尼古丁诱导肺癌细胞上皮间质转化促进其侵袭转移

背景与目的我们的前期研究发现尼古丁能诱导肺癌细胞上皮间质转化。本研究的目的是探讨尼古丁诱导的上皮间质转化（epithelial-mesenchymal transition, EMT）与肺癌侵袭之间的关系。方法应用不同浓度尼古丁处理肺腺癌A549细胞,应用Real-time PCR和Western blot方法检测EMT相关分子标志物E-钙粘蛋白（E-cadherin）和波形蛋白（Vimentin）mRNA和蛋白表达水平,应用免疫荧光技术检测β-链蛋白（β-catenin）蛋白表达位置的变化,应用划痕实验和Transwell小室侵袭实验检测尼古丁对肺癌细胞迁移侵袭能力的影响。结果尼古丁明显下调肺癌细胞株A549 E-cadherin mRNA和蛋白水平表达（P<0.01, P<0.01）,并具有浓度和时间依赖性;尼古丁明显上调肺癌细胞株A549 Vimentin mRNA和蛋白水平表达（P<0.01, P<0.01）;尼古丁诱导肺癌细胞株A549细胞β-catenin蛋白发生核转移;划痕实验和侵袭实验观察到尼古丁处理的肺癌细胞株A549细胞的迁移和侵袭能力明显增强（P<0.01, P<0.01）。结论尼古丁能够诱导肺癌细胞发生EMT,并且促进肺癌细胞株A549细胞的体外侵袭潜能。     

H2AX磷酸化抑制肺癌细胞发生上皮-间质转化的作用机制

背景与目的：上皮-间质转化（epithelial-to-mesenchymal transition,EMT）是肿瘤细胞发生转移的关键生物学过程,阻碍EMT将抑制肿瘤转移,因此阐明EMT的分子机制具有重要意义。抑癌蛋白H2AX调控肿瘤细胞凋亡相关基因表达,进而产生抗肿瘤作用。揭示H2AX与EMT的关系,探讨H2AX调控肺癌细胞EMT可能的作用机制。方法：利用5%胎牛血清诱导肺癌A549稳定株细胞（包括H2AX基因沉默、H2AX过表达和H2AX磷酸化位点突变）产生EMT。采用蛋白质印迹法（Western blot）和实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR）检测肿瘤细胞EMT标志性分子E-cadherin和vimentin的表达、以及其他EMT相关蛋白血管内皮生长因子受体2（vascular endothelial growth factor receptor 2,VEGFR2）等分子的表达。采用transwell实验分析肺癌A549细胞的迁移和侵袭能力。结果：基因沉默肺癌A549细胞H2AX导致E-cadherin蛋白和mRNA水平下调以及vimentin蛋白和mRNA水平的上调,并增强A549细胞的迁移和侵袭能力。肺癌A549细胞过表达H2AX则上调E-cadherin蛋白和mRNA、下调vimentin蛋白和mRNA,抑制A549细胞的迁移和侵袭;H2AX磷酸化位点突变则部分消除H2AX对E-cadherin上调和vimentin的下调作用以及H2AX对A549细胞EMT的抑制作用;肺癌A549细胞中H2AX基因沉默则刺激VEGFR-2表达,过表达H2AX则抑制VEGFR-2表达;H2AX磷酸化位点突变则消除H2AX对VEGFR-2表达的抑制作用;基因沉默A549细胞中VEGFR-2则抑制EMT作用;H2AX基因沉默刺激肺癌A549细胞EMT相关因子Slug和β-catenin的表达,过表达H2AX抑制Slug和β-catenin表达;H2AX磷酸化位点突变后则消除H2AX对Slug和β-catenin表达的抑制作用。结论：γH2AX通过下调VEGFR-2以及Slug和β-catenin表达进而抑制肺癌A549的EMT过程。     

