早期蕈样肉芽肿紫外线光疗疗前疗后临床、病理和分子生物学变化的研究
发布时间：2018-07-29 20:41
【摘要】：目的：通过对24例皮肤T细胞淋巴瘤(cutaneous T-cell lymphoma, CTCL)中最常见的蕈样肉芽肿(mycosis fungoides, MF)早期(I A, IB,ⅡA期)患者经PUVA和NB-UVB等治疗前后临床分析，同时与国内外的文献进行对比分析，进一步探讨光疗对蕈样肉芽肿的有效性和安全性分析。 材料和方法：收集2003年9月至2010年7月期间北京协和医院皮肤科诊治的24例经病理检查证实的MF患者。标本均为10%福尔马林固定，常规脱水、石蜡包埋切片、HE染色、SP法免疫组化染色，PUVA采用waldmann(7001K), NB-UVB采用waldmann(7001)。 回顾性分析患者性别、发病年龄、TNM分期、治疗方法、治疗时间、治疗次数、维持治疗时间、基因重排、预后及复发等。应用SPSS17.0统计软件进行数据分析，P0.05有统计学意义。 结果：男性13例(13/24,54.2%)，女性11例(11/24,45.8%)，男女比例1.18:1。所有病例标本均根据临床皮损面积和病理表现并结合免疫组化确诊分级，按照TNM分期标准，T1N0M0期6例(25%)，TINxMO期1例(4.2%),T2N0M0期15例(62.5%)，T2N1M0期1例(4.2%)，其中ⅠA期6例(25%)，ⅠB期15例(62.5%),ⅡA期3例(12.5%)。平均发病年龄33.67岁[26.2647～41.0686]，平均治疗次数104.5次[75.71～133.29]，平均治疗时12.875月[9.90～15.85]，平均维持治疗时间11.08月[2.13～20.04]。其中完全治愈13例(54.2%)，部分治愈8例(33.3%)，缓解3例(12.5%)，无改善0例，恶化0例(0%)，复发8例(33.3%)，使用放射治疗3例(12.5%),基因重排(TCR)检查共6例，其中阳性2例(33.3%),阴性4例(66.7%)。仅采用PUVA治疗9例(37.5%)，仅NB-UVB治疗6例(25%)，PUVA治疗有效后采用联合NB-UVB合用9例(37.5%)。PUVA治疗的患者中(n=9)，治疗有效率(完全缓解＋部分缓解)为88.89%，复发率为11.11%;NB-UVB治疗组中(n=6)，治疗有效率为100%,复发率为33.33%；联合治疗组中(n=9)有效率为77.78%复发率为55.56%。三种治疗方法之间治疗次数、治疗时间、维持治疗时间、有效率和复发率无显著性差异(治疗次数P值=0.132，治疗时间P值，，0.675，维持治疗时间P值=0.347,有效率P值=0.473，复发率P值=0.147，显著性差异P0.05) 结论：PUVA和NB-UVB是治疗早期MF有效的皮肤靶向治疗方法。NB-UVB适合皮损浸润较浅,病情早期的患者,PUVA更适合皮损浸润较深,病情较重的患者,而PUVA治疗缓解后,再用NB-UVB维持治疗的方法可减少UVA的总摄入量,减少了潜在的致癌风险。 目的：紫外线光疗治疗早期MF安全有效,但其治疗前后病理改变目前研究较少。通过对24例早期MF患者经PUVA和NB-UVB以及联合治疗前后病理表现的分析,同时与国内外的文献进行对比分析,进一步探讨早期MF的病理诊断标准、光疗前后病理变化,为早期诊断MF以及光疗治疗早期MF提供病理上的支持。材料和方法：收集2003年9月至2010年7月期间北京协和医院皮肤科诊治的24例经病理检查证实的MF患者光疗前后的48分皮肤病理标本。标本均为10%福尔马林固定,常规脱水、石蜡包埋切片、HE染色。 分析和总结24例早期MF患者在光疗前后病理上变化,包括亲表皮性、角质层变化、表皮变化、炎症浸润模式、血管扩张、真皮纤维化、以及其他真皮变化等方面进行总结。应用SPSS17.0统计软件进行数据分析,P0.05有统计学意义。结果：治疗前后,24例患者48份病理标本其表现在淋巴细胞于表皮Paget样分布(P0.05)、Pautrier微脓疡(P0.01)、真皮苔藓样浸润(P0.05)、纤维化(P0.01)及血管扩张(P0.01)等方面上有显著性差异。 结论：光疗是治疗早期MF有效的治疗方法。