陳曉燕泰安市婦幼保健院病理科,山東泰安 271000
DLC-1和cyclinD1在宮頸鱗狀細(xì)胞癌中的表達(dá)及意義
陳曉燕
泰安市婦幼保健院病理科,山東泰安 271000
目的 探討DLC-1和cyclinD1在宮頸鱗狀細(xì)胞癌中的表達(dá)。方法 整群選擇2005年1月—2013年12月該院收治的62例宮頸鱗狀細(xì)胞癌標(biāo)本、38例宮頸上皮內(nèi)瘤變標(biāo)本、26例正常宮頸組織標(biāo)本,以免疫組化SP法檢測(cè)3組標(biāo)本中DLC-1 和cyclinD1的表達(dá)。結(jié)果 DLC-1在宮頸鱗狀細(xì)胞癌、宮頸上皮內(nèi)瘤變、正常宮頸組織中的陽(yáng)性表達(dá)率分別為27.4%、76.3%、92.3%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);高、中、低病理分級(jí)DLC-1陽(yáng)性表達(dá)率分別為42.9%、27.9%、16.7%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);Ⅰ~Ⅱa期DLC-1陽(yáng)性表達(dá)率為41.4%,明顯高于Ⅱb~Ⅳ期的15.2%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);無(wú)淋巴結(jié)轉(zhuǎn)移DLC-1陽(yáng)性表達(dá)率為34.9%,明顯高于有淋巴結(jié)轉(zhuǎn)移的10.5%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。cyclinD1在宮頸鱗狀細(xì)胞癌、宮頸上皮內(nèi)瘤變、正常宮頸組織中的陽(yáng)性表達(dá)率分別為66.1%、5.3%、0%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);高、中、低病理分級(jí)cyclinD1陽(yáng)性表達(dá)率分別為42.9%、67.4%、75.0%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);Ⅰ~Ⅱa期cyclinD1陽(yáng)性表達(dá)率為48.3%,明顯低于Ⅱb~Ⅳ期的81.8%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);無(wú)淋巴結(jié)轉(zhuǎn)移cyclinD1陽(yáng)性表達(dá)率為58.1%,明顯低于有淋巴結(jié)轉(zhuǎn)移的84.2%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。DLC-1與cyclinD1在宮頸鱗狀細(xì)胞癌中的表達(dá)呈負(fù)相關(guān)性(r=-0.519,P<0.05)。結(jié)論DLC-1在宮頸鱗狀細(xì)胞癌的陽(yáng)性表達(dá)較低,而cyclinD1在宮頸鱗狀細(xì)胞癌的陽(yáng)性表達(dá)較高,兩者均與宮頸鱗狀細(xì)胞癌發(fā)展、侵襲、轉(zhuǎn)移等密切相關(guān)。
宮頸鱗狀細(xì)胞癌;DLC-1;cyclinD1
宮頸癌是婦女臨床常見性惡性腫瘤,其發(fā)病率僅低于乳腺癌,而其中又以鱗狀細(xì)胞癌的發(fā)病率最高,約70%[1]。當(dāng)前,鱗狀細(xì)胞癌的發(fā)病率逐年增加,且早期臨床無(wú)明顯癥狀,常在體檢中發(fā)現(xiàn)。病理學(xué)研究顯示,宮頸癌的發(fā)病過程復(fù)雜,涉及癌基因改變和細(xì)胞生長(zhǎng)的變化[2]。DLC-1為抑癌基因,在多數(shù)正常組織中的表達(dá)較高,在多數(shù)腫瘤中的表達(dá)較低[3]。cyclinD1是原癌基因,高表達(dá)可促進(jìn)細(xì)胞增殖[4]。當(dāng)前,DLC-1和cyclinD1在鱗狀細(xì)胞癌中表達(dá)的研究不多見,基于此,通過分析該院2005年1月—2013年12月間收治的62例宮頸鱗狀細(xì)胞癌標(biāo)本、38例宮頸上皮內(nèi)瘤變標(biāo)本、26例正常宮頸組織中DLC-1和cyclinD1的表達(dá)情況,探討了DLC-1和cyclinD1與鱗狀細(xì)胞癌發(fā)展、侵襲、轉(zhuǎn)移的關(guān)系,并對(duì)兩者的相關(guān)性進(jìn)行了分析。以期為宮頸癌的防治提供數(shù)據(jù)。現(xiàn)報(bào)道如下。
[作者簡(jiǎn)介]陳曉燕(1971-),女,山東泰安人,本科,主治醫(yī)師,研究方向:臨床病理診斷。
1.1 一般資料