β-catenin对非小细胞肺癌细胞A549顺铂耐药作用及机制的探讨

目的:探讨β-catenin介导的信号通路在人非小细胞肺癌顺铂(DDP)耐受中的作用及可能机制.方法:MTS法检测人非小细胞肺癌A549及其衍生的DDP耐受细胞A549/DDP对DDP的敏感性;蛋白质印迹法检测A549和A549/DDP细胞内β-catenin及其靶基因Survivin和Bcl-2的蛋白表达,并以TCF/LEF报告基因检测β-catenin的活性;实时定量PCR检测Survivin和Bcl-2的转录水平;将β-catenin反义寡核苷酸片段转染入A549/DDP细胞沉默β-catenin的表达,MTS检测干扰前后细胞对DDP的敏感性,实时定量PCR及蛋白质印迹法检测相关基因的表达.结果:A549/DDP对DDP的耐受性是A549细胞的3.14倍,P=0.006 9;A549/DDP细胞中β-catenin蛋白含量上调且其活性上调4.28倍(P=0.003 6),β-catenin的靶基因Survivin及Bcl-2在mRNA及蛋白水平均上调;干扰下调A549/DDP细胞中β-catenin 明显下调了Survivin及Bcl-2的mRNA及蛋白水平,增加了对DDP的敏感性.结论:β-catenin在耐药细胞A549/DDP对DDP的耐受中起着重要作用,是逆转肺癌DDP耐受的可能潜在靶标.     

纳米雄黄对肺癌A549细胞增殖影响及其机制的探讨

目的:探讨纳米雄黄对肺癌A549细胞增殖的影响及其可能机制.方法:制备纳米雄黄,体外培养肺癌A549细胞株.实验分组:对照组,纳米雄黄干预组(10％和25％纳米雄黄),DDP干预组(2μg/mL),10％联合组(10％纳米雄黄+ DDP),25％联合组(25％纳米雄黄+DDP).运用免疫组化法测定β-catenin蛋白表达情况,RT-PCR法检测c-myc mRNA表达.结果:肺癌A549细胞在加入纳米雄黄干预下,β-catenin蛋白表达与c-myc mRNA表达均受到不同程度的抑制,对照组、10％纳米雄黄组、25％纳米雄黄组、DDP组、10％联合组及25％联合组的β-catenin蛋白表达阳性率分别为(78.26±5.21)％、(53.64±5.57)％、(50.82±4.39)％、(45.26±3.75)％、(31.22±1.63)％和(24.07±1.15)％,c-myc mRNA相对表达量依次为(0.41±0.030)％、(0.35±0.015)％、(0.30±0.018)％、(0.26±0.019)％、(0.14±0.012)％及(0.06±0.010)％；与对照组相比,随着纳米雄黄药物浓度的增加及联用化疗药物,β-catenin蛋白表达阳性率逐渐降低,c-myc mRNA的表达量不断下降,纳米雄黄抑制作用与药物浓度呈依赖性,药物浓度越大抑制作用越明显,并且与化疗药DDP联用具有协同作用.结论:纳米雄黄可通过降低β-catenin及c-myc mRNA在肺癌A549细胞中的表达,阻断Wnt信号转导通路,有效抑制细胞增殖发挥抗肿瘤作用.     

β-catenin在膀胱癌上皮-间质转化中的作用及相关机制

目的:探讨β-catenin在膀胱癌上皮-间质转化(epithelial-mesenchymal transition,EMT)过程中的作用以及相关分子机制。方法:利用siRNA靶向沉默膀胱癌细胞系T24细胞的β-catenin基因,并利用Real-time quantitative PCR和Western blot实验验证siRNA敲减效率。通过Transwell实验检测β-catenin敲减后T24细胞的侵袭能力,进一步使用Real-time quantitative PCR和Western blot实验检测β-catenin敲减后T24细胞的EMT相关标志物的变化。最后,通过下载TCGA数据库,并分析β-catenin与EMT相关标志物的相关性。结果:我们成功在mRNA和蛋白水平上沉默了β-catenin。通过Transwell实验发现,与对照组相比,β-catenin敲减组细胞的侵袭能力下调。与对照组相比,β-catenin敲减组的Slug蛋白、Vimentin蛋白和mRNA下调,E-cadherin蛋白和mRNA上调。通过分析TCGA数据库发现,β-catenin与Slug（r=0.183 5,P=0.000 2）和Vimentin (r=0.190 3,P=0.000 1)均呈正相关。结论:β-catenin通过调控Slug的表达从而调控膀胱癌细胞的EMT。     

