宫颈癌与宫颈病变组织AuroraA和AuroraB表达与临床病理因素相关性分析

目的：探讨宫颈病变组织中AuroraA、B的表达与临床病理因素的相关性。方法：2010—09—012012—06—30河北医科大学第一医院门诊及住院确诊的204例宫颈病变组织,其中慢性宫颈炎40例,CINI52例,CINⅡ～Ⅲ级48例,宫颈鳞状上皮细胞癌64例。采用免疫组化法检测宫颈组织中AuroraA、B的表达,分析AuroraA、B在不同宫颈组织中表达的意义及其与临床病理特征间的关系。结果：AuroraA在慢性宫颈炎组、CINI组、CINⅡ～Ⅲ组及宫颈鳞癌组中的阳性表达率分别为2．50％（1／40）、11．54％（6／52）、62．50％（30／48）和78．69％（51／64）,AuroraB分别为2．50％（1／40）、9．62％（5／52）、58．33％（28／48）和68．75％（44／64）。AuroraA、B的阳性表达率在cINⅡ～Ⅲ组及宫颈鳞癌组明显高于慢性宫颈炎组和CINI组,P〈0．001;但在宫颈鳞癌与CINⅡ～Ⅲ中的表达差异无统计学意义,P值分别为0．070和0．255。AuroraA表达与宫颈癌的临床分期（P=0．030）、淋巴转移（P一0．040）和肿瘤细胞分化程度（P=0．009）有关,AuroraB的表达与肿瘤细胞分化程度有关,P=0．007。AuroraA、B的表达呈正相关,P〈0．001。结论：AuroraA和AuroraB表达与宫颈癌的发生、发展密切相关,有望成为宫颈癌早期诊断、治疗的生物学指标。     

凋亡相关蛋白3（APR3）在宫颈鳞癌组织中的表达及临床意义

目的：探讨 APR3在不同宫颈组织的表达情况和临床病理意义。方法：免疫组化法（SP 法）对放化疗前后的宫颈鳞癌组织80例,CIN 90例以及正常宫颈组织30例的 APR3表达情况进行检测。结果：APR3在宫颈鳞癌中阳性表达率为81．25％,明显高于 CIN 组的31．11％以及对照组的10．00％（P ＜0．01）。放化疗后宫颈鳞癌组织中 APR3的表达率为51．25％,低于放化疗前81．25％（P ＜0．01）。APR3阳性表达率随临床分期的增高而增加（P ＜0．05）,病理分化程度的降低而增加（P ＜0．05）,有淋巴结转移者阳性表达率明显高于无转移者（P ＜0．05）。结论：APR3与子宫颈病变良恶性有关,与子宫颈鳞癌发生发展相关。放化疗可能影响宫颈鳞癌组织中 APR3的表达水平。     

宫颈腺癌中FHIT蛋白表达与HPV感染的研究

目的 探讨脆性组氨酸三联体（FHIT）基因在官颈腺癌发生发展中的作用，分析FHIT蛋白表达与人乳头瘤病毒（HPV）感染的关系。方法 采用组织微阵列技术结合免疫组化（二步法）检测FHIT蛋白与HPVl6／18E6蛋白在86例宫颈腺癌组织和24例慢性宫颈炎组织中的表达。结果 FHIT蛋白在宫颈腺癌组织中的阳性表达率为46．5％，较慢性宫颈炎组织100．0％明显降低（P〈0．01）；HPVl6／18-E6蛋白阳性表达率为65．1％，明显高于慢性宫颈炎组织4．2％（P〈0．01）。FHIT蛋白表达与宫颈腺癌病理分级和组织学类型有关，G2、G3组FHIT阳性表达率为39．4％和22．7％，均明显低于G1组（P〈0．05），透明细胞腙癌FHIT阳性表达率为22．2％，明显低于其它类型宫颈腺癌（P〈0．05）。HPVl6／18-E6蛋白表达与宫颈腺癌病理分级和组织学类型无关（P〉0．05）。结论 宫颈腺癌的发生发展与HPV感染及FHIT表达缺失密切相关。     

