细胞周期素D1和抗原Ki-67在宫颈上皮内瘤样病变和宫颈鳞癌的表达及与人乳头瘤病毒感染转归的关系

目的 研究细胞周期素D1(cyclin D1)、抗原Ki-67在宫颈上皮内瘤样病变(CIN)和宫颈鳞癌发生发展中作用及其与人乳头瘤病毒(HPV)感染转归的关系.方法 2002年1月至2006年12月广州医学院第一附属医院HPV阳性患者104例,分2组:(1)研究组:82例,即病理确诊CIN Ⅰ组17例、CINⅡ组19例、CINⅢ组23例、宫颈鳞癌组23例.(2)对照组:柱状上皮异位22例.应用EnVision法检测宫颈病变组织中cyclin D1、Ki-67蛋白的表达,杂交捕获试验检测宫颈分泌物或阴道残端中HPV感染情况,随访各组患者术后1年内的HPV变化.结果 (1)cyclin D1在各组宫颈组织细胞核内均有表达.其阳性率CINⅢ组[82.61%(19/23)]、宫颈鳞癌组[86.96%(20/23)]与对照组[27.27%(6/22)]、CINⅠ组[58.82%(10/17)]比较,差异有统计学意义(P<0.05),在宫颈鳞癌组与CINⅡ组[68.42%(13/19)]阳性率比较差异有统计学意义(P<0.05).(2)Ki-67在各组宫颈组织细胞核内均有表达,其对照组阳性率[31.82%(7/22)]与CINⅢ组[86.96%(20/23)]、宫颈鳞癌组[91.30%(21/23)]比较差异有统计学意义(P<0.05),而在宫颈鳞癌组与CINⅠ组[58.82%(10/17)]、CIN Ⅱ组[63.16%(12/19)]比较差异有统计学意义(P<0.05).(3)术后1年内各组HPV的转阴率分别与cyclin D1、Ki-67的表达强度呈负相关(rs=-0.299,rs=-0.367,P<0.05).结论 cyclinD1和Ki-67在CIN和宫颈鳞癌的细胞增殖活动中起作用,且两者可能与HPV感染转阴率有关.     

阴茎癌中p53表达与HPV16、18 DNA的检测

目的：研究阴茎癌中p53表达与HPV DNA感染的关系。方法：应用免疫组化技术LSAB法检测33例阴茎癌p53表达及PCR技术检测HPV16、18DNA。结果：33例阴茎癌中，p53阳性表达率51.5%(17/33)；HPV16 DNA阳性率30.3%(10/33)；HPV18 DNA阳性率3.03%(1/33)。结论：阴茎癌中p53表达表明p53突变在阴茎癌发生中有一定意义。阴茎癌发生与HPV16和18型感染有关。     

胃肠道间质瘤中p53、Ki-67、Bcl-2、CyclinD_1的表达及其与预后的关系

目的:分析32例胃肠道间质瘤(GISTs)病人组织切片中p53、Ki-67、Bcl-2和CyclinD1表达及其与预后的相关性。方法:采用免疫组化SABC法检测32例GISTs患者p53、Ki-67、Bcl-2和CyclinD1的表达。结果:p53在良性组均呈阴性,在交界组与恶性组呈阳性者为3例和15例;Ki-67指数在三组中表达分别为(8.97±4.12)%、(16.21±7.44)%和(22.33±9.14)%(P<0.01);Bcl-2在三组呈阳性者分别为2例、3例和12例;CyclinD1指数在三组中表达分别为16.95%、51.22%和69.38%。Ki-67表达大于20%有12例,存活时间平均10.5月,Ki-67表达小于20%的存活时间平均22.4月。结论:Ki-67增值指数不仅可用作评价GISTs恶性潜能的指标,而且Ki-67指数大于20%具有独立的预后意义。     