Shugoshin1参与NSCLC细胞多西紫杉醇耐药的机制探讨

目的:探讨SGO1（Shugoshin1）参与非小细胞肺癌（non-small cell lung cancer,NSCLC）细胞A549对多西紫杉醇耐药的可能机制。方法:成功构建SGO1过表达细胞株A549-SGO1,利用RT-PCR和Western-blot进行鉴定;通过RT-PCR和免疫荧光检测A549-Vector细胞及A549-SGO1细胞中上皮间质转化（epithelial-mesenchymal transition,EMT）相关标志物的表达情况;通过RT-PCR和Western-blot检测EMT相关转录因子Twist2的表达情况。结果:与A549-Vector细胞相比,A549-SGO1细胞中上皮相关标志物E-cadherin和ZO-1的表达明显降低,而间质相关标志物Fibronectin和Vimentin表达明显升高,EMT相关转录因子Twist2的表达也明显升高。结论:SGO1可能通过Twist2介导EMT进而参与NSCLC细胞株A549对多西紫杉醇的耐药。     

上皮-间叶转变相关蛋白在非小细胞肺癌中的表达及其预后意义

背景与目的:非小细胞肺癌(non-small cell lung cancer,NSCLC)患者最主要的死亡原因是手术后肿瘤转移,而上皮-间叶转变(epithelial-mesenchymal transitions,EMT)是肿瘤发生侵袭、转移的重要原因.本研究探讨EMT相关蛋白Snail、Vimentin、E-cadherin和B-catenin在NSCLC患者中的表达及其预后意义.方法:采用组织芯片技术和免疫组织化学EnvVision两步法检测Snail、Vimentin、E-cadherin和β-catenin蛋白在165例NSCLC患者中的表达情况.根据免疫组织化学结果对NSCLC患者分组,分析Snail、Vimentin、E-cadherin和β-catenin蛋白在判断患者预后和生存情况中的作用.结果:165例NSCLC患者中,Snail、Vimentin、E-cadherin和β-catenin的阳性表达率分别为45.5%、33.9%、66.7%和50.9%.E-cadherin 的表达与Snail呈负相关(P＜0.001),而与β-catenin的表达呈正相关(P=0.003).Snail、Vimentin、E-cadherin/β-catenin复合体异常表达组的生存期均显著低于正常组(P=0.005 9,P=0.025 7,P=0.002 5).上述任意两个蛋白的异常表达是一个独立的预后因素(P＜0.001).结论:EMT相关蛋白Snail、Vimentin和E-cadherin/β-catenin复合体三者中的任意2种蛋白异常表达可作为判断患者预后的独立指标.     

SOX4对非小细胞肺癌细胞A549的顺铂耐药作用的影响

背景与目的 肺癌是最严重的恶性肿瘤之一,其中非小细胞肺癌发病率在肺癌中居首位.部分患者对顺铂耐受是导致化疗失败的主要原因.SOX4是转录调节因子,在多种肿瘤的发生发展过程中发挥着重要的作用,通过调控β-catenin的表达对Wnt信号通路进行调控.本研究旨在探讨SOX4对非小细胞肺癌细胞A549的顺铂耐药作用的影响.方法 体外诱导法建立顺铂耐药的肺癌细胞株A549/DDP,CCK8法检测A549及A549/DDP细胞对顺铂的耐药性.绘制A549与A549/DDP细胞生长曲线.Western blot检测耐药细胞株中SOX4的蛋白表达水平.CCK8法检测敲减SOX4后耐药细胞株A549/DDP对顺铂耐药性.实时定量PCR和免疫印迹法检测敲减SOX4后A549/DPP细胞中β-catenin和Survivin蛋白的表达.结果 成功构建非小细胞肺癌顺铂耐药细胞株A549/DDP,其耐药性是亲本细胞的13.7倍,差异有统计学意义(P<0.001).生长曲线显示耐药细胞株与亲本细胞增殖速度没有统计学差异(P<0.05);与A549细胞相比,耐药细胞A549/DDP细胞中SOX4的表达显著增高(P<0.001).敲减SOX4后,A549/DDP细胞的耐药性显著降低;敲减SOX4后,A549/DDP细胞中β-catenin和Survivin的mRNA和蛋白表达水平显著降低.结论 SOX4的表达水平影响非小细胞肺癌细胞A549对顺铂的耐药性.     