宫颈液基细胞学标本中p16^INK4A的表达

[目的]探讨p16^INK4A在新柏氏宫颈液基细胞学（TCT）标本中各级宫颈上皮内瘤变的表达，评价其在宫颈病变中表达的意义。[方法]采用Envision法，检测76例TCT标本及相应宫颈活检组织中p16^INK4A表达。[结果]在TCT中，P16^INK4A在无上皮内病变（NILM）、非典型鳞状细胞（ASC）、低级别鳞状上皮内病变（LSIL）、高级别鳞状上皮内病变（HSIL）阳性表达率分别为0、15．78％、45．45％、88％。在相应活检组织中，p16^INK4A在宫颈炎、CINI、CINⅡ、CINⅢ中阳性表达率分别为0、63．15％、89．28％、100％。p160^INK4A在TCT和相应活检组织中表达的符合率为91.23％。[结论]TCT标本的p16^INK4A表达检测可以提高宫颈高级别病变的检出率。     

宫颈腺癌HPV16／18感染与ki67、p53蛋白表达的关系

目的研究人宫颈腺癌组织中ki67、p53蛋白表达,分析HPV16／18感染与ki67、p53蛋白表达的关系。方法采用组织微阵列技术结合原位杂交和免疫组化（二步法）检测24例慢性宫颈炎和86例宫颈腺癌HPV16／18-E6DNA和ki67、p53蛋白表达情况。结果HPV16／18-E6DNA与ki67、p53蛋白表达在宫颈腺癌组织中的阳性率分别为65．1％、51．2％、45．3％,均显著高于慢性宫颈炎组织8．3％、0．0％、0．0％（P〈0．01）。HPV16／18感染与宫颈腺癌的病理分级和组织学类型无关,但与ki67表达呈正相关（P〈0．05）,与p53表达呈负相关（P〈0．05）。ki67、p53蛋白表达与宫颈腺癌的病理分级有关,G2、G3组阳性表达率均明显高于G1组（P〈0．05）。ki67、p53蛋白表达与宫颈腺癌组织学类型无相关性。结论宫颈腺癌的发生发展与HPV16／18感染及ki67、p53蛋白表达异常相关。     

宫颈脱落细胞p16^INK4A和p57^KIP2

目的：研究p16^INK4A和p57^KIP2在宫颈脱落细胞的表达及其与临床病理指标的关系。方法：采用免疫细胞化学二步法，检测81例不同病变阶段的宫颈脱落细胞标本中p16^INK4A和p57^KIP2的表达。结果：p16^INK4A在ASC—US、低级别上皮内病变（CINⅠ）、高级别上皮内病变（CINⅡ～Ⅲ）和浸润性癌的阳性表达率分别为6．25％（1／16）、58．8％（10／17）、89．2％（33／37）和100．0％（11／11），各组之间的差异有统计学意义，χ^2=38．806，P〈0．001；p57^KIP2在高级别上皮内病变（CINⅡ～Ⅲ）和浸润性癌的阳性表达率为27．1％（13／48），与ASC—US和低级别上皮内病变（CINⅠ）的阳性表达率为69．7％（23／33）比较，差异有统计学意义，χ^2=15．194，P=0．002。结论：p16^INK4A和p57^KIP2在宫颈脱落细胞中的表达与临床病理指标密切相关，p16^INK4A和p57^KIP2可以作为宫颈癌前病变高危人群的筛查指标。     

