Stromal cells play a role in cervical cancer progression mediated by MMP-2 protein

Metalloproteinases, especially metalloproteinase-2 (MMP-2), are known for their role in the degradation of the extracellular matrix. Nevertheless, a thorough understanding of MMP-2 expression in neoplastic lesions of the uterine cervix has yet to be accomplished. This study aimed to analyze the MMP-2 expression in cervical intraepithelial neoplasia III (CIN3) and in cervical squamous cell carcinoma, in tumor cells and adjacent stromal cells. MMP-2 expression was assessed by an immunohistochemical technique. MMP-2 expression was greater in the stromal cells of invasive carcinomas than in CIN3 (p < 0.0001). MMP-2 expression in stromal cells correlates with the clinical stage, gradually increasing as the tumor progresses (p = 0.04). This study corroborates that stromal cells play an important role in tumor invasion and progression, mediated by the progressive enhancement of MMP-2 expression from CIN3 to advanced invasive tumor. The intense MMP-2 expression most probably is associated with poor tumor prognosis.     

Expression of matrix metalloproteinase-2 in preinvasive and invasive carcinoma of the uterine cervix

PURPOSE: To study the immunohistochemical expression of matrix metalloproteinase-2 (MMP-2) in preinvasive and invasive carcinoma of the uterine cervix so as to demonstrate whether the expression of MMP-2 is an early or late event in the process of dedifferentiation and cancer progression. METHODS: A total number of 50 samples of cervical tissue were studied for MMP-2 immunoreactivity. The cases were selected to include ten normal cases used as a control group, 20 CIN cases and 20 cervical carcinoma cases. The CIN group was subdivided into CIN1 (n = 7), CIN2 (n = 6) and CIN3 (n = 7), while the carcinoma group was represented by squamous cell carcinoma (n = 16) and adenocarcinoma (n = 4). RESULTS: MMP-2 expression was totally absent in control cervices and low-grade squamous intraepithelial lesions, while high-grade squamous intraepithelial neoplasia and invasive carcinoma showed up-regulation of MMP-2 expression with no significant difference concerning the type of carcinoma. This overexpression of MMP-2 points to the possibility that it is an early marker of tumor progression in cervical carcinoma. CONCLUSIONS: MMP-2 has a key role in extracellular matrix degradation and invasion in carcinoma of the uterine cervix. Its expression in high-grade squamous intraepithelial lesions may denote a potential risk for invasion and metastasis.     

Detection of human papillomavirus DNA in human cervical lesions by tissue in situ nucleic acid hybridization

Cervical cancer is one of the most common female cancers in Taiwan. Certain types of human papillomavirus (HPV) are frequently detected in the epithelial precancerous and cancerous lesions of the cervix. By the use of tissue in situ hybridization, we investigated the relationship of various types of HPV (group I, HPV-6 & 11, group II, HPV-16 & 18, group III, HPV-31, 33 & 35) with cervical condyloma, carcinoma as well as precancerous lesions. Group I HPV DNAs were mainly found in cervical condylomatous lesions (2/2) of the cervix and cervical intraepithelial neoplasia I (CIN I) (2/4), but were only occasionally found in CIN II (1/4), CIN III (1/9) or non-keratinized squamous cell carcinoma (1/15). HPV DNAs of groups II and III were mainly detected in lesions of CIN III (5/9) and invasive squamous cell carcinoma (large cell, keratinized type: 4/7; large cell, non-keratinized type: 11/15). HPV DNA sequences were invariably detectable only in the cell nuclei of condyloma or dysplastic epithelium or invasive carcinoma. However, they could not only be detected in the upper layer dysplastic cells and koilocytes but also in the well and poorly differentiated cervical cancer cells. The distribution of HPV DNA positive cells in the carcinomas fell into four different patterns: (1) upper zone and non-invasive regions of the carcinoma (11/22, 50%), (2) basal zone and invasive regions (2/22, 9%), (3) randomly scattered (7/22, 32%), and (4) extensively distributed over the whole tumor lesions (2/22, 9%). Thus, our results are consistent with a strong correlation between the presence of HPV-16, 18, 31, 33 and 35 and malignant conversion of cervical epithelial cells.     

