)	4.971	<0.01
LSV	29	10.66±3.77	4.87±1.45	58.8(20/34)	3.290	<0.01
LSCSH	14	10.99±5.34	3.87±0.28	62.5 (5/ 8)	3.321	<0.01
合计	86	11.21±7.50	6.60±3.17	68.6(59/86)	2.836	<0.01

表3 研究组治疗前与治疗后6个月时外阴皮肤弹性评分比较(分，±s)

Table 3 Comparison of vulvar skin elasticity before treatment and after 6 months of treatment in research group(score，±s)

组织学类型	n	皮肤弹性评分		有效率[n(%)]	t	P
组织学类型	n	治疗前	治疗后6个月时	有效率[n(%)]	t	P
SHV	43	0.79±0.39	0.57±0.32	53.5(23/43)	1.933	>0.05
LSV	29	2.15±0.55	0.89±0.37	72.4(21/29)	3.291	<0.01
LSCSH	14	2.42±0.74	1.37±0.48	78.6(11/14)	3.291	<0.01
合计	86	2.07±0.57	0.84±0.30	64.0(55/86)	2.182	<0.05

表3 研究组治疗前与治疗后6个月时外阴皮肤弹性评分比较(分，±s)

Table 3 Comparison of vulvar skin elasticity before treatment and after 6 months of treatment in research group(score，±s)

组织学类型	n	皮肤弹性评分		有效率[n(%)]	t	P
组织学类型	n	治疗前	治疗后6个月时	有效率[n(%)]	t	P
SHV	43	0.79±0.39	0.57±0.32	53.5(23/43)	1.933	>0.05
LSV	29	2.15±0.55	0.89±0.37	72.4(21/29)	3.291	<0.01
LSCSH	14	2.42±0.74	1.37±0.48	78.6(11/14)	3.291	<0.01
合计	86	2.07±0.57	0.84±0.30	64.0(55/86)	2.182	<0.05

表4 研究组治疗前与治疗结束后6个月时3种类型外阴病变组织及其与对照组ER，PR及survivin表达水平比较 (%)

Table 4 Comparison of expression of ER, PR and survivin in focal tissues before treatment and after 6 months of treatment by HIFM among types of SHV, SHV, LSV, LSCSH in research group and in control group (%)

组别		n	ER (n)			阳性率	PR (n)			阳性率	survivin (n)			阳性率
组别		n	－	＋	≥2＋	阳性率	－	＋	≥2＋	阳性率	－	＋	≥2＋	阳性率
研究组SHV		43	?	?	?	?	?	?	?	?	?	?	?	?
?	治疗前	?	33	5	5	23.3	35	4	4	18.6	28	9	6	34.9
?	治疗后	?	23	9	11	46.5	26	8	9	39.5	40	2	1	7.0
?	χ²	?	?	?	?	5.119	?	?	?	4.586	?	?	?	10.118
?	P	?	?	?	?	0.024	?	?	?	0.033	?	?	?	0.001
研究组LSV		29	?	?	?	?	?	?	?	?	?	?	?	?
?	治疗前	?	24	2	3	17.2	25	2	2	29.4	20	5	4	31.0
?	治疗后	?	17	6	6	41.4	18	5	6	37.9	27	1	1	6.9
?	χ²	?	?	?	?	4.077	?	?	?	4.406	?	?	?	5.497
?	P	?	?	?	?	0.043	?	?	?	0.036	?	?	?	0.019
研究组LSCSH^a		14	?	?	?	?	?	?	?	?	?	?	?	?
?	治疗前	?	10	2	2	28.6	11	2	1	21.4	9	3	2	35.7
?	治疗后	?	6	4	4	57.1	7	4	3	50.0	13	1	0	7.1
?	P	?	?	?	?	0.252	?	?	?	0.236	?	?	?	0.169
研究组		86	?	?	?	?	?	?	?	?	?	?	?	?
?	治疗前	?	67	9	10	22.1	71	8	7	17.4	55	17	14	37.2
?	治疗后	?	46	19	21	46.5	41	27	18	52.3	80	4	2	7.0
?	χ²	?	?	?	?	11.377	?	?	?	23.036	?	?	?	21.522
?	P	?	?	?	?	0.001	?	?	?	0.000	?	?	?	0.000
研究组治疗前		86	67	9	10	22.1	71	8	7	17.4	55	17	14	37.2
?	对照组	30	14	7	9	53.3	19	5	6	36.7	30	0	0	0.0
?	χ²	?	?	?	?	10.303	?	?	?	4.727	?	?	?	?
?	P	?	?	?	?	0.001	?	?	?	0.03	?	?	?	?
研究组治疗后		86	46	19	21	46.5	41	27	18	52.3	80	4	2	7.0
?	对照组	30	14	7	9	53.3	19	5	6	36.7	30	0	0	0.0
?	χ²	?	?	?	?	0.414	?	?	?	2.184	?	?	?	?
?	P	?	?	?	?	0.520	?	?	?	0.924	?	?	?	?