宫颈脱落细胞p16INK4A和p57KIP2表达及其临床意义的初步探讨

目的：研究p16^INK4A和p57^KIP2在宫颈脱落细胞的表达及其与临床病理指标的关系。方法：采用免疫细胞化学二步法，检测81例不同病变阶段的宫颈脱落细胞标本中p16^INK4A和p57^KIP2的表达。结果：p16^INK4A在ASC—US、低级别上皮内病变（CINⅠ）、高级别上皮内病变（CINⅡ～Ⅲ）和浸润性癌的阳性表达率分别为6．25％（1／16）、58．8％（10／17）、89．2％（33／37）和100．0％（11／11），各组之间的差异有统计学意义，χ^2=38．806，P〈0．001；p57^KIP2在高级别上皮内病变（CINⅡ～Ⅲ）和浸润性癌的阳性表达率为27．1％（13／48），与ASC—US和低级别上皮内病变（CINⅠ）的阳性表达率为69．7％（23／33）比较，差异有统计学意义，χ^2=15．194，P=0．002。结论：p16^INK4A和p57^KIP2在宫颈脱落细胞中的表达与临床病理指标密切相关，p16^INK4A和p57^KIP2可以作为宫颈癌前病变高危人群的筛查指标。     

hTERC和高危HPV及细胞学联合检测在宫颈癌筛查中的价值

目的：探讨联合应用hTERC、高危HPV检测及液基细胞学检查TCT在宫颈癌筛查中的意义。方法：选择2010年5月至2012年1月因宫颈异常在佛山市妇幼保健院宫颈门诊行TCT检查的患者100例为研究对象,同时行HC2检测高危HPV感染,FISH技术检测hTERC基因扩增及阴道镜下病理活组织检查,以病理学结果为金标准,将三种检测方法的结果与其进行比较。结果：非CIN组、CIN1、高级别CIN及浸润癌中TCT检查与病理学结果符合率分别为88．9％（16／18）、58．33％（14／24）、68．29％（28／41）、76．47％（13／17）,高危HPV阳性率分别为27．78％（5／18）、91．67％（22／24）、97．56％（40／41）、100％（17／17）,hTERC阳性率分别为11．1％（2／18）、29．17％（7／24）、87．80％（36／41）、100％（17／17）。随着宫颈病变病理级别的递增,高危HPV的表达及hTERC基因扩增出现递次增高。非CIN组高危HPV感染率低于CIN组,差异有统计学意义（P〈0．01）,CIN1、CIN2及CIN3三组间比较差异无统计学意义（P〉0．05）,CIN组与宫颈浸润癌组差异无统计学意义（P〉0．05）。hTERC基因扩增率高级别CIN组及浸润癌组明显高于低级别CIN1组（P〈0．01）。结论：在宫颈癌筛查中,细胞学检查具有较高的特异性（92．5％）,但灵敏度较差（53．4％）,高危HPV检测灵敏度高（96．7％）,但特异性差（44．6％）,hTERC基因扩增筛查高级别CIN病变特异性高（98．6％）,灵敏度稍低（71．7％）,在宫颈组织的表达率与宫颈病变程度密切相关,三种方法联合检测可以大大提高宫颈癌前病变的阳性检出率,有利于较特异地识别出具有较高的转化为宫颈癌潜能的高级别CIN病变。     

人乳头瘤病毒感染对宫颈腺癌中p27^kip1蛋白表达的影响

目的探讨人乳头瘤病毒（HPV）感染对宫颈腺癌中细胞周期调控因子p27^kip1蛋白表达的影响以及二者在宫颈腺癌发生过程的作用。方法采用原位杂交和免疫组化（二步法）检测24例慢性宫颈炎和86例宫颈腺癌组织的HPV16／18DNA和p27^kip1蛋白表达情况。结果HPV16/18DNA在宫颈腺癌组织中的阳性率为65．1％，显著高于慢性宫颈炎组织8．3％（P〈0．01）。p27^kip1蛋白表达在宫颈腺癌组织中的阳性率为55．8％，明显低于慢性宫颈炎组织79.2％（P〈0．05）．HPV16／18感染与宫颈腺癌的组织学类型无关，但与p27^kip1表达呈负相关（P〈0．05）。p27^kip1表达与官颈腺癌组织学类型有明显相关性，透明细胞腺癌p27^kip1阳性表达率明显低于其它类型宫颈腺癌（P〈0．05）。结论HPV16／18感染可能引起p27^kip1蛋白表达异常，从而导致宫颈腺癌发生。     