FUNDC1调控肺癌A549细胞及其干细胞的生长、自噬、凋亡和细胞干性的研究

目的:本实验旨在阐明线粒体自噬受体蛋白FUNDC1(FUN 14 domain containing 1)在肺癌病理进程中对肿瘤细胞生长死亡以及细胞干性的调控作用。方法:使用RT-qPCR分析FUNDC1在肺癌组织和细胞中的表达情况。siRNAs和过表达载体转染A549细胞以及诱导形成的A549干细胞团(A549/CSC)。采用CCK-8增殖试剂盒及集落形成实验分析不同处理对肺癌细胞增殖的影响。Western blotting检测FUNDC1、细胞自噬相关蛋白(Beclin-1、LC3-Ⅱ、p62)、凋亡相关蛋白(Bax、Bcl-2、caspase3)和细胞干性相关蛋白(CD133、Sox2、Oct4)的表达。细胞凋亡试剂盒(Elisa)用于测定细胞凋亡水平。流式细胞术分析CD133细胞阳性率。结果:FUNDC1在肺癌组织及细胞中表达上调,干扰FUNDC1抑制A549细胞增殖和保护性自噬,同时诱导细胞凋亡。此外,FUNDC1与CD133表达显著正相关,干扰FUNDC1可显著抑制细胞干性相关基因CD133、Sox2、Oct4的表达。A549/CSC细胞的FUNDC1表达高于正常A549细胞。干扰FUNDC1同样会抑制A549/CSC细胞增殖和保护性自噬,促进细胞凋亡。结论:FUNDC1调控肺癌细胞及CSC细胞的生长、自噬、凋亡及细胞干性。     

肺泡上皮细胞间质转化对肺癌细胞转移影响的研究

目的:通过以TGF-β1诱导肺腺癌细胞系A549细胞出现上皮细胞-间质细胞转化(EMT),并探讨EMT过程的信号转导途径及肺EMT与肺癌转移之间的关系。方法:体外培养A549细胞,以TGF-β1进行干预,收集不同时段的细胞,用荧光实时定量PCR检测上皮及间质细胞标志的mRNA表达,蛋白质印迹法检测上皮及间质细胞标志的蛋白表达、信号转导蛋白P-Smad2/3、Snail1和Snail2的表达及基质金属蛋白酶MMP-2和MMP-9的表达,通过倒置相差显微镜观察肺EMT过程中细胞形态学的变化。结果:TGF-β1干预后,A549细胞上皮细胞标志(E-cad、CK19)的mRNA和蛋白表达下调(P<0.01),间质细胞标志(Vimentin、α-SMA)的mRNA和蛋白表达上调,P<0.05;信号转导蛋白P-Smad 2/3和Snail1上调(P<0.05),Snail2弱表达,P>0.05;基质金属蛋白酶MMP-2上调(P<0.05),MMP-9弱表达,P>0.05;倒置相差显微镜观察到TGF-β1干预后A549细胞由鹅卵石状变为梭形,形态如同肌纤维母细胞。结论:在TGF-β1的诱导下,肺腺癌细胞从上皮细胞向间质细胞转化,其与Smad 2/3和Snail1信号转导途径相关,同时伴随了MMP-2的表达增强,因此肺泡上皮细胞向间质细胞的转化可能通过改变细胞形态学和增加基质金属蛋白酶的表达,增强了癌细胞的侵袭性,促进肺癌的转移。而通过阻断肺癌细胞的EMT过程及其信号转导途径有可能抑制肺癌的转移。     

Rationale and design of the National Program of Cancer Registries' breast, colon, and prostate cancer patterns of care study