6例分化型外阴上皮内瘤变临床病理观察

目的：探讨分化型外阴上皮内瘤变( differentiated-type vulvar intraepithelial neoplasia, dVIN)的临床病理学特征、鉴别诊断、治疗及预后。方法回顾性分析6例dVIN的临床特点、病理形态学和免疫表型特征,并复习相关文献。结果患者均为女性,年龄53~80岁,平均62岁,临床特点大多表现为外阴白斑、激惹、瘙痒、疼痛、溃疡、触血。病理组织学特征表现：基底与副基底层显著增生,上皮角下延、吻合,细胞显著异型,核仁明显,核分裂活跃,伴异常角化;中、表层细胞高度分化,细胞间桥显著,伴明显的胞质嗜酸性改变,表层角化过度与角化不全;邻近上皮真皮水肿与胶原化,带状淋巴细胞浸润,表皮增生与角化过度。免疫表型：p53在dVIN中的阳性率为83．3%(5/6),p16不表达(0/6),dVIN基底层和副基底层细胞Ki-67增殖指数>90%。4例随访时间为6~36个月,平均17个月,其中1例术后9个月死亡,1例术后6个月复发,复发和死亡的2例同时或异时伴浸润性鳞状细胞癌,其余2例术后分别随访18个月和36个月,均无复发。结论 dVIN是一种少见的高级别外阴上皮内病变,具有高的、潜在进展危险性,p53、p16及Ki-67联合使用有助于dVIN的诊断。     

p16/Ki-67联合检测对TCT阴性高危型HPV感染者子宫颈病变的诊断价值

目的探讨p16/Ki-67联合检测对TCT阴性的高危型HPV感染者子宫颈病变筛查的应用价值。方法收集2020年5月～2021年1月合肥市第一人民医院妇科收治的高危型HPV且TCT检测阴性的患者150例,经阴道镜取子宫颈组织行病理活检和p16/Ki-67联合检测,以病理活检结果为金标准,分析p16/Ki-67联合检测对筛查子宫颈病变的诊断价值。结果 150例TCT阴性高危型HPV感染患者中,子宫颈阳性病变者62例(41.3%),其中CINⅠ级36例(24%),CINⅡ级20例(13.3%),CINⅢ级5例(3.3%),子宫颈癌1例(0.7%),而达到CINⅡ级以上病变者共26例(17.3%)。p16/Ki-67联合检测阳性率在于子宫颈阴性病变组为12.5%,在子宫颈阳性病变组为69.4%,其中在CINⅠ、Ⅱ、Ⅲ级及子宫颈癌中双阳率分别为:55.6%、85.0%、100%、100%。p16/Ki-67联合检测在CINⅡ级以上病变的敏感度为88.5%,特异度为96.6%,阳性预测值为67.6%,阴性预测值为96.3%。结论 p16/Ki-67联合检测对于子宫颈病变检出具有较高的敏感性和特异性,临床上可提高对TCT阴性高危型HPV感染的子宫颈病变检出率,可用于子宫颈病变的早期筛查,具有一定预警作用。     

p16、p53和Ki-67蛋白在宫颈上皮内瘤变中的表达及意义

目的 探讨p16、p53和Ki-67蛋白在宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)中的表达及临床意义.方法 采用免疫组化SP法检测正常子宫颈或炎性病变组织、CIN1～3中p16、p53和Ki-67蛋白的表达.结果 p16、p53和Ki-67蛋白在正常子宫颈或炎性病变中罕见表达,在CIN1～3组织中三者表达均较高,随CIN级别升高p16、p53和Ki-67表达增强,各组间表达差异有统计学意义(P<0.05).同时p16、p53和Ki-67三者阳性表达均可见分层现象,在CIN1中大部分阳性细胞位于子宫颈鳞状上皮的下1/3,在CIN2中多累及上皮下2/3,而CIN3则普遍超过上皮的下2/3或全层弥漫阳性,各组间差异具有统计学意义(P<0.05).结论 p16、p53和Ki-67蛋白表达均与子宫颈上皮内瘤变的病变进展密切相关,联合检测p16和Ki-67的抗原表达可作为CIN分级诊断的辅助方法,具有较好的应用价值.     