62例宮頸鱗狀細(xì)胞癌標(biāo)本、38例宮頸上皮內(nèi)瘤變標(biāo)本、26例正常宮頸組織標(biāo)本均整群選自該院2005年1月—2013年12月病理科,且均經(jīng)病理證實(shí)。62例宮頸鱗狀細(xì)胞癌中,年齡35~ 76歲,平均(52.7±12.5)歲;高分化癌7例,中分化癌43例,低分化癌12例;FIGO分期:Ⅰ~Ⅱa期29例,Ⅱb~Ⅳ期33例;無(wú)淋巴結(jié)轉(zhuǎn)移者43例;有淋巴結(jié)轉(zhuǎn)移者19例?;颊咝g(shù)前均未進(jìn)行放療及化療的治療,且標(biāo)本經(jīng)病理醫(yī)師復(fù)檢。
1.2 方法
標(biāo)本經(jīng)10%中性福爾馬林固定,用石蠟包埋,做4 μm的切片。以SP法進(jìn)行免疫組化,操作依據(jù)試劑盒說明書進(jìn)行。并用乳腺癌作為陽(yáng)性對(duì)照,PBS組作為陰性對(duì)照。
1.3 結(jié)果判定
結(jié)果判定以雙評(píng)分法進(jìn)行[5],觀察DLC-1細(xì)胞質(zhì)和cyclinD1的細(xì)胞核,當(dāng)出現(xiàn)棕黃色顆粒、且染色的強(qiáng)度大于背景著色時(shí),判定為陽(yáng)性。細(xì)胞計(jì)分標(biāo)準(zhǔn):0分,陽(yáng)性細(xì)胞數(shù)<5%;1分,5%~25%;2分,26%~50%;3分,51%~75%;4分,>75%。顯色強(qiáng)度評(píng)分:0分,無(wú)著色;1分,淡黃色;2分,棕黃色;3分,棕褐色。兩評(píng)分乘積≤1,表示(-);1~3分,表示弱(+);>3,表示(+)。
1.4 統(tǒng)計(jì)方法
以SPSS 16.0進(jìn)行統(tǒng)計(jì)分析。計(jì)數(shù)資料用χ2檢驗(yàn)。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2.1 三組標(biāo)本中DLC-1和cyclinD1的表達(dá)
DLC-1在宮頸鱗狀細(xì)胞癌、宮頸上皮內(nèi)瘤變、正常宮頸組織中的陽(yáng)性表達(dá)逐漸增大,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);cyclinD1在宮頸鱗狀細(xì)胞癌、宮頸上皮內(nèi)瘤變、正常宮頸組織中的陽(yáng)性表達(dá)逐漸減小,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)果見表1。
2.2 DLC-1和cyclinD1與宮頸鱗狀細(xì)胞癌的關(guān)系
DLC-1和cyclinD1在宮頸鱗狀細(xì)胞癌中的陽(yáng)性表達(dá)與宮頸鱗狀細(xì)胞癌的分期、分級(jí)、淋巴轉(zhuǎn)移密切相關(guān),差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)果見表2。
表1 三組標(biāo)本中DLC-1和cyclinD1的表達(dá)[n(%)]
表2 DLC-1和cyclinD1與宮頸鱗狀細(xì)胞癌的關(guān)系[n(%)]
2.3 DLC-1與cyclinD1在宮頸鱗狀細(xì)胞癌中表達(dá)的相關(guān)性
DLC-1與cyclinD1在宮頸鱗狀細(xì)胞癌中表達(dá)的呈負(fù)相關(guān)性(r=-0.519)。結(jié)果見表3。
對(duì)于DLC-1在宮頸鱗狀細(xì)胞癌中的表達(dá),該組研究結(jié)果顯示:DLC-1在宮頸鱗狀細(xì)胞癌、宮頸上皮內(nèi)瘤變、正常宮頸組織中的陽(yáng)性表達(dá)率分別為27.4%、76.3%、92.3%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);高、中、低病理分級(jí)DLC-1陽(yáng)性表達(dá)率分別為42.9%、27.9%、16.7%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);Ⅰ~Ⅱa期DLC-1陽(yáng)性表達(dá)率為41.4%,明顯高于Ⅱb~Ⅳ期的15.2%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);無(wú)淋巴結(jié)轉(zhuǎn)移DLC-1陽(yáng)性表達(dá)率為34.9%,明顯高于有淋巴結(jié)轉(zhuǎn)移的10.5%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)果提示了:DLC-1在宮頸鱗狀細(xì)胞癌和宮頸上皮內(nèi)瘤變中的陽(yáng)性表達(dá)率顯著低于正常宮頸組織,并與宮頸鱗狀細(xì)胞癌的分化、分期、淋巴結(jié)轉(zhuǎn)移密切相關(guān)。