光疗可以改变MF亲表皮性、真皮浸润模式、纤维化程度以及血管扩张,在病理学上,判断治疗是否有效以及描述光疗治疗早期MF病理变化时应注意亲表皮性、真皮浸润模式、纤维化程度以及血管扩张的改变。 目的：通过对光疗前后24例早期MF患者皮损中BCL-2、STAT-3、CCL17、CCL27表达变化的研究,进一步检测光疗前后MF肿瘤细胞的抗凋亡能力,以及表皮趋化因子表达的变化,研究光疗治疗早期MF可能的作用机制。 材料和方法：收集2003年9月至2010年7月期间北京协和医院皮肤科诊治的24例经病理检查证实的早期MF患者经光疗治疗前后的共48例皮损标本。经免疫组化染色方法检测皮损中BCL-2、STAT-3、CCL17、CCL27表达情况,以正常人眼皮组织作为阴性对照,光镜下计数阳性细胞结果。 应用SPSS17.0统计软件进行数据分析,免疫组化结果应用Pearson卡方检验,P0.05为差异有统计学意义。 结果：经紫外线治疗后,早期MF患者皮损中BCL-2表达较治疗前下降,有显著性差异(X2=13.195,P0.05)；表皮中CCL17和CCL27表达下降,有显著性差异(前者X2=8.703,P0.05；后者X2=10.783, P0.05); STAT3在淋巴细胞中表达阳性率下降,但无统计学差异(X2=2.421,P0.05)；在表皮中表达下降,有显著性差异(X2=8.171,P0.05)。 结论：紫外线光疗疗法可能通过以下机制对早期MF起治疗作用：下调BCL-2的表达,而促进皮损内肿瘤细胞的凋亡；并通过下调表皮内趋化因子的表达,抑制淋巴细胞向表皮内浸润；通过抑制细胞信号转录和活化,促进肿瘤细胞的凋亡。应用紫外线光疗疗法对早期MF进行姑息疗法是有效的治疗方法。 目的：采用实时荧光定量PCR方法检测早期MF经紫外线光疗前后患者BCL-2/IgH融合基因拷贝数的变化及其与复发和疗效的关系,探讨紫外线光疗可能的作用机制。 材料和方法：提取本研究中入组的24例早期MF患者经紫外线光疗治疗前后的石蜡包埋组织中DNA,以预实验中阳性表达者为阳性对照,蒸馏水为空白对照,正常人为阴性对照,经实时荧光定量PCR方法检测治疗前后BCL-2/IgH拷贝数量的变化,并与复发和疗效进行统计学分析,探讨紫外线光疗治疗早期MF疗效和疾病转归的关系和光疗可能的作用机制。 结果：早期MF患者在治疗前后皮损组织中BCL-2/IgH融合基因的相对表达值(△CT)P0.05,差异无统计学意义；治疗前后BCL-2/IgH上调或下调与复发及疗效之间相关性无统计学意义。 结论：紫外线光疗治疗早期MF可以下调BCL-2蛋白表达可能具有其他的非特异性途径,而不是通过减少BCL-2/IgH融合基因的拷贝数调节。
[Abstract]:Objective: to further explore the effectiveness of phototherapy on mycosis fungoides by comparing and analyzing the clinical analysis of the most common cutaneous fungoides (MF) patients (I A, IB, A phase) in 24 cases of cutaneous T-cell lymphoma (CTCL) (I A, IB, MF). Analysis of sex and safety.
Materials and methods: 24 MF patients in the Department of Dermatology of Peking Union Medical College Hospital from September 2003 to July 2010 were collected and confirmed by pathological examination. All the specimens were 10% formalin fixed, routine dehydration, paraffin embedded section, HE staining, SP immunohistochemical staining, Waldmann (7001K), NB-UVB with Waldmann (7001).