宫颈上皮内瘤变及宫颈鳞癌中cyclin D1、Ki-67的表达及其意义

目的： 检测细胞周期素D1（cyclin D1）、增殖细胞核抗原（Ki-67）在人乳头瘤病毒（HPV）感染患者宫颈上皮内瘤样病变（CIN）及宫颈鳞癌中的表达及其相关性,研究其在CIN及宫颈鳞癌发生及发展过程中的作用。方法: 研究组HPV阳性病理确诊CINⅠ17例、CINⅡ19例、CINⅢ23例、宫颈鳞癌23例,对照组HPV阳性病理确诊柱状上皮异位22例。应用免疫组化S-P法检测宫颈病变组织中cyclin D1、Ki-67蛋白的表达,杂交捕获二代检测宫颈分泌物中HPV感染的情况。结果: (1)Cyclin D1在5组宫颈组织细胞的细胞核内均有表达,CINⅢ组、宫颈鳞癌组与对照组比较差异显著（P<0.05）,CINⅢ组、宫颈鳞癌组与CINⅠ组比较差异显著（P<0.05）,宫颈鳞癌组与CINⅡ组比较差异显著（P<0.05）。(2)Ki-67在5组宫颈组织细胞的细胞核内均有表达,对照组与CINⅢ组比较差异显著（P<0.05）,对照组与宫颈鳞癌组比较差异显著（P<0.05）,CINⅠ组与宫颈鳞癌组比较差异显著（P<0.05）,CINⅡ组与宫颈鳞癌组比较差异显著（P<0.05）。(3)Cyclin D1、Ki-67在CIN及宫颈鳞癌中的表达强度呈正相关关系 （P<0.05）。结论: Cyclin D1和Ki-67在CIN和宫颈鳞癌发生发展及细胞增殖活动中起一定的作用;两者在CIN和宫颈鳞癌的发生发展中可能发挥协同作用。     

P16、Ki-67和Bcl-2在宫颈上皮内瘤变中的表达及应用

目的探讨P16、Ki-67、Bcl-2抗体在宫颈上皮内瘤变(CIN)中的表达及应用价值。方法用快捷免疫组化染色法检测30例正常宫颈组织和66例CIN中p16、Ki-67和Bcl-2的表达,分析比较两组的标记结果。结果 CIN中p16、Ki-67、Bcl-2的阳性率显著高于正常宫颈(﹤0.05),CINⅡ-Ⅲ的表达率显著高于CINⅠ(﹤0.05)。结论 P16、Ki-67和BCL-2抗体联合标记可作为病理诊断CIN和区分级别的重要参考指标。     

HPV感染和p53异常表达与宫颈鳞癌的关系

目的研究宫颈鳞癌与p53蛋白表达和HPV感染的关系,探讨宫颈鳞癌的形成机制。方法采用RT-PCR法分别检测p53基因在39例宫颈鳞癌组织和39例正常宫颈黏膜组织中的表达情况以及PCR方法检测HPV在这些组织中的感染情况。结果 HPV在宫颈鳞癌组中阳性率为48.72%(19/39),正常组织中为14.81%(4/27),p53基因表达在宫颈鳞癌组中阳性率为53.85%(21/39),正常组织中为18.52%(5/27),宫颈癌组的HPV感染和p53表达均高于正常组(P0.05)。结论 HPV感染与p53基因的异常表达与宫颈鳞癌发生密切相关,联合检测能提高准确性。     

RANTES在HPV感染的子宫颈鳞癌及癌前病变中的表达

目的 探讨趋化因子RANTES在人乳头瘤病毒(HPV)感染的子宫颈鳞癌及癌前病变中的表达.方法 用免疫组化方法 对133例HPV阳性病例子宫颈组织中趋化因子RANTES进行检测.其中正常子宫颈组织10例,子宫颈上皮内瘤变Ⅰ、Ⅱ、Ⅲ级各30例,子宫颈鳞癌33例.结果 RANTES在子宫颈鳞癌组的阳性表达率较CIN组和正常对照组显著增高(P<0.01),其阳性表达强度亦较CIN组和正常对照组显著增高(P<0.01).CIN组内的阳性表达率和阳性表达强度随分级升高而增高,且各组之间比较差异均具有统计学意义(P<0.05);CINⅢ组的阳性表达率和阳性表达强度较正常对照显著增高(P<0.05);CINⅠ、Ⅱ与正常组比较其阳性表达率和阳性表达强度均无统计学意义(P>0.05).结论 RANTES与HPV感染的子宫颈鳞癌及癌前病变密切相关.     