Comparative study of MMP-2 (matrix metalloproteinase 2) immune expression in normal uterine cervix, intraepithelial neoplasias, and squamous cells cervical carcinoma

OBJECTIVE: This study was undertaken to evaluate the levels of matrix metalloproteinase 2 (MMP-2) in the precursors lesions and in the invasive cervical carcinoma and to quantify the immune reactive expression of MMP-2, using MMP-2 immunohistochemistry, in intraepithelial cervical neoplasias and in the invading cervical carcinoma. STUDY DESIGN: We evaluated 60 samples of cervical tissues using immunohistochemistry for MMP-2 in 5 distinct groups. The groups were divided in control, cervical intraepithelial neoplasia I (CIN I), CIN II, CIN III, and cervical invading carcinoma. RESULTS: MMP-2 expression was found gradually increased according to the degree of cervical intraepithelial neoplasia and cervical carcinoma. (Control相似文献   

宫颈癌前病变与宫颈鳞癌组织中Foxp3的表达及临床意义

目的 观察宫颈鳞癌及癌前病变组织中Foxp3的表达情况.方法 采用免疫组化检测浸润性宫颈鳞癌(FIGOⅠ期或ⅡA期,共20例)、宫颈上皮内瘤样病变(CIN1、CIN2、CIN3各20例)、宫颈HPV感染(20例)及正常宫颈(20例)组织中Foxp3的表达情况.结果 浸润性宫颈鳞癌与CIN3患者宫颈组织中Foxp3表达明...     

Different T-cell receptor (TCR) zeta chain expression in cervical cancer and its precursor lesions

OBJECTIVE: Cervical cancer is associated with infection of epithelial cells with the human papillomavirus (HPV) type 16 and HPV18. A functional signalling machinery in T-cells is required in order to successfully fight and eradicate HPV16+ transformed epithelial cells. One of the key signalling molecules associated with the T-cell receptor (TCR) is the homodimeric zeta chain molecule. MATERIAL AND METHODS: 28 formalin fixed und paraffin embedded samples of cervical tissue with cervical intraepithelial lesions CIN I (n = 3), CIN III (n = 7), invasive cervical carcinoma (CC) (n = 13) and normal cervical tissue (n = 5) has been evaluated for HPV-PCR und zeta chain immunohistochemistry. For immunohistochemistry a monoclonal IgG1 anti TZR zeta chain-antibody (mAb) has been used (clone 6B 10.2, Santa Cruz, Heidelberg, Germany). According to the performed Western-Blot analysis on peripheral blood monocytes (PBMCs) the used mAb has specifically recognized TCR zeta chains. RESULTS: We show reduced protein zeta chain expression associated with invasive cervical cancer, but not with pre-invasive HPV16-positive lesions or HPV16-negative normal cervix tissue. CONCLUSIONS: Thus, reduced TCR zeta chain expression is not necessarily linked to a chronic viral infection, nor to the presence of transformed cells, but rather to the stromal invasion of the cancer lesion.     

Detection of HPV DNA in the uterine cervical lesions by polymerase chain reaction and in situ hybridization]

Human papillomavirus (HPV) is found in close association with carcinogenesis of the uterine cervix. We applied a new in vitro gene amplification technology, the polymerase chain reaction (PCR) to detect HPV 16 and 18 in cervical exfoliated cells. HPV infections were detected in 5 (16%) of 31 women with no pathological lesions of the uterine cervix (normal), 16 (24%) of 67 with cervical intraepithelial neoplasia (CIN) and 6 (38%) of 16 with invasive cervical cancer. Moreover, 10% formalin-fixed and paraffin-embedded tissue sections were prepared from the uterine cervix of these 27 women with PCR-proven HPV infection and were examined for the histological localization of HPV-DNA by in situ hybridization with biotin-labeled DNA probes of HPV types 6/11, 16/18 and 31/33/35. HPV-DNA type 16/18 was detected in 3 of 5 normal women, 2 of 4 CINs I, 2 of 3 CINs II, 6 of 9 CINs III and 6 of 6 invasive cervical cancers. HPV-DNA type 6/11 was detected in 6 of 6 condylomas. Viral DNA sequence was detected in the superficial cells of CIN I and II, and it was distributed through entire thickness layer of undifferentiated cells derived from CIN III and squamous cell carcinoma. In addition, the staining intensity became weak as the lesion progressed. These differences between lesions might be due to the difference in the viral form in the nuclei, ie whether an episomal or integrated form. Thus, an in situ hybridization technique with a biotin-labeled DNA probe as well as the PCR method is useful for the detection of HPV in clinical samples.     