MMP-2和TIMP-2在宫颈腺癌中的表达及与其转移的关系

目的：研究宫颈腺癌组织中基质金属蛋白酶（MMP）和金属蛋白酶组织抑制因子（TIMP）的表达及其与肿瘤浸润转移的关系，揭示宫颈腺癌的浸润转移机制。方法：应用免疫组化方法，检测了10例慢性宫颈炎和63例宫颈腺癌组织中MMP－2和TIMP－2的表达情况。结果：MMP－2和TIMP－2在慢性宫颈炎组织中均无阳性表达，而在宫颈腺癌组织中阳性表达率分别为73．0％（46／63）和82．5％（52／63），有显著性差异。MMP－2在腺型腺癌和乳头状腺癌组织中阳性表达率分别为81．8％（18／22）和58．3％（14／24），无显著性差异，而MMP－2和TIMP－2表达与其临床分期也无相关性（P＞0．05）。MMP－2和TIMP－2表达间有非常显著相关性（P＜0．01），同时MMP－2阳性表达与该肿瘤转移呈正相关（P＜0．05）。结论：MMP－2可作为预测肿瘤浸润和转移的1个指标。     

维吾尔族妇女宫颈病变病理进程与降钙素相关肽α表达的关系

目的：观察降钙素相关肽α（calcitonin-related polypeptide alpha,CALCA）的蛋白表达水平与宫颈病变病理进程的关系。方法：收集维吾尔族妇女宫颈炎、低度鳞状上皮内瘤变（LSIL）、高度鳞状上皮内瘤变（HSIL）和宫颈鳞癌（CSCC）患者的石蜡包埋组织标本共104例,采用免疫组织化学方法检测CALCA蛋白的表达水平。结果：CALCA蛋白在大部分宫颈炎患者的宫颈上皮细胞中强表达,但是随着宫颈上皮内瘤变和宫颈癌的发生,其表达水平呈现从强表达到弱表达或表达缺失的趋势改变,且与宫颈病变病理进程呈负相关（r=-0.361,P〈0.01）,其中宫颈炎、LSIL、HSIL和CSCC组患者的CALCA蛋白表达缺失率分别为45.5%（15/33）、75%（12/16）、80.8%（21/26）和82.8%（24/29）,C ALCA蛋白表达缺失率在HSIL及CSCC与宫颈炎间的差异具有统计学意义（P〈0.01）,而在LSIL与宫颈炎间的差异无统计学意义（P〉0.05）。结论：CALCA蛋白表达缺失与维吾尔族妇女宫颈癌前病变及癌症的发生有一定的关系。     

Distinction of low-grade squamous intraepithelial lesions from high-grade squamous intraepithelial lesions based on quantitative analysis of proliferative activity

The management of cervical dysplasia is determined by the grade of SIL (LSIL, conservative management; HSIL, ablative/excisional therapy). The grading, however, is subjective and its reproducibility is low. This study evaluates if quantitative differences in mitotic activity and MIB-1 expression (ME) in LSIL and HSIL are helpful in their discrimination. Twenty-seven cervical biopsies with LSIL and 16 with HSIL were immunostained for MIB-1. ME was evaluated in 100 contiguous cells of lesional squamous epithelium in basal layer, lower-third, middle-third, and upper-third, in areas with highest staining. Mitoses were counted in 10 contiguous high power fields in areas with the highest mitotic activity (mitotic index, MI). MI was significantly increased in HSIL (mean 27.5) as compared to LSIL (mean 14.3). MI at cut-off values < or =10 and > or =25, favored a diagnosis of LSIL, and HSIL, respectively. ME, in all four layers, was significantly greater in HSIL vs. LSIL. ME in the basal and the upper-third layer proved useful in grading SIL with equivocal MI: all LSIL cases with MI >10 had <30% of ME in the basal layer; and all, except one, had <30% of ME in the upper-third; all, except one HSIL cases with MI <25 had >30% of ME in either the basal or the upper-third layer. MI and ME (percentage) appear helpful in grading equivocal SIL cases.     