表4 研究组治疗前与治疗结束后6个月时3种类型外阴病变组织及其与对照组ER，PR及survivin表达水平比较 (%)

组别		n	ER (n)			阳性率	PR (n)			阳性率	survivin (n)			阳性率
组别		n	－	＋	≥2＋	阳性率	－	＋	≥2＋	阳性率	－	＋	≥2＋	阳性率
研究组SHV		43	?	?	?	?	?	?	?	?	?	?	?	?
?	治疗前	?	33	5	5	23.3	35	4	4	18.6	28	9	6	34.9
?	治疗后	?	23	9	11	46.5	26	8	9	39.5	40	2	1	7.0
?	χ²	?	?	?	?	5.119	?	?	?	4.586	?	?	?	10.118
?	P	?	?	?	?	0.024	?	?	?	0.033	?	?	?	0.001
研究组LSV		29	?	?	?	?	?	?	?	?	?	?	?	?
?	治疗前	?	24	2	3	17.2	25	2	2	29.4	20	5	4	31.0
?	治疗后	?	17	6	6	41.4	18	5	6	37.9	27	1	1	6.9
?	χ²	?	?	?	?	4.077	?	?	?	4.406	?	?	?	5.497
?	P	?	?	?	?	0.043	?	?	?	0.036	?	?	?	0.019
研究组LSCSH^a		14	?	?	?	?	?	?	?	?	?	?	?	?
?	治疗前	?	10	2	2	28.6	11	2	1	21.4	9	3	2	35.7
?	治疗后	?	6	4	4	57.1	7	4	3	50.0	13	1	0	7.1
?	P	?	?	?	?	0.252	?	?	?	0.236	?	?	?	0.169
研究组		86	?	?	?	?	?	?	?	?	?	?	?	?
?	治疗前	?	67	9	10	22.1	71	8	7	17.4	55	17	14	37.2
?	治疗后	?	46	19	21	46.5	41	27	18	52.3	80	4	2	7.0
?	χ²	?	?	?	?	11.377	?	?	?	23.036	?	?	?	21.522
?	P	?	?	?	?	0.001	?	?	?	0.000	?	?	?	0.000
研究组治疗前		86	67	9	10	22.1	71	8	7	17.4	55	17	14	37.2
?	对照组	30	14	7	9	53.3	19	5	6	36.7	30	0	0	0.0
?	χ²	?	?	?	?	10.303	?	?	?	4.727	?	?	?	?
?	P	?	?	?	?	0.001	?	?	?	0.03	?	?	?	?
研究组治疗后		86	46	19	21	46.5	41	27	18	52.3	80	4	2	7.0
?	对照组	30	14	7	9	53.3	19	5	6	36.7	30	0	0	0.0
?	χ²	?	?	?	?	0.414	?	?	?	2.184	?	?	?	?
?	P	?	?	?	?	0.520	?	?	?	0.924	?	?	?	?

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