Retrospective analysis of patients' sex, age of onset, TNM stage, treatment method, time of treatment, times of treatment, maintenance time, gene rearrangement, prognosis and recurrence, and so on. The application of SPSS17.0 statistics software for data analysis, P0.05 has statistical significance.
Results: 13 male cases (13/24,54.2%) and 11 women (11/24,45.8%). All cases of male and female 1.18:1. cases were classified according to clinical skin lesion area and pathological manifestation combined with immunohistochemistry. According to the standard of TNM staging, 6 cases (25%) in T1N0M0 stage, 1 cases (4.2%) in TINxMO stage, 15 in T2N0M0 phase (62.5%), 1 in T2N1M0 phase (4.2%), of which 6 cases of stage I A (25%), There were 15 cases (62.5%) in phase I B and 3 cases (12.5%) in phase II A. The average age of onset was 33.67 years [26.2647 to 41.0686], and the average number of times of treatment was 104.5 [75.71 to 133.29]. The average treatment was 12.875 months [9.90 to 15.85], and the average maintenance time was 11.08 months [2.13 ~ 20.04]., of which 13 cases (54.2%) were completely cured and 8 cases (33.3%) were cured partly, and 3 cases (12.5%) were relieved and no improvements were made. There were 0 cases (0%), 8 cases (33.3%), 3 cases (12.5%) and 6 cases of gene rearrangement (TCR), of which 2 were positive (33.3%), and 4 (66.7%) were negative. Only 8 cases (37.5%) were treated with PUVA only, and only NB-UVB was used in 8 cases. The effective treatment was effective (n=9). Total remission + partial remission) was 88.89%, the recurrence rate was 11.11%, NB-UVB treatment group (n=6), the effective rate of treatment was 100%, the recurrence rate was 33.33%; the rate of 77.78% recurrence rate of the combined treatment group (n=9) was the number of treatment times, the time of treatment, the time of maintenance, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the rate of treatment and the recurrence rate, there was no significant difference between the treatment group and the recurrence rate. Times P value =0.132, treatment time P value, 0.675, maintenance treatment time P value =0.347, effective P value =0.473, recurrence rate P value =0.147, significant difference P0.05)
Conclusion: PUVA and NB-UVB are effective skin targeting therapy for early MF..NB-UVB is suitable for skin lesions with shallow lesions. In early patients, PUVA is more suitable for patients with deeper and heavier lesions. After PUVA treatment, NB-UVB maintenance therapy can reduce the total intake of UVA and reduce the potential carcinogenic risk.
Objective: ultraviolet phototherapy for early MF is safe and effective, but the pathological changes of the early MF patients are seldom studied. Through the analysis of the pathological manifestations of 24 early MF patients before and after PUVA and combined treatment, and compared with the literature at home and abroad, the pathological diagnostic criteria of early MF, pathology before and after phototherapy are further explored. Change, provide pathological support for early diagnosis of MF and early phototherapy MF. Materials and methods: collect 48 skin pathological specimens of 24 cases of MF patients before and after phototherapy confirmed by pathology in the Department of Dermatology, Peking Union Medical College Hospital from September 2003 to July 2010. All specimens were 10% formalin fixation, routine dehydration, paraffin paraffin Buried slices, HE staining.
Analysis and summary of 24 cases of early MF patients before and after phototherapy pathological changes, including pro epidermis, cuticle changes, epidermal changes, inflammatory infiltration patterns, vascular dilatation, dermis fibrosis, and other dermal changes are summarized. The application of SPSS17.0 statistical software for data analysis, P0.05 has statistical significance. Results: before and after treatment, 2 48 pathological specimens of 4 patients showed significant differences in lymphocytes from epidermal Paget like distribution (P0.05), Pautrier microabscess (P0.01), dermal moss like infiltration (P0.05), fibrosis (P0.01) and vasodilatation (P0.01).
Conclusion: phototherapy is an effective treatment for early MF. Phototherapy can change the epidermis of MF, the mode of dermal infiltration, the degree of fibrosis, and vasodilatation. In pathology, it is necessary to judge whether the treatment is effective and to describe the pathological changes of MF in the early stage of phototherapy, and should pay attention to the epidermis, the model of dermal infiltration, the degree of fibrosis and the vasodilation. Chang's change.