Active and passive smoking,high-risk human papillomaviruses and cervical neoplasia

Few studies have evaluated the role of passive smoke exposure and cervical neoplasia risk. We assessed the role of active and passive cigarette smoke exposure and risk of cervical squamous intraepithelial lesion (SIL) in a case-control study based in a South Carolina Health Department; 59 high-grade SIL (HSIL) cases, 313 low-grade SIL (LSIL) cases and 427 controls were recruited and interviewed. Passive cigarette smoke exposure was significantly (P < 0.05) associated with high grade SIL (adjusted odds ratio (aOR) = 2.2) and low-grade SIL (aOR = 1.4). Active smoking was associated with SIL only among White women (aOR = 1.8). High-risk human papillomaviruses (HR-HPVs) appear to interact with active cigarette smoking to increase HSIL risk. HSIL cases compared with LSIL cases were significantly more likely to be HR-HPV positive current smokers (aOR = 3.0; 95% CI: (1.2, 7.7)). These data suggest that active and perhaps passive smoke exposure may be important co-factors in HSIL development among HR-HPV positive women.     

去泛素化酶USP9X在宫颈鳞癌中的表达及临床意义

目的:探讨X染色体连锁的泛素特定蛋白水解酶9（ubiquitin-specific peptidase 9 X-linked,USP9X）在宫颈鳞癌中的表达及临床意义。方法:应用EnVision法免疫组织化学技术对宫颈无上皮内瘤变或其他恶性病变组织（negative for intraepithelial lesion or malignancy,NILM）、低级别上皮内瘤变（lower grade squamous intraepithelial lesion,LSIL）、高级别上皮内瘤变（high grde squmous intrepithelil lesion,HSIL）各40例及宫颈鳞癌（cervical squamous-cell carcinoma,CSCC）标本85例中的USP9X蛋白水平进行检测;蛋白印迹法（Western-Blot）检测宫颈癌细胞SiHa中USP9X蛋白的水平。结果:USP9X从宫颈正常上皮到宫颈鳞癌的逐级病变中其表达水平逐步升高: NILM（5.0%）、LSIL（12.5%）、HSIL（40.0%）、CSCC（60.0%）;SiHa细胞培养中,顺铂(C-DDP)处理组USP9X蛋白表达水平较对照组明显降低。结论:USP9X表达的上调可能参与了宫颈癌的发生与发展,可作为宫颈癌治疗时重要参考及预后指标,有望成为宫颈癌的一个潜在治疗靶点。     

Reducing or eliminating use of the category of atypical squamous cells of undetermined significance decreases the diagnostic accuracy of the Papanicolaou smear