子宫颈鳞状细胞癌细胞外间质胶原重构及其调控机制的研究

目的 :检测Ⅰ、Ⅲ和Ⅳ型胶原及相关的调控间质金属蛋白酶 (MMPs)蛋白的表达 ,探讨子宫颈鳞状细胞癌细胞外间质 (ECM)重构与癌细胞侵袭性生长的关系及调控机制。方法 :应用免疫荧光染色技术及激光共聚焦显微镜观察检测 ,正常子宫颈及不同分化程度的子宫颈鳞状细胞癌石蜡包埋组织切片的Ⅰ、Ⅲ和Ⅳ型胶原及MMP - 1、MMP - 2、TIMP - 2、MT1-MMP蛋白表达。结果 :正常子宫颈组织中 ,细胞外间质内可见结构致密的Ⅰ、Ⅲ型胶原的表达 ,Ⅳ型胶原蛋白呈线状定位于基底膜内 ;MMP - 1、MMP - 2、MT1-MMP、TIMP - 2蛋白表达不明显 ,只有少数鳞状上皮中下层细胞、间质细胞及血管壁细胞膜和细胞浆内见较弱荧光。子宫颈鳞状细胞癌组织中 ,3型胶原均明显降解 ,表现为Ⅰ、Ⅲ型胶原结构稀疏 ,排列紊乱 ,癌细胞团周围基底膜内的Ⅳ型胶原的线状荧光减弱、断裂甚至缺失 ,以低分化鳞状细胞癌明显 ;4种金属蛋白酶染色明显增强 ,癌细胞浆内可见不同程度的阳性染色 :细胞分化程度越低 ,MMP - 1、MMP - 2、MT1-MMP染色越强 ,而TIMP- 2蛋白的染色结果相反。结论 :子宫颈鳞状细胞癌时 ,ECM重构 ,表现为Ⅰ、Ⅲ、Ⅳ型胶原降解 ,其程度与癌细胞分化程度呈负相关。间质金属蛋白酶MMP - 1、MMP - 2、MT1-MMP和TIMP - 2在ECM重构中起一定的?     

基质金属蛋白酶-9及基质金属蛋白酶组织抑制物-1表达失衡与宫颈癌局部肿瘤血管生成的关系

目的 :探讨基质金属蛋白酶 - 9(MMP 9)和基质金属蛋白酶组织抑制物 - 1(TIMP 1)在宫颈癌局部肿瘤血管生成中的作用。方法 :采用免疫组织化学SP法检测 75例早期宫颈癌 (ICC)、18例宫颈上皮内瘤样病变 (CIN)和 15例癌旁正常宫颈上皮 (NCE)中MMP 9和TIMP 1的表达情况 ,并检测其中微血管密度 (MVD ,CD3 4 标记 )。结果 :从NCE组到CIN组再到ICC组 ,MMP 9的阳性表达率显著升高 (P <0 0 5 )而TIMP 1未见升高 (P >0 0 5 ) ,并且TIMP 1在ICC组的阳性表达率显著低于MMP 9(P <0 0 1)。MMP 9在ICC组中表达与MVD显著正相关 (r =0 2 87,P <0 0 5 ) ,而TIMP 1与MVD无显著相关性 (r=0 195 ,P >0 0 5 )。宫颈癌中MMP 9表达高于TIMP 1者 ,其MVD显著高于MMP 9表达低于TIMP 1者 (P <0 0 5 )。结论 :MMP 9和TIMP 1表达失衡可能在宫颈癌局部肿瘤血管生成中起重要作用 ,MMP 9表达增强而TIMP 1表达降低 ,其血管生成能力可能显著增强 ,但并非唯一决定因素。检测宫颈癌中MMP 9和TIMP 1表达对进一步了解宫颈癌局部血管生成情况有一定的应用价值。     