Objective: to further detect the anti apoptosis ability of MF tumor cells before and after phototherapy and the changes of the expression of epidermal chemotactic factor before and after phototherapy, and to study the possible mechanism of early phototherapy for the treatment of MF in 24 cases of early MF patients' skin lesions before and after phototherapy.
Materials and methods: 24 cases of early MF patients in the Department of Dermatology, Peking Union Medical College Hospital, from September 2003 to July 2010, were treated with pathological examination, and 48 cases of skin lesions were collected before and after phototherapy. The BCL-2, STAT-3, CCL17, CCL27 in the skin lesions were detected by immunohistochemical staining, and the normal human eyelid tissue was used as negative. The results of positive cells were counted under light microscope.
SPSS17.0 statistical software was used for data analysis. Immunohistochemical results were analyzed by Pearson chi square test, and P0.05 was statistically significant.
Results: after the treatment of ultraviolet radiation, the expression of BCL-2 in the skin lesions of early MF patients decreased significantly (X2=13.195, P0.05), and the expression of CCL17 and CCL27 in the epidermis decreased significantly (the former X2=8.703, P0.05; the latter X2=10.783, P0.05), and STAT3 in the lymphocyte, but there was no statistical difference (X2=2.421) (P0.05), there was significant difference in the epidermis (X2=8.171, P0.05).
Conclusion: UV phototherapy may play a therapeutic role in early MF by lowering the expression of BCL-2 and promoting the apoptosis of tumor cells in skin lesions, and inhibiting the infiltration of lymphocytes into the epidermis by lowering the expression of chemokines in the epidermis, and promoting the apoptosis of tumor cells by inhibiting cell signal transcription and activation. The application of ultraviolet phototherapy to palliative treatment of early MF is an effective treatment.
Objective: to detect the changes in the copy number of the BCL-2/IgH fusion gene of the early MF patients before and after ultraviolet phototherapy, and to explore the possible mechanism of the possible action of UV phototherapy by real time fluorescence quantitative PCR.
Materials and methods: 24 early MF patients in this study were extracted from the paraffin embedded tissues of DNA before and after ultraviolet phototherapy. The positive controls were positive in the pre experiment, the distilled water was the blank control and the normal human negative control. The changes of the number of BCL-2/IgH copies before and after the treatment were detected by real time fluorescence quantitative PCR method. And the recurrence and curative effect were statistically analyzed to explore the relationship between the efficacy of ultraviolet phototherapy and the prognosis of early MF, and the possible mechanism of phototherapy.
Results: the relative expression of BCL-2/IgH fusion gene (delta CT) P0.05 in the skin lesions of early MF patients was not statistically significant. There was no statistically significant correlation between the up-regulation and down regulation of BCL-2/IgH before and after treatment.
Conclusion: the early MF can reduce the expression of BCL-2 protein with other non specific pathways, not by reducing the copy number of the BCL-2/IgH fusion gene.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R739.5
本文编号：2153954
[Abstract]:Objective: to further explore the effectiveness of phototherapy on mycosis fungoides by comparing and analyzing the clinical analysis of the most common cutaneous fungoides (MF) patients (I A, IB, A phase) in 24 cases of cutaneous T-cell lymphoma (CTCL) (I A, IB, MF). Analysis of sex and safety.
Materials and methods: 24 MF patients in the Department of Dermatology of Peking Union Medical College Hospital from September 2003 to July 2010 were collected and confirmed by pathological examination. All the specimens were 10% formalin fixed, routine dehydration, paraffin embedded section, HE staining, SP immunohistochemical staining, Waldmann (7001K), NB-UVB with Waldmann (7001).
Retrospective analysis of patients' sex, age of onset, TNM stage, treatment method, time of treatment, times of treatment, maintenance time, gene rearrangement, prognosis and recurrence, and so on. The application of SPSS17.0 statistics software for data analysis, P0.05 has statistical significance.
