Clinical and pathological characteristics and expression of related molecules in patients with airway disseminated lung adenocarcinoma

Objective:Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds,in addition to considerable differences in clinical pathology and molecular biological characteristics.Among these,the phenomenon of spread through air space(STAS),a distinct mode of lung cancer infiltration,has rarely been reported.Therefore,this study aimed to explore the relationship between STAS tumor cells and the clinical and molecular characteristics of patients with lung adenocarcinoma,as well as their impact on prognosis.Methods:This study included 147 patients who were diagnosed with lung adenocarcinoma at the Inner Mongolia Autonomous Region Cancer Institute between January 2014 and December 2017.Surgical resection specimens were retrospectively analyzed.Using univariate and multivariate Cox analyses,we assessed the association between STAS and the clinicopathological features and molecular characteristics of patients with lung adenocarcinoma.Furthermore,we investigated the effects on patient prognosis.In addition,we developed a column–line plot prediction model and performed internal validation.Results:Patients with positive STAS had a significantly higher proportion of tumors with a diameter≥2 cm,with infiltration around the pleura,blood vessels,and nerves,and a pathological stage>IIB than in STAS-negative patients(P<0.05).Cox multivariate survival analysis revealed that clinical stage,STAS status,tumor size,and visceral pleural invasion were independent prognostic factors influencing the 5-year progression-free survival in patients with lung adenocarcinoma.The predictive values and P values from the Hosmer-Lemeshow test were 0.8 and 0.2,respectively,indicating no statistical difference.Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.884 and 0.872 for the training and validation groups,respectively.The nomogram model exhibited the best fit with a value of 192.09.Conclusions:Clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis are independent prognostic factors for patients with STAS-positive lung adenocarcinoma.The nomogrambased on the clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis showed good accuracy,differentiation,and clinical practicality.

Effect of autotransfusion system on tumor recurrence and survival in hepatocellular carcinoma patients

AIM:To investigate the therapeutic efficacy and safety of continuous autotransfusion system(CATS) during liver transplantation of hepatocellular carcinoma patients.METHODS:Eighty-three hepatocellular carcinoma(HCC) patients who underwent liver transplantation with intraoperative CATS(n = 24,CATS group) and without(n = 59,non-CATS group) between April 2006 and November 2011 at the Liver Transplant Institute of Inonu University were analyzed retrospectively.Postoperative HCC recurrence was monitored by measuring alpha-fetoprotein(AFP) levels at 3-mo intervals and performing imaging analysis by thoracoabdominal multidetector computed tomography at 6-month intervals.Inter-group differences in recurrence and correlations between demographic,clinical,and pathological data were assessed by ANOVA and χ 2 tests.Overall and disease-free survivals were calculated by the univariate Kaplan-Meier method.RESULTS:Of the 83 liver transplanted HCC patients,89.2% were male and the overall mean age was 51.3 ± 8.9 years(range:18-69 years).The CATS and nonCATS groups showed no statistically significant differences in age,sex ratio,body mass index,underlying disease,donor type,graft-to-recipient weight ratio,Child-Pugh and Model for End-Stage Liver Disease scores,number of tumors,tumor size,AFP level,Milan and University of California San Francisco selection criteria,tumor differentiation,macrovascular invasion,median hospital stay,recurrence rate,recurrence site,or mortality rate.The mean follow-up time of the nonCATS group was 17.9 ± 12.8 mo,during which systemic metastasis and/or locoregional recurrence developed in 25.4% of the patients.The mean follow-up time for the CATS group was 25.8 ± 15.1 mo,during which systemic metastasis and/or locoregional recurrence was detected in 29.2% of the patients.There was no significant difference between the CATS and non-CATS groups in recurrence rate or site.Additionally,no significant differences existed between the groups in overall or disease-free survival.CONCLUSION:CATS is a safe procedure and may decrease the risk of tumor recurrence in HCC patients.