Type IV collagen in the basal membrane of human papillomavirus associated premalignant and malignant squamous cell lesions of the uterine cervix

In the present study, the expression of type IV collagen associated with the basal membrane (BM) was studied histochemically (indirect immunoperoxidase-antiperoxidase) in cervical human papillomavirus (HPV) lesions (diagnosed using in situ DNA hybridization) of different grades. The expression of type IV collagen in premalignant epithelial lesions (HPV with and without cervical intraepithelial neoplasia) was identical with that in the BM of normal exocervical epithelium, in contrast to 60% (3/5) of carcinoma in situ lesions and 90% (10/11) of invasive carcinomas, where the staining pattern was interrupted and the staining intensity reduced. Thus, the expression of type IV collagen seems to remain unchanged during the entire spectrum of premalignant stages of cervical HPV lesions. This suggests that the squamous epithelial cells responsible for the formation of the BM are not affected by this virus at early stages of the disease, and immunohistochemical recognition of an intact staining pattern of type IV collagen may signify well-preserved basal cell function (confined to nonmalignant?) HPV-infected squamous epithelium.     

E-cadherin expression during progression of squamous intraepithelial lesions in the uterine cervix

Alterations of E-cadherin expression in cervical intraepithelial neoplasias and invasive carcinomas of the uterine cervix have been described by some authors but their clinical significance has not yet been clarified. Archival specimens of 27 normal cervical epithelia, 15 atypical cells of undetermined origin (ASCUS), 53 low-grade squamous intraepithelial lesions (LSIL), 19 high-grade squamous intraepithelial lesions (HSIL) and six invasive squamous carcinomas were evaluated for E-cadherin expression. The cytological material was processed using liquid based cytology (ThinPrep technique) and immunostained for E-cadherin. All HPV infections (koilocytes) showed strong cell membranous E-cadherin expression. In HSIL a strong decrease in E-cadherin expression and heterogeneous distribution was noticed. In the relatively small number of squamous cell carcinomas of the cervix studied, a significant decrease or loss in E-cadherin expression, predominantly cytoplasmic, was noted. We concluded that decreased E-cadherin expression appears to be a useful parameter of malignant potential of cervical lesions. E-cadherin immunoexpression could provide an additional criterion in correlation with cyto- and histomorphology and colposcopy to define high grade CIN lesions.     

MMP-2 and TIMP-2 expression correlates with poor prognosis in cervical carcinoma--a clinicopathologic study using immunohistochemistry and mRNA in situ hybridization.

OBJECTIVE: The spread of malignant neoplasms is closely associated with matrix and basement membrane degradation, mediated by various classes of proteolytic enzymes. Matrix metalloproteinases (MMP) appear to have a key role in the sequence of events that lead to local invasion and metastasis. The present study evaluated the role of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinases-2 (TIMP-2), and membrane-type metalloproteinase (MT1-MMP) in cervical neoplasia. METHODS: We have analyzed 49 uterine cervical squamous cell carcinomas, 10 cases of high-grade cervical intraepithelial neoplasia (CIN II-III), and 10 control cervices for the presence of MMP-2, TIMP-2, and MT1-MMP using in situ hybridization. MMP-2 protein expression was evaluated using immunohistochemistry. Results were analyzed for possible correlation with disease outcome. RESULTS: MMP-2, TIMP-2, and MT1-MMP mRNA were localized to both stromal and tumor cells. However, an intense signal for MMP-2 was detected almost exclusively in tumor cells and was uniformly absent from CIN lesions and control cervices. Conversely, intense signals for TIMP-2 and MT1-MMP were detected in both stromal and tumor cells of invasive carcinomas, more often for the former. As with MMP-2, they were absent from CIN lesions. MMP-2 protein expression was enhanced in tumor cells compared to CIN cases and controls, significantly compared to the latter (P = 0.01). The presence of both MMP-2 and TIMP-2 mRNA in tumor cells correlated with advanced stage (P = 0.003 for MMP-2, P = 0.002 for TIMP-2) and with poor survival (P = 0.003 for MMP-2, P = 0.002 for TIMP-2) in univariate analysis. In addition, their presence in tumor cells intercorrelated (P = 0.002). In multivariate survival analysis, MMP-2 presence retained its association with survival (P = 0.004), in addition to patient age (P = 0.027) and advanced stage (P = 0. 0002). CONCLUSIONS: Both MMP-2 and TIMP-2 have a key role in extracellular matrix invasion in cervical carcinoma, largely through their elaboration by tumor cells. The presence of mRNA for both proteins is interrelated and is associated with poor survival.     