Results: 13 male cases (13/24,54.2%) and 11 women (11/24,45.8%). All cases of male and female 1.18:1. cases were classified according to clinical skin lesion area and pathological manifestation combined with immunohistochemistry. According to the standard of TNM staging, 6 cases (25%) in T1N0M0 stage, 1 cases (4.2%) in TINxMO stage, 15 in T2N0M0 phase (62.5%), 1 in T2N1M0 phase (4.2%), of which 6 cases of stage I A (25%), There were 15 cases (62.5%) in phase I B and 3 cases (12.5%) in phase II A. The average age of onset was 33.67 years [26.2647 to 41.0686], and the average number of times of treatment was 104.5 [75.71 to 133.29]. The average treatment was 12.875 months [9.90 to 15.85], and the average maintenance time was 11.08 months [2.13 ~ 20.04]., of which 13 cases (54.2%) were completely cured and 8 cases (33.3%) were cured partly, and 3 cases (12.5%) were relieved and no improvements were made. There were 0 cases (0%), 8 cases (33.3%), 3 cases (12.5%) and 6 cases of gene rearrangement (TCR), of which 2 were positive (33.3%), and 4 (66.7%) were negative. Only 8 cases (37.5%) were treated with PUVA only, and only NB-UVB was used in 8 cases. The effective treatment was effective (n=9). Total remission + partial remission) was 88.89%, the recurrence rate was 11.11%, NB-UVB treatment group (n=6), the effective rate of treatment was 100%, the recurrence rate was 33.33%; the rate of 77.78% recurrence rate of the combined treatment group (n=9) was the number of treatment times, the time of treatment, the time of maintenance, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the treatment time, the rate of treatment and the recurrence rate, there was no significant difference between the treatment group and the recurrence rate. Times P value =0.132, treatment time P value, 0.675, maintenance treatment time P value =0.347, effective P value =0.473, recurrence rate P value =0.147, significant difference P0.05)
Conclusion: PUVA and NB-UVB are effective skin targeting therapy for early MF..NB-UVB is suitable for skin lesions with shallow lesions. In early patients, PUVA is more suitable for patients with deeper and heavier lesions. After PUVA treatment, NB-UVB maintenance therapy can reduce the total intake of UVA and reduce the potential carcinogenic risk.
Objective: ultraviolet phototherapy for early MF is safe and effective, but the pathological changes of the early MF patients are seldom studied. Through the analysis of the pathological manifestations of 24 early MF patients before and after PUVA and combined treatment, and compared with the literature at home and abroad, the pathological diagnostic criteria of early MF, pathology before and after phototherapy are further explored. Change, provide pathological support for early diagnosis of MF and early phototherapy MF. Materials and methods: collect 48 skin pathological specimens of 24 cases of MF patients before and after phototherapy confirmed by pathology in the Department of Dermatology, Peking Union Medical College Hospital from September 2003 to July 2010. All specimens were 10% formalin fixation, routine dehydration, paraffin paraffin Buried slices, HE staining.
Analysis and summary of 24 cases of early MF patients before and after phototherapy pathological changes, including pro epidermis, cuticle changes, epidermal changes, inflammatory infiltration patterns, vascular dilatation, dermis fibrosis, and other dermal changes are summarized. The application of SPSS17.0 statistical software for data analysis, P0.05 has statistical significance. Results: before and after treatment, 2 48 pathological specimens of 4 patients showed significant differences in lymphocytes from epidermal Paget like distribution (P0.05), Pautrier microabscess (P0.01), dermal moss like infiltration (P0.05), fibrosis (P0.01) and vasodilatation (P0.01).
Conclusion: phototherapy is an effective treatment for early MF. Phototherapy can change the epidermis of MF, the mode of dermal infiltration, the degree of fibrosis, and vasodilatation. In pathology, it is necessary to judge whether the treatment is effective and to describe the pathological changes of MF in the early stage of phototherapy, and should pay attention to the epidermis, the model of dermal infiltration, the degree of fibrosis and the vasodilation. Chang's change.
Objective: to further detect the anti apoptosis ability of MF tumor cells before and after phototherapy and the changes of the expression of epidermal chemotactic factor before and after phototherapy, and to study the possible mechanism of early phototherapy for the treatment of MF in 24 cases of early MF patients' skin lesions before and after phototherapy.