BACKGROUND: The diagnosis of "atypical squamous cells of undetermined significance" (ASCUS) is controversial, not only for the clinical utility of its subcategories (favor reactive vs. favor dysplasia), but for its very existence as an expression of uncertainty. In the current study, the authors investigated the impact of reducing and eliminating this category on the sensitivity and predictive values for detecting squamous intraepithelial lesions (SILs).METHODS: One hundred cervical Papanicolaou (Pap) smears originally diagnosed as ASCUS, all of which had histologic follow-up, were reviewed blindly and reclassified as either negative (within normal limits/benign cellular changes), low-grade SIL (LSIL), or high-grade SIL (HSIL) by 1 reviewer who eliminated ASCUS as a diagnostic possibility entirely. A second reviewer reinterpreted the cases but attempted to use the ASCUS diagnosis (favor reactive or favor dysplasia) sparingly. All histologic diagnoses were reviewed, and an adjudicated final diagnosis was established. Reviewed smear interpretations were correlated with the histologic diagnosis (original, reviewed, and adjudicated). Statistical analysis was performed using the Fisher exact test.RESULTS: Thirty-eight women had histologically confirmed SIL (21 LSIL cases and 17 HSIL cases [including 1 case of endocervical adenocarcinoma]); 31 of these 38 cases originally were classified as ASCUS, not otherwise specified, 1 case was classified as ASCUS favor reactive, and 6 cases were classified as ASCUS favor dysplasia. The reviewer who used the ASCUS diagnosis sparingly reclassified the smears as negative (62 cases); ASCUS, favor reactive (3 cases); ASCUS, favor dysplasia (13 cases); LSIL (19 cases); and HSIL (3 cases). The reviewer who eliminated the ASCUS category reclassified the smears as negative (59 cases), LSIL (29 cases), and HSIL (12 cases). The rate of SIL/HSIL in those cases interpreted as abnormal was 38%/17% originally, 42%/24% with a reduced ASCUS interpretation, and 37%/17% when the ASCUS category was eliminated. In those ASCUS smears that were reclassified as negative, the SIL/HSIL rate was 35%/13% with the reduced ASCUS interpretation and 39%/17% when the ASCUS category was eliminated. The sensitivity for detecting a SIL/HSIL was reduced from 100%/100% for the original ASCUS interpretation to 42%/53% for the reduced ASCUS interpretation to 39%/41% with the elimination of the ASCUS interpretation.CONCLUSIONS: Although in the current study utilization of the ASCUS diagnosis was found to result in a 62% negative or reactive outcome on biopsy, a significant number of patients with SIL were detected (38% in the current series, 17% with HSIL). Despite the improved correlation with negative biopsies, reducing or eliminating the ASCUS diagnosis appears to decrease the sensitivity of the Pap smear significantly and appears to be no better than chance at predicting a diagnosis of SIL on biopsy, including HSIL.     

Quantitative methylation-specific PCR for the detection of aberrant DNA methylation in liquid-based Pap tests

BACKGROUND: Aberrant promoter methylation of selective tumor suppressor genes has been detected in squamous intraepithelial lesions (SIL) and invasive cervical cancer. Identification of methylation profiles of genes that can distinguish high-grade SIL (HSIL) from low-grade SIL (LSIL), and cytologically negative for intraepithelial lesion or malignancy (NILM) residual liquid-based Papanicolaou (Pap) tests may be potentially useful as an ancillary test for cervical cancer screening. METHODS: Using real-time quantitative methylation-specific polymerase chain reaction (PCR) (QMSP), the authors analyzed the frequency and relative level of promoter methylation for DAPK1, IGSF4, SPARC, and TFPI2 in biopsy-confirmed HSIL and LSIL, and NILM residual liquid-based Pap tests. The percentage of methylation (%M) for each gene was calculated using the reference gene, ACTB. The cumulative methylation score for each sample, defined as the sum of %M of all 4 genes, was used to analyze the genes in combination. RESULTS: For each gene analyzed the frequency and relative level of methylation were increased in HSIL compared with combined NILM/LSIL samples. The cumulative methylation scores were significantly higher in HSIL samples (P < .0001). Area under the receiver operating characteristic (ROC) curve (AUC) demonstrated that methylation of each gene could distinguish HSIL from NILM/LSIL samples (AUC range, 0.6-0.67; P < or = .0028). The combination of 4 genes showed improved test performance (AUC = 0.76; P < .0001). There was no significant difference in cumulative methylation in HSIL cases with histologic outcomes of cervical intraepithelial neoplasia grade 2 (CIN2) versus CIN3. There was no association between the methylation of any gene and the presence of human papillomavirus. CONCLUSIONS: The methylation profile of multiple genes in combination can better distinguish HSIL from combined NILM/LSIL samples. Although aberrant DNA methylation has the potential to function as a molecular biomarker of HSIL in liquid-based Pap tests, additional genes that are selectively methylated in HSIL are needed to improve the clinical performance.     