Human papillomavirus messenger RNA expression in adenocarcinoma in situ of the uterine cervix

Over recent years, the association between human papillomavirus (HPV) and squamous cell carcinoma of the cervix and its precursors has been well established, largely as a result of advances in the techniques of molecular biology. A similar association between HPV and invasive adenocarcinoma of the cervix has also been recently demonstrated; however, little work has been published on the relationship between the precursor lesion, adenocarcinoma in situ (ACIS), and HPV. We have therefore undertaken an in situ hybridization study of 22 cases of known cervical ACIS using probes for HPV messenger RNA expression. Seventeen of these had residual ACIS in the blocks studied, 15 of which (88.6%) expressed HPV messenger RNA. Five cases were positive for HPV 16 and 10 cases for HPV 18. Early invasive adenocarcinoma was present with ACIS in three cases and one case had early invasion plus cervical intraepithelial neoplasia (CIN III). These invasive lesions showed a similar type and degree of HPV expression as the in situ component. One section had only residual CIN III, which was positive for HPV type 18. Four cases had only minor glandular atypias (less than ACIS) in the studied sections, and all four of these were negative for HPV expression. None of the normal endocervical epithelia in any of the sections were positive by this technique. In summary, the finding of HPV messenger RNA expression in nearly 90% of cervical ACIS supports a possible role for these viruses in the pathogenesis of glandular neoplasms of the uterine cervix.     

组蛋白H3乙酰化和HPV感染的相关性及其对CINⅠ转归的影响

目的:探讨组蛋白H3乙酰化状态与宫颈HPV感染的相关性,及其分别与CINⅠ级转归的关系。方法:(1)选择2006年1月～2008年1月我院治疗的正常宫颈、CINⅠ、CINⅡ～Ⅲ、宫颈癌组织各30例,用免疫组化技术检测其组蛋白H3乙酰化表达水平;(2)对2006年1月～2008年1月仁济医院阴道镜下活检确诊为CINⅠ级的161例患者,用免疫组化技术检测组织中组蛋白H3乙酰化表达的水平,采用凯普技术检测宫颈HPV感染分型。结果:(1)CIN病变组组蛋白H3乙酰化水平与正常宫颈组和宫颈癌组的差异有统计学意义(P0.01)。CINⅠ和CINⅡ～Ⅲ组差异有统计学意义(P0.05);(2)组蛋白H3乙酰化表达水平增加,进展为CINⅡ级以上的发生率进行性升高,(+++)组最高达80%,差异有统计学意义(P0.05);(3)宫颈高危型HPV16/18感染的CINⅠ级,其组蛋白H3乙酰化表达水平明显高于低危型和非16/18高危型(P0.05);进展为CINⅡ级以上发生率与低危型和非16/18高危型的差异有统计学意义(P0.05);(4)不同的治疗方案对CINI级转归的影响不同,LEEP术后随访6月无1例复发,HPV转阴率77.94%(P0.05)。结论:组蛋白H3乙酰化水平和HPV感染类型与CINI级转归密切相关。     

Expression of matrix metalloproteinase-9 in squamous cell carcinoma of the uterine cervix-clinicopathologic study using immunohistochemistry and mRNA in situ hybridization