外阴营养不良、外阴鳞状上皮细胞癌凝集素标记免疫组化分析

目的：探讨外阴营养不良增生型,硬化苔藓型表皮细胞和外阴鳞状上皮细胞癌等细胞膜结构与凝集素受体结合表达特征及它们三者之间的关系。方法：对慢性外阴营养不良表皮增生型,苔藓硬化型及外阴鳞状上皮细胞癌3种状态下的细胞进行了8种凝集素免疫组织化学标记,分析,比较。结果：外阴营养不良增生型表皮各层细胞细胞膜与刀豆凝集素（ConA),扁豆凝集素（LCA）,花生凝集素（PNA）,蓖麻凝集素（RCA－1）和大豆凝集素（SBA）结合强度弱,其表皮细胞细胞核膜与ConA,PNA和麦胚凝集素（WGA）有中等强度结合,外阴营养不良硬化苔藓型表皮各层细胞细胞膜与ConA,RCA-1 SBA和WGA结合强度弱,而与LCA不结合,其12例中的8例与荆豆凝集素（UEA－1）发生较弱的结合,外阴鳞状上皮细胞癌癌细胞与8种凝集素均结合,其12例中的7例其癌细胞膜与双花扁豆凝集素（DBA）弱结合,癌细胞膜与UEA－1强结合,但癌巢中央细胞团不与UEA－1结合,癌细胞细胞核膜与ConA,LCA,RCA-1呈强结合。结论：凝集素标记免疫组织化学染色可作为诊断,鉴别诊断外阴营养不良增生,硬化苔藓型和外阴鳞状上皮细胞癌新的指标,具有恶变潜能的增生型外阴营养不良与外阴鳞状上皮细胞癌,两者细胞核膜凝集素标记有相似之处,提示在外阴组织的癌变过程中,细胞核膜凝集素标记的异常表达是一个早期标识,糖基和糖蛋白代谢的异常可能是细胞发生癌变最早期的表现之一。     

p53 immunostaining in lichen sclerosus is related to ischaemic stress and is not a marker of differentiated vulvar intraepithelial neoplasia (d-VIN)

AIM: To analyse p53 immunoreactivity in 207 biopsy specimens of lichen sclerosus (LS) and "differentiated vulvar intraepithelial neoplasia" (d-VIN), a postulated precursor lesion for LS-associated vulvar squamous cell carcinoma (SCC), which is characterized by atypical basal keratinocyte proliferations with p53+ basal/suprabasal keratinocyte nuclei. METHODS AND RESULTS: Forty early, 78 classic, 30 hypertrophic vulvar LS, 26 paediatric vulvar and penile LS, 33 vulvar LS-associated SCC and 30 vulvar/penile control specimens were examined for p53 expression and the presence of d-VIN. Nuclear p53 staining was observed in 175/207 LS biopsy specimens. Eighty percent of early and 69% of paediatric LS showed discontinuous/continuous p53 staining in basal keratinocytes. Classic LS showed no p53 staining in 17%, discontinuous basal keratinocyte staining in 20%, continuous basal keratinocyte staining in 58%, basal/suprabasal staining in 5%. Hypertrophic LS revealed basal keratinocyte staining in 32% and basal/suprabasal staining in 61%. p53 staining was associated with sclerosis of blood vessels and dermis, lymphoid infiltrates, vasculitis and hypertrophic LS. d-VIN was seen in 2% of LS alone and in 24% of LS-associated SCC. CONCLUSION: d-VIN in LS is rare, while p53 staining is common and best explained as an ischaemic stress response due to poor oxygenation, vasculitis and inflammation rather than as a marker of a precancerous lesion in LS.     

328例女阴营养不良的病理分析

主张采用1975年国际外阴疾病研究协会上通过的女阴营养不良的命名及其分类。此法简易可行,能反映疾病的本质及其生物学行为。本文对内蒙古地区328例女阴营养不良作了病理分析,发现增生性营养不良156例(47.6%),萎缩性营养不良113例(34.6%),发病率偏高于国内其他地区,好发年龄均在20～30岁之间。病理所见,不仅上皮组织中有明显的营养不良改变,在真皮层内的结缔组织、神经组织及皮肤附属器亦均出现程度不等的变性、萎缩和消失。认为这些均系血管改变的结果。     

Specific intraepithelial localization of mast cells in differentiated vulvar intraepithelial neoplasia and its possible contribution to vulvar squamous cell carcinoma development