AIM2在宫颈癌组织中的表达及其与HPV16病毒载量的相关性分析

目的:研究AIM2与HPV16病毒载量在宫颈癌及其癌前病变组织中的关系。方法:通过免疫组化检测正常宫颈组织(50例)、LSIL(56例)、HSIL(108例)及宫颈癌组织(145例)中AIM2表达,采用实时荧光定量PCR法(硕世21 HPV 分型定量检测系统,BMRT)检测所有纳入患者HPV16型DNA病毒载量,分析AIM2蛋白表达水平、HPV16病毒载量在宫颈癌及其癌前病变中有无差异以及AIM2蛋白表达水平与HPV16病毒载量的相关性。结果:AIM2在正常宫颈组、LSIL组、HSIL组、宫颈癌组中的阳性表达率分别为12.0%（6/50）、26.8%（15/56）、82.4%（89/108）、84.1%（122/145）,呈逐渐增高趋势,差异有统计学意义(χ2=207.675,P＜0.001)。HPV16在正常宫颈组、LSIL组、HSIL组、宫颈癌组中的阳性表达率分别为16.0%（8/50）、30.4%（17/56）、44.4%（48/108）、47.6%（69/145）,呈逐渐增高趋势,差异有统计学意义(χ2=18.567,P＜0.001)。Spearman相关性分析可得:HPV16病毒载量与宫颈组织病变程度之间呈正相关（r=0.229,P＜0.001）,AIM2表达水平与HPV16病毒载量也呈正相关（r=0.467,P＜0.001）。结论:宫颈病变程度与AIM2蛋白表达水平及HPV16病毒载量密切相关,AIM2蛋白表达水平及HPV16病毒载量随病变程度增加而增加。     

The significance of the Papanicolaou smear diagnosis of low-grade squamous intraepithelial lesion cannot exclude high-grade squamous intraepithelial lesion

BACKGROUND: Cervical cytologic specimens that show a low-grade squamous intraepithelial lesion (LSIL) occasionally contain a few cells that are suspicious for, but not diagnostic of, a high-grade squamous intraepithelial lesion (HSIL). In such cases, a diagnosis of LSIL cannot exclude HSIL is rendered. The objective of the current study was to assess the positive predictive value (PPV) for HSIL in follow-up cervical biopsies for these cases. METHODS: One hundred forty-four women with a Papanicolaou (Pap) diagnosis of LSIL cannot exclude HSIL and their follow-up cervical biopsies were reviewed. Results were compared with a control group of 155 women with a Pap diagnosis of LSIL. A subset of biopsies was tested and typed for human papillomavirus (HPV) DNA by polymerase chain reaction amplification using consensus primers followed by restriction fragment length polymorphism analysis. HPVs were scored as low-risk or high-risk types. RESULTS: Women with LSIL cannot exclude HSIL had a higher incidence of HSIL (PPV = 29%) on follow-up cervical biopsy than the control group (PPV = 15%, P < 0.01). In addition, SIL, indeterminate grade was diagnosed in 10% of cervical biopsies in the study group as compared with 4% in controls. Review of Pap smears from the study group showed that there were 3 types of cells suspicious for a high-grade lesion: atypical squamous metaplastic cells (62%), atypical keratinized cells (20%), and dysplastic cells of borderline nuclear-to-cytoplasm ratio (18%). HPV analysis confirmed the presence of high-risk HPV types in the study cases with high-grade cervical biopsies. CONCLUSIONS: Women with a Pap diagnosis of LSIL cannot exclude HSIL appear to be more likely to harbor a high-grade lesion than those diagnosed with LSIL alone. Its use appears warranted. Women with this diagnosis merit appropriate clinical follow-up to exclude HSIL.     