早在1998年,張風(fēng)林等[5]在肝癌細(xì)胞系染色體的研究中首次發(fā)現(xiàn)了DLC-1,在基因組染色體中具有低表達(dá)。病理研究顯示,DLC-1在人體腦、心、肝、肺、乳腺等組織都有表達(dá),并可抑制肺癌、肝癌、前列腺癌等腫瘤細(xì)胞的生長(zhǎng),發(fā)揮抑癌作用。此外,Seng等[6]的研究發(fā)現(xiàn)宮頸癌會(huì)對(duì)DLC-1的啟動(dòng)子進(jìn)行甲基化修飾,造成DLC-1的失活,因此,DLC-1可以作為宮頸癌診治判斷的標(biāo)記物。宋明芮等[7]的研究結(jié)果表明,DLC-1的低表達(dá)參與了宮頸鱗狀細(xì)胞癌的發(fā)生、發(fā)展、侵襲、及轉(zhuǎn)移,本組結(jié)果與其結(jié)果一致。
表3 DLC-1與cyclinD1在宮頸鱗狀細(xì)胞癌中表達(dá)的相關(guān)性
對(duì)于cyclinD1在宮頸鱗狀細(xì)胞癌中的表達(dá),該組發(fā)現(xiàn):cyclinD1在宮頸鱗狀細(xì)胞癌、宮頸上皮內(nèi)瘤變、正常宮頸組織中的陽(yáng)性表達(dá)率分別為66.1%、5.3%、0%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);高、中、低病理分級(jí)cyclinD1陽(yáng)性表達(dá)率分別為42.9%、67.4%、75.0%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);Ⅰ~Ⅱa期cyclinD1陽(yáng)性表達(dá)率為48.3%,明顯低于Ⅱb~Ⅳ期的81.8%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);無(wú)淋巴結(jié)轉(zhuǎn)移cyclinD1陽(yáng)性表達(dá)率為58.1%,明顯低于有淋巴結(jié)轉(zhuǎn)移的84.2%,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)果提示了:CyclinD1在宮頸鱗狀細(xì)胞癌和宮頸上皮內(nèi)瘤變中的陽(yáng)性表達(dá)率顯著高于正常宮頸組織,并與宮頸鱗狀細(xì)胞癌的分化、分期、淋巴結(jié)轉(zhuǎn)移密切相關(guān)。CyclinD1是一種參與細(xì)胞周期精確調(diào)控的蛋白,維持細(xì)胞生長(zhǎng)發(fā)育的平衡。CyclinD1基因的變化可引起細(xì)胞周期的異常調(diào)控,進(jìn)而誘發(fā)細(xì)胞轉(zhuǎn)化、甚至癌變。病理研究顯示,CyclinD1可加速G1/S期的轉(zhuǎn)換,促進(jìn)細(xì)胞周期的進(jìn)程,當(dāng)CyclinD1的過度表,會(huì)造成細(xì)胞的持續(xù)性增殖,進(jìn)而形成腫瘤。此外,Shi等[8]的研究發(fā)現(xiàn)CyclinD1在宮頸癌組呈現(xiàn)高表達(dá),可作為早期宮頸癌診治的標(biāo)志物。王新華等[9]的研究顯示CyclinD1的高表達(dá)促進(jìn)了細(xì)胞周期進(jìn)程,引起細(xì)胞增殖的失控,促進(jìn)宮頸癌的發(fā)生,該組結(jié)果與其一致。
在DLC-1和cyclinD1的相關(guān)性分析中,發(fā)現(xiàn)DLC-1和cyclinD1在宮頸鱗狀細(xì)胞癌中的表達(dá)呈負(fù)相關(guān)性(r=-0.519,P<0.05)。結(jié)果提示了,DLC-1的低表達(dá)和cyclinD1的高表達(dá)在宮頸鱗狀細(xì)胞癌的發(fā)生、發(fā)展、侵襲中起重要作用。
綜上所述,DLC-1在宮頸鱗狀細(xì)胞癌的陽(yáng)性表達(dá)較低,而cyclinD1在宮頸鱗狀細(xì)胞癌的陽(yáng)性表達(dá)較高,兩者均與宮頸鱗狀細(xì)胞癌發(fā)展、侵襲、轉(zhuǎn)移等密切相關(guān)。
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Expression and Significance of DLC-1 and CyclinD1 in Cervical Squamous Cell Carcinoma
CHEN Xiao-yan
Pathology department,MCH of Tai'an city,Tai'an,ShandongProvince,271000 China