Background: Investigators from the Centers for Disease Control and Prevention (CDC), National Program of Cancer Registries (NPCR), are collaborating with public health professionals from seven states and the District of Columbia to conduct the Patterns of Care study to assess the quality of cancer data and to determine whether stage-specific treatments are being carried out. Methods: To assess the quality and completeness of cancer care data in the United States, trained staff from the Patterns of Care study are abstracting medical records to obtain detailed clinical data on treatment, tumor characteristics, stage at diagnosis, and demographics of representative samples of patients diagnosed with breast, colon, and prostate cancer. Altogether staff from each of the eight participating cancer registries will abstract 500 cases of breast, prostate, and colon/rectum/anus cancer for the CONCORD study and an additional 150 cases of localized breast cancer, 100 cases of stage III colon cancer, and 100 cases of localized prostate cancer for the Patterns of Care study. Chi-square tests will be used to compare routine registry data with re-abstracted data. The investigators will use logistic regression techniques to describe the characteristics of patients with localized breast and prostate cancer and stage III colon cancer. Age, race, sex, type of insurance, and comorbidity will be examined as predictors of the use of those treatments that are consistent with consensus guidelines. The investigators plan to use data from the CONCORD study to determine whether treatment factors are the reason for the reported differences between relative survival rates in the United States and Europe. Conclusions Results from the methodology used in the Patterns of Care study will provide, for the first time, detailed information about the quality and completeness of stage and treatment data that are routinely collected by states participating in the NPCR. It will add significantly to our understanding of factors that determine receipt of treatment in compliance with established guidelines. As part of the CONCORD study, it will also examine differences in survival among cancer patients with breast, prostate, and colon/rectum/anus cancers in the United States and Europe.     

Survival outcome of women with synchronous cancers of endometrium and ovary: a 10 year retrospective cohort study

Objective

Synchronous occurrence of endometrial and ovarian tumors is uncommon, and they affect less than 10% of women with endometrial or ovarian cancers. The aim of this study is to describe the epidemiological and clinical factors; and survival outcomes of women with these cancers.

Methods

This is a retrospective cohort study in a large tertiary institution in Singapore. The sample consists of women with endometrial and epithelial ovarian cancers followed up over a period of 10 years from 2000 to 2009. The epidemiological and clinical factors include age at diagnosis, histology types, grade and stage of disease.

Results

A total of 75 patients with synchronous ovarian and endometrial cancers were identified. However, only 46 patients met the inclusion criteria. The median follow-up was 74 months. The incidence rate for synchronous cancer is 8.7% of all epithelial ovarian cancers and 4.9% of all endometrial cancers diagnosed over this time frame. Mean age at diagnosis was 47.3 years old. The most common presenting symptom was abnormal uterine bleeding (36.9%) and 73.9% had endometrioid histology for both endometrial and ovarian cancers. The majority of the women (78%) presented were at early stages of 1 and 2. There were 6 (13.6%) cases of recurrence and the 5 year cumulative survival rate was at 84%.

Conclusion

In our cohort, we found that majority of women afflicted with synchronous cancer of the endometrium and ovary were younger at age of diagnosis, had early stage of cancer and good survival.     

Cancer surveillance behaviors and psychosocial factors among long‐term survivors of breast cancer

BACKGROUND:

Little is known about cancer surveillance (mammography, clinical breast examination, and pelvic examination) behaviors in long‐term (9‐16 years) breast cancer survivors. This report describes the relation of these behaviors to demographic and clinical characteristics, psychological symptoms, body satisfaction, and social support.

METHODS:

Survivors who had participated in Cancer and Leukemia Group B treatment Trial 8541 completed a survey that included questions on breast cancer surveillance and pelvic examination, psychological well being, body satisfaction, and social support.