OBJECTIVE: Invasion of the extracellular matrix and blood vessels by malignant neoplasms, with subsequent distant dissemination, is a key event in tumor progression. This process appears to be mediated largely through the action of matrix metalloproteinases (MMPs), a family of proteolytic enzymes produced by both stromal and tumor cells. The role of gelatinases (MMP-2 and MMP-9) in basement membrane and matrix degradation was described in various tumors. We studied MMP-9 protein expression in cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma using immunohistochemistry and detected MMP-9 mRNA using in situ hybridization. METHODS: Fifty squamous cell carcinomas, 10 cases of CIN II-III, and 10 normal cervices were stained for MMP-9, using a monoclonal antibody. The presence of MMP-9 mRNA was studied using in situ hybridization. Results were correlated with patient survival during a follow-up period of up to 167 months (average, 41 months). RESULTS: Immunohistochemical staining of tumor cells for MMP-9 was noted in 36/50 (72%) carcinomas and 5/10 (50%) CIN lesions, but was uniformly absent from the nonneoplastic epithelium adjacent to tumors and from control cervices. Peritumoral staining of stromal cells was observed in 27/50 (54%) carcinomas, but only in 3/10 (30%) CIN lesions and 1/10 (10%) control cervices. The presence of MMP-9 mRNA was detected in tumor cells in 39 (78%) carcinomas and 8 (80%) CIN lesions, but only in 4 (40%) control cervices. An intense signal for MMP-9 mRNA was observed most frequently in carcinomas. MMP-9 mRNA was detected in stromal cells in the majority of cases. However, an intense signal was observed only in stromal cells around invasive tumors. In survival analysis, age (P = 0.016), grade (P = 0. 016), and stage (P = 0.001) showed independent correlation with poor survival. Neither MMP-9 protein expression nor an intense signal for MMP-9 mRNA was associated with poor survival, although the latter was observed more frequently in neoplastic cells of lethal tumors (8/14 tumors vs 11/36 nonlethal tumors). CONCLUSIONS: MMP-9 mRNA and protein expression are elevated in tumor and stromal cells of both high-grade CIN and invasive squamous cell carcinoma of the uterine cervix. Thus, MMP-9 is possibly an early marker of tumor progression in squamous lesions of the cervix. An intense stromal signal for MMP-9 mRNA characterizes some invasive carcinomas. Expression of MMP-9 in cervical carcinoma cells is present in both lethal and nonlethal tumors, consistent with the key role of this proteolytic enzyme in invasion, and does not appear to predict disease outcome.     

In situ hybridization analysis of human papillomavirus DNA segregation patterns in lesions of the female genital tract

Various histologic features may be used to divide human papillomavirus (HPV)-related lesions of the genital tract into two groups: condylomata and "low-grade" or grade 1 cervical intraepithelial neoplasias (CIN 1) versus "high-grade" or grade 2 and 3 intraepithelial neoplasias. Using in situ hybridization analysis we correlated HPV DNA type with histologic features in 350 biopsies of lesions from the cervix, vulva, and perianal region. HPV DNA was most commonly found in vulvar and perianal condylomata (39/46, 85%), whereas the rate in CIN 1 lesions was 72% (86/120). The rates were 53% (40/76) and 57% (12/21) in CIN 2/3 and vulvar intraepithelial neoplasm (VIN) grades 2 and 3, respectively. The HPV type in all but 2 of the 39 perianal and vulvar condylomata which contained HPV was 6/11. Despite their similar histologic features, the HPV type in only 23 of 86 (27%) CIN 1 cases with detectable HPV was 6/11 compared to 31 of 86 (36%) which contained HPV 16-related DNA and 32 of 86 (37%) which contained HPV 31,-33, or -35-related DNA. The viral DNA in the majority of CIN 2/3 lesions and all of the VIN 2/3 lesions was HPV-16 related; no CIN 2/3 or VIN 2/3 lesion had HPV 6/11-related DNA. It is concluded that although cutaneous genital tract condylomata are highly associated with HPVs of low oncogenic potential (types 6 and 11), these HPV types are not as frequent as the oncogenic HPVs (16, 31, 33, and 35) in CIN 1 lesions. Further, HPV 6/11 appears to be very rarely associated with CIN 2/3 or VIN 2/3 lesions.     