Materials and methods: 24 cases of early MF patients in the Department of Dermatology, Peking Union Medical College Hospital, from September 2003 to July 2010, were treated with pathological examination, and 48 cases of skin lesions were collected before and after phototherapy. The BCL-2, STAT-3, CCL17, CCL27 in the skin lesions were detected by immunohistochemical staining, and the normal human eyelid tissue was used as negative. The results of positive cells were counted under light microscope.
SPSS17.0 statistical software was used for data analysis. Immunohistochemical results were analyzed by Pearson chi square test, and P0.05 was statistically significant.
Results: after the treatment of ultraviolet radiation, the expression of BCL-2 in the skin lesions of early MF patients decreased significantly (X2=13.195, P0.05), and the expression of CCL17 and CCL27 in the epidermis decreased significantly (the former X2=8.703, P0.05; the latter X2=10.783, P0.05), and STAT3 in the lymphocyte, but there was no statistical difference (X2=2.421) (P0.05), there was significant difference in the epidermis (X2=8.171, P0.05).
Conclusion: UV phototherapy may play a therapeutic role in early MF by lowering the expression of BCL-2 and promoting the apoptosis of tumor cells in skin lesions, and inhibiting the infiltration of lymphocytes into the epidermis by lowering the expression of chemokines in the epidermis, and promoting the apoptosis of tumor cells by inhibiting cell signal transcription and activation. The application of ultraviolet phototherapy to palliative treatment of early MF is an effective treatment.
Objective: to detect the changes in the copy number of the BCL-2/IgH fusion gene of the early MF patients before and after ultraviolet phototherapy, and to explore the possible mechanism of the possible action of UV phototherapy by real time fluorescence quantitative PCR.
Materials and methods: 24 early MF patients in this study were extracted from the paraffin embedded tissues of DNA before and after ultraviolet phototherapy. The positive controls were positive in the pre experiment, the distilled water was the blank control and the normal human negative control. The changes of the number of BCL-2/IgH copies before and after the treatment were detected by real time fluorescence quantitative PCR method. And the recurrence and curative effect were statistically analyzed to explore the relationship between the efficacy of ultraviolet phototherapy and the prognosis of early MF, and the possible mechanism of phototherapy.
Results: the relative expression of BCL-2/IgH fusion gene (delta CT) P0.05 in the skin lesions of early MF patients was not statistically significant. There was no statistically significant correlation between the up-regulation and down regulation of BCL-2/IgH before and after treatment.
Conclusion: the early MF can reduce the expression of BCL-2 protein with other non specific pathways, not by reducing the copy number of the BCL-2/IgH fusion gene.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R739.5
【参考文献】
相关期刊论文 前10条
1 屠善庆,董平,周平,刘蛰慧;蕈样肉芽肿10例报告[J];北京医学;1999年03期
2 宫立众,张翼军,叶庆佾;蕈样肉芽肿11例临床分析[J];重庆医学;2001年02期
3 黄本晨，郭增清;蕈样肉芽肿瘤16例临床分析[J];福建医药杂志;1994年06期
4 应作霖,孙建方,曾学思,林彤,姜yN群,桑红桂,李阿梅;蕈样肉芽肿的bcl-2、p53和PCNA的蛋白表达[J];临床皮肤科杂志;2000年05期
5 陈明华,陈连军,邱丙森;光化学疗法联合干扰素治疗蕈样肉芽肿30例[J];临床皮肤科杂志;2002年12期
6 姚志远;汪晨;宣红梅;;窄谱中波紫外线治疗早期蕈样肉芽肿9例疗效观察[J];临床皮肤科杂志;2006年06期
7 刘洁;曾跃平;陈金波;张涛;马东来;王宝玺;;蕈样肉芽肿[J];临床皮肤科杂志;2008年02期
8 徐敏;纪岩文;张理涛;纪华安;;蕈样肉芽肿诊断研究进展[J];中国麻风皮肤病杂志;2007年12期
9 郭砚;燕华玲;;蕈样肉芽肿7例临床分析[J];中国麻风皮肤病杂志;2008年02期
10 葛进满,翁孟武;蕈样肉芽肿10例报告[J];现代实用医学;2001年03期
本文编号：2153954
本文链接：https://www.wllwen.com/yixuelunwen/pifb/2153954.html
最近更新
教材专著