RESULTS:

The participation rate was 78% and included 245 breast cancer survivors. Survivors (n = 107; 44%) reported completing breast cancer surveillance (mammography and clinical breast examination) and completing pelvic examination (n = 162; 68%) within recommended guidelines. There were no significant associations between breast cancer surveillance and breast cancer anxiety, depression, stressful life events, body satisfaction, social support, or demographic characteristics. Survivors within recommended guidelines for pelvic examinations were younger (P = .05), married (P = .003), had health insurance (P = .004), and had lower depression scores (P = .005) than survivors who underused or overused pelvic examination. In addition, survivors within recommended pelvic examination guidelines had significantly lower levels of breast cancer anxiety (P = .03) compared with survivors who underused pelvic examination.

CONCLUSIONS:

Many long‐term breast cancer survivors were not within recommended cancer surveillance guidelines. Private health insurance was associated with following recommendations for pelvic examinations, although such a relation did not exist for breast cancer surveillance. The results of this study have implications for the development of educational programs to improve cancer surveillance among the growing population of long‐term breast cancer survivors. Cancer 2009. © 2009 American Cancer Society.     

Evaluation of predictive factors for local tumour control after electron-beam-rotation irradiation of the chest wall in locally advanced breast cancer

Background and purpose: Different radiotherapy techniques are being used for chest wall irradiation after mastectomy. We review our results with the electron-beam-rotation technique in a series of 130 high risk breast cancer patients. The main end point of the study was local tumour control; secondary end points were disease free survival, and overall survival, as well as acute and late side effects.

Material and methods: From January 1990 to June 1995, 89 patients underwent electron-beam-rotation irradiation of the chest wall after primary mastectomy and axillary lymph node dissection (group I) and 41 patients after excision of local recurrent breast cancer (group II) with 4×2.5 Gy/week to 50 Gy total dose (4–12 MeV electrons depending on the thickness of the chest wall). In addition, irradiation of local-regional lymph nodes and/or a local boost of 10 Gy were applied dependent on the resection and node status.

Results: After a median follow up of 29 months (65% stadium III/IV) the 3 year local tumour control, disease free survival, and overall survival were 73%, 47%, and 75%, respectively. Local control in group I was 78% versus 60% in group II. Significant predictors for local tumour control, disease free survival, and overall survival were resection status (R0 versus R1/2) and estrogen receptor status (positive versus negative). In group I, tumour grading (GI-IIa versus GIIb-III) and estrogen receptor status were found to be additional significant prognostic factors for complete resected tumours. Five patients developed symptomatic pneumonitis (< 4%) and one patient developed a chronic fistula at the resection. A significant correlation between the degree of acute skin reaction and persistent pigmentation was observed.

Conclusion: In high risk breast cancer patients postoperative irradiation with the electron-beam-rotation technique of the chest wall is an effective therapy resulting in 78% local tumour control at 3 years for locally advanced breast cancer and 60 % for recurrent disease. The rate of acute and late toxicity is low. The degree of acute skin reaction correlates with the degree of persistent pigmentation.     

Meta-analysis of 16 studies of the association of alcohol with colorectal cancer

Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol–CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88–0.98, p = 0.005), heavy drinking (2–3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99–1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11–1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.     

Socio-economic differences in incidence rates of cancers of the male genital organs in Finland, 1971-95

We studied social class variation in the incidence of cancers of the prostate, testis, penis and scrotum among 1.1 million Finnish men (45-69 years of age) during 1971-95. The incidence of prostate cancer (6,972 cases) was increasing during the study period; the highest at all the times occurred in Social Class I (highest social class), 40-50% higher than in Social Class IV (lowest). The social class gradient was strongest in localized disease but there was some variation in incidence of non-localized prostate cancer. A total of 174 testicular cancer cases were diagnosed during the study period. In the early 1970s, the incidence of testicular cancer in Social Class I was 5-fold compared to Social Classes III and IV. Thereafter, the incidence rate decreased in Social Class I, but increased in the lower classes. The positive social class gradient was similar for seminomas and non-seminomas. For penile cancer (n = 128), the incidence decreased over time and social class variation was small. Only 6 cases of scrotum cancer were observed. In testicular cancer the strong positive social class association in the early 1970s is disappearing along with converging incidence trend slopes in different social classes. The difference diminished to less than 2-fold in the 1990s. Reasons for this observation remain open.