Objective To investigate the expression of DLC-1 and cyclinD1 in cervical squamous cell carcinoma.Methods 62 cases of cervical squamous cell carcinoma samples,38 cases of cervical intraepithelial neoplasia samples,26 cases of normal cervical tissue samples from January 2005 to December 2013 were selected,and the expression of DLC-1 and cyclinD1 were detected by immunohistochemistry SP method.Results The positive expression of DLC-1 in cervical squamous cell carcinoma,cervical intraepithelial neoplasia,and normal cervical tissue,were 27.4%,76.3%,and 92.3%respectively,the difference was statistically significant(P<0.05);The positive expression of DLC-1 in high,middle,and low pathological grade were 42.9%、27.9%、16.7%respectively,the difference was statistically significant(P<0.05);The positive expression of DLC-1 inⅠ~Ⅱa was 41.4%,which was significantly higher thanⅡb~Ⅳ15.2%(P<0.05);The positive expression of DLC-1 in patients without lymph node metastasis was 34.9%,which was significantly higher than patients with lymph node metastasis 10.5%(P<0.05)。The positive expression of cyclinD1 in cervical squamous cell carcinoma,cervical intraepithelial neoplasia,and normal cervical tissue,were 66.1%,5.3%,0% respectively,the difference was statistically significant(P<0.05);The positive expression of cyclinD1 in high,middle,and low pathological grade were 42.9%,67.4%,75.0%respectively,the difference was statistically significant(P<0.05);The positive expression of cyclinD1 inⅠ~Ⅱa was 48.3%,which was significantly higher thanⅡb~Ⅳ81.8% (P<0.05);The positive expression of cyclinD1 in patients without lymph node metastasis was 58.1%,which was significantly higher than patients with lymph node metastasis 84.2%(P<0.05).The expression of DLC-1 and cyclinD1 in cervical squamous cell carcinoma showed a negative correlation(r=-0.519,P<0.05).Conclusion The expression of DLC-1 in squamous cell carcinoma is lower,and expression of cyclinD1 in squamous cell carcinoma is higher,and both of them are closely related to the stage,grade,and lymph node metastasis of squamous cell carcinoma.
Squamous cell carcinoma;DLC-1;CyclinD1
R4
A
1674-0742(2015)08(a)-0014-03
2015-05-08)