Human papillomavirus DNA in adenocarcinoma in situ, microinvasive adenocarcinoma of the uterine cervix, and coexisting cervical squamous intraepithelial neoplasia

Previously, human papillomavirus (HPV) DNA, mainly HPV-18 DNA, was detected in more than 40% (17/40 cases) of invasive adenocarcinoma of the uterine cervix in our laboratory. In order to identify HPV DNA in the precursor lesions of adenocarcinoma of the cervix, 11 cases of adenocarcinoma in situ containing microinvasive adenocarcinoma and 10 cases of adenocarcinoma in situ were studied for the presence of HPV DNA by in situ hybridization using highly sensitive 3H-labeled HPV-16 and HPV-18 DNA probes. HPV types present in cervical squamous intraepithelial neoplasia (CIN) coexisting with adenocarcinoma in situ and microinvasive adenocarcinoma were also studied. Apart from the coexisting CIN II-III with glandular neoplasms, 48 cases of CIN III (severe dysplasia and squamous carcinoma in situ) removed by conization or hysterectomy and known to be free of adenocarcinoma were used for comparison. HPV DNA was detected in 64% of microinvasive adenocarcinoma, 70% of adenocarcinoma in situ, and 63% of the control CIN III. HPV-18 DNA was the preponderant type of HPV DNA found in adenocarcinoma in situ and microinvasive adenocarcinoma. All cases of HPV DNA-positive microinvasive adenocarcinoma contained the same type of HPV DNA as the lesions of coexisting adenocarcinoma in situ. CIN coexisting with microinvasive adenocarcinoma or adenocarcinoma in situ contained the same type of HPV as identified in the glandular lesions, whereas all of the HPV DNA-positive control CIN III cases contained HPV-16 DNA. These results suggest that adenocarcinoma in situ is a precursor lesion of adenocarcinoma of the cervix that contains HPV DNA, and that CIN coexisting with adenocarcinoma may be a result of a metaplastic process of adenocarcinoma or of bidirectional differentiation of the affected reserve cells.     

Synchronous Ovarian and Cervical Squamous Intraepithelial Neoplasia: An Analysis of HPV Status

In contrast to the strong association between human papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN), the relationship between HPV and squamous epithelial lesions of the ovary is less clear. We report a case of synchronous ovarian and cervical squamous intraepithelial neoplasia. To investigate the possible association between HPV and squamous intraepithelial neoplasia/carcinomain situ(CIS) of the ovary, DNA was extracted from paraffin-embedded tissues including normal cervix, CIN, CIS from both ovaries, and an area of ovarian endometriosis. All samples were positive for HPV 16 E6 except for one of the two samples from the normal cervical squamous epithelium. These results support the hypothesis that HPV may be involved in the development of ovarian squamous intraepithelial neoplasia.     

半乳糖凝集素-1蛋白在宫颈病变组织中的表达及其与高危型人乳头瘤病毒的关系

目的:探讨半乳糖凝集素-1(Galectin-1)蛋白在宫颈上皮内瘤变(CIN)及宫颈癌中的表达及其与高危型人乳头瘤病毒(HR-HPV)的关系。方法:用免疫组织化学法检测宫颈癌(54例)、CINⅠ(10例)、CINⅡ(20例)、CINⅢ(25例)和正常宫颈组织(20例)中Galectin-1蛋白的表达,用第二代杂交捕获法(HC-Ⅱ)检测HR-HPV感染情况,分析Galectin-1与CIN及HR-HPV的关系。结果:Galectin-1蛋白在正常宫颈、CINⅠ、CINⅡ、CINⅢ和宫颈癌组织中的阳性表达率分别为5.0%、20.0%、40.0%、56.0%、48.1%,随着CIN病变程度的加重,Galectin-1蛋白阳性表达逐渐增强;宫颈癌和CINⅡ、CINⅢ的Galectin-1蛋白阳性表达率明显高于正常宫颈组织和CINⅠ(P<0.01),宫颈癌与CINⅡ、CINⅢ间比较、差异无统计学意义(P>0.05)。宫颈癌中Galectin-1蛋白阳性表达在有否淋巴结转移、组织学分级、临床分期和有否HR-HPV的感染中比较,差异有统计学意义(P<0.05,P<0.01),在不同组织学类型中比较,差异无统计学意义(P>0.05)。结论:Galectin-1蛋白表达增强与宫颈病变的进展有一定关系,HR-HPV可能通过诱导宫颈上皮高表达Galectin-1而促使宫颈癌发生、发展。