van de Nieuwenhof H P, Hebeda K M, Bulten J, Otte‐Holler I, Massuger L F A G, de Hullu J A & van Kempen L C L T
(2010) Histopathology 57, 351–362
Specific intraepithelial localization of mast cells in differentiated vulvar intraepithelial neoplasia and its possible contribution to vulvar squamous cell carcinoma development Aims: The aetiology of vulvar squamous cell carcinomas (SCC) that are not causally associated with high‐risk human papillomavirus remains largely elusive. The aim of this study was to analyse the inflammatory response in its presumed precursor lesions, lichen sclerosus (LS) and differentiated vulvar intraepithelial neoplasia (dVIN), and provide evidence that dVIN is a likely precursor of vulvar SCC. Methods and results: Immunohistochemical analyses for CD4+, CD8+, CD20+, CD68+, S100+ and tryptase‐positive immune cells were performed and quantified in LS (n = 7), dVIN (n = 19), SCC (n = 11), and normal vulvar tissue (n = 8). The subepithelial inflammatory response in dVIN and SCC was comparable, but absent in LS. Abundant intraepithelial mast cells were observed in dVIN only, and confirmed by electron microscopy, toluidine blue staining and cKIT expression. Adjacent keratinocytes displayed increased proliferation as determined by MIB‐1 positivity. Electron microscopy revealed intraepithelial mast cell degranulation. Intraepithelial mast cells were not or infrequently observed in vulvar hyperplasia (n = 13), condylomata acuminata (n = 5), keratinocytic intraepidermal neoplasia of sun‐exposed skin (n = 15), epidermal hyperplasia of head and neck (n = 12), and psoriasis (n = 3). Conclusions: These data indicate that dVIN can be recognized by intraepithelial mast cells and that they might promote the progression of dVIN to SCC.     

Histopathological work-up and interpretation of sentinel lymph nodes removed for vulvar squamous cell carcinoma

Aims:  To evaluate the work-up of sentinel lymph nodes (SLNs) removed for vulvar pT1–pT2 squamous cell carcinoma (SCC). Inguinal lymphadenectomy yields metastases in only 30% of cases. Patients with missed inguinal disease, however, have a risk of dying from systemic disease. SLN dissections reduce morbidity, but work-up should reliably identify metastatic disease.
Methods and results:  All SLNs removed from 38 patients with pT1–pT2 SCC and clinically negative inguinal lymph nodes were submitted for frozen section analysis. When negative, SLN were formalin-fixed, sectioned entirely at 330-μm intervals to produce three slides per millimetre [two haematoxylin and eosin (H&E) stained slides; one slide for immunohistochemistry]. If screening of H&E-stained sections was negative, all remaining slides were subjected to immunohistochemistry with an antibody to cytokeratin. Twenty-five of 38 patients (66%) were pN0, 7/38 (18%) had metastases on frozen sections/H&E stains. Immunohistochemistry detected micrometastases in two patients and single tumour cells and anucleate cell structures in four patients. In 12/13 patients the SLN metastases, including all single-cell deposits, were from lichen sclerosus (LS)-associated SCC. Twelve of 13 patients with metastases had a pT2 SCC.
Conclusions:  Micrometastases and single tumour cell deposits in SLNs are typical of LS-associated vulvar SCC. Single tumour cell deposits in SNLs should be regarded as 'positive'. Identification requires serial sectioning and immunohistochemical analysis of all removed SLNs.     

Morphometric analysis of nuclear/cytoplasmic ratios in normal and perineoplastic vulvar skin

Analysis of vulvar skin adjacent to squamous carcinoma has demonstrated abnormal deoxyribonucleic acid (DNA) content in histologically unremarkable specimens. Analysis of DNA by microdensitometry is time-consuming. Morphometric analysis by point counting was used to compare the nuclear/cytoplasmic ratios of normal vulvar skin and skin adjacent to malignancy. This showed elevated ratios in the latter specimens although there was no linear relationship to increasing ploidy.     

血管肌纤维母细胞瘤临床病理特征

目的：探讨血管肌纤维母细胞瘤的临床病理形态特征及鉴别诊断。方法：对2例血管肌纤维母细胞进行组织病理学、免疫组织化学研究,结合文献资料分析本病的临床表现、病理形态特点及鉴别诊断。结果：血管肌纤维母细胞瘤呈大片黏液背景、丰富薄壁海绵样血管和梭形上皮样细胞即肌纤维母细胞,后者胞质丰富,呈嗜酸性,核卵圆或杆状,两端对称变细或稍钝,瘤细胞分布有明显的疏密区,密集区聚于血管周围,成束或链状排列、疏松区弥散于黏液背景中,且瘤细胞常与胶原纤维伴行。结论：血管肌纤维母细胞瘤为良性肿瘤,好发于女性外生殖器,起源与肌纤维母细胞相关,既向纤维,又向平滑肌分化,且伴有丰富的海绵样薄壁血压和间质黏液变性。