直肠癌组织PI3K和Survivin及VEGF表达与肿瘤侵袭转移相关性的探讨

目的:探讨磷脂酰肌醇3-激酶(PI3K)、存活素(Survivin)及血管内皮生长因子(VEGF)蛋白在人直肠癌组织中的表达,及其与直肠癌临床分期、组织学分级和侵袭转移的相关性及意义.方法:免疫组化SP法检测PI3K、Survivin和VEGF蛋白在60例直肠癌、30例直肠腺瘤及10例正常直肠组织中的表达.结果:PI3K在直肠癌、腺瘤和正常组织中的异常表达率分别为81.7％(49/60)、36.7％(11/30)和30.0％(3/10),差异有统计学意义,x2=17.86,P=0.001;Survivin的阳性表达率分别为90.0％(54/60)、80.0％(24/30)和20.0％(2/10),差异有统计学意义,x2=9.54,P=0.002;VEGF的异常表达率分别为71.7％(43/60)、43.3％(13/30)和30.0％(3/10),差异有统计学意义,x2=5.68,P=0.025.PI3K、Survivin及VEGF的异常表达均与临床分期及转移密切相关,P值均＜0.05.VEGF在直肠癌组织中染色阳性者(11.04±1.68)微血管密度(MVD)较染色阴性者(7.66±1.22)高,t=7.53,P＜0.05.在直肠癌组织中PI3K与Survivin(r=0.396,P=0.001)和VEGF (r=0.417,P=0.000 5)表达呈正相关,Survivin与VEGF表达呈正相关,r=0.332,P=0.005.PI3K和Survivin及VEGF蛋白协同阳性表达的侵袭转移率为55.0％(33/60),其中Ⅳ期远处转移率为93.8％(15/16).结论:PI3K和Survivin及VEGF蛋白的表达与临床分期及肿瘤侵袭转移密切相关,提示PI3K和Survivin及VEGF信号转导通路在人直肠癌侵袭转移中起重要作用.     

宫颈液基细胞学筛查阴性及高危型人乳头瘤病毒筛查阳性患者临床病理特征分析

目的:分析宫颈液基细胞学(liquid-based thinlayer cytologic test,TCT)筛查阴性、高危型人乳头瘤病毒(high risk-human papillomavirus,HR-HPV)筛查阳性患者临床病理特征,探讨TCT阴性、HR-HPV阳性患者行宫颈病理活检的时机和意义。方法:选取2020年01月至2021年03月期间我院收治的TCT阴性且HR-HPV16和(或)18阳性或间隔1年后TCT阴性且15种HR-HPV的1种或多种持续阳性患者1 141例作为研究对象,进一步行电子阴道镜活检,分析TCT阴性、HR-HPV阳性状态下HPV分型及宫颈病变的临床病理和流行病学特征。结果:单一型HPV感染870例(76.2%),多重感染271例(23.8%);检出率最高的前5位HR-HPV亚型依次为HPV16、52、58、51、39。有491例接受阴道镜下组织活检,活检率43.0%(491/1 141),共检出LSIL 71例(14.5%)、HSIL 66例(13.4%)、宫颈癌6例(1.2%)。40岁以下年轻女性HSIL及以上病变的发生率更高,而在60岁及以上女性再次出现发病高峰,差异有统计学意义(χ2=9.950,P=0.041)。HPV16和(或)18亚型感染女性的活检率高于其余15种HR-HPV感染者(χ2=4.207,P=0.040),HPV16和(或)18感染女性的HSIL及宫颈癌的比率均高于其余15种HR-HPV感染者,差异有统计学意义(χ2=11.831,P=0.001; χ2=6.962,P=0.008)。多重感染女性的宫颈癌的比率高于单一感染者,差异有统计学意义(χ2=5.956,P=0.015);而其他宫颈组织病变程度(正常或宫颈炎、LSIL、HSIL)与HPV病毒感染种类数无显著相关(P均＞0.05)。结论:TCT检查存在较高的假阴性率,对于HPV16和(或)18感染患者首诊即应行阴道镜检查,而对于未行活检患者应重点加强随访管理。