Detection of disseminated pancreatic cells by amplification of cytokeratin-19 with quantitative RT-PCR in blood,bone marrow and peritoneal lavage of pancreatic carcinoma patients

AIM： To evaluate the diagnostic potential of cytokeratin-19 （CK-19） mRNA for the detection of disseminated tumor cells in blood, bone marrow and peritoneal lavage in patients with ductal adenocarcinoma of the pancreas. METHODS： Sixty-eight patients with pancreatic cancer （/7 = 37）, chronic pancreatitis （n = 16）, and non-pancreatic benign surgical diseases （/7 = 15, control group） were included in the study. Venous blood was taken preoperatively, intraoperatively and at postoperative d 1 and 10. Preoperative bone marrow aspirates and peritoneal lavage taken before mobilization of the tumor were analyzed. All samples were evaluated for disseminated tumor cells by CK-19-specific nested-PCR and quantitative fluorogenic RT-PCR. RESULTS： CK-19 mRNA expression was increased in 24 （64%） blood samples and 11 （30%） of the peritoneal lavage samples in the patients with pancreatic cancer. In 15 （40%） of the patients with pancreatic cancer, disseminated tumor cells were detected in venous blood and bone marrow and/or peritoneal lavage. In the peritoneal lavage, the detection rates were correlated with the tumor size and the tumor differentiation. CK-19 levels were increased in pT3/T4 and moderately/poorly differentiated tumors （G2/G3）. Pancreatic cancer patients with at least one CK-19 mRNA-positive sample showed a trend towards shorter survival. Pancreatic cancer patients showed significantly increased detection rates of disseminated tumor cells in blood and peritoneal lavage compared to the controls and the patients with chronic pancreatitis. CONCLUSION： Disseminated tumor cells can be detected in patients with pancreatic ductal adenocarcinorna by CK-19 fluorogenic RT-PCR. In peritoneal lavage, detection rate is correlated with tumor stage and differentiation. In the clinical use, CK-19 is suitable for the distinction between malignant and benign pancreatic disease in combination with other tumor-specific markers.

Correlation between sodium-iodide symporter expression and circulating tumor cell positivity in differentiated thyroid carcinoma

Objective We investigated the correlation between the expression of the sodium-iodide symporter(NIS) and the detection of circulating tumor cells(CTCs) in differentiated thyroid carcinoma(DTC).Methods NIS expression in differentiated thyroid and the positive rate of CTCs in the peripheral blood were determined by immunohistochemistry S-P and flow cytometry from the records of 172 cases of differentiated thyroid carcinoma.Results Seventy-six cases(44.2%) expressed NIS in the differentiated thyroid and 63 cases(36.6%) were positive for CTCs in the peripheral blood. There was a significant difference between N0 and N1 in the expression of NIS(χ~2 = 6.015, P = 0.014) and the positive rate of CTCs(χ~2 = 14.035, P = 0.001). N0 and N1 also differed significantly in the expression of NIS(r =-0.383,-0.610, P = 0.002, < 0.001). The differences in the NIS expression, but not in the positive rate of CTCs, were significant among the different pathological subtypes(χ~2 = 7.897, P = 0.005; χ~2 = 1.455, P = 0.228, respectively). There was a significant negative correlation between the highly differentiated type and intermediate differentiation type both in the expression of NIS and positive rate of CTCs(r =-0.591,-0.443, P < 0.001, P = 0.002). Conclusion There was a significant negative correlation between the expression of tissue NIS and positive rate of CTCs in the peripheral blood in DTC. The malignancy level and lymph node metastasis in differentiated thyroid carcinoma were negatively correlated with NIS expression and positively correlated with the positive rate of CTC.

Colorectal cancer and dormant metastases:Put to sleep or destroy?

After reading the review by An et al“Biological factors driving colorectal cancer metastasis”,which covers the problem of the metastasis of colorectal cancer(CRC),I had a desire to discuss with readers one of the exciting problems associated with dormant metastases.Most deaths from CRCs are caused by metastases,which can be detected both at diagnosis of the primary tumor and several years or even decades after treatment.This is because tumor cells that enter the bloodstream can be destroyed by the immune system,cause metastatic growth,or remain dormant for a long time.Dormant tumor cells may not manifest themselves throughout a person’s life or,after some time and under appropriate conditions,may give rise to the growth of metastases.In this editorial,we will discuss the most important features of dormant metastases and the mechanisms of premetastatic niche formation,as well as factors that contribute to the activation of dormant metastases in CRCs.We will pay special attention to the possible mechanisms involved in the formation of circulating tumor cell complexes and the choice of therapeutic strategies that promote the dormancy or destruction of tumor cells in CRCs.

Molecular biomarkers for the detection of metastatic colorectal cancer cells

Approximately half of all patients with colorectal cancer develop local recurrence or distant metastasis during the course of their illness. Recently, the molecular detection of metastatic cancer cells in various types of clinical samples, such as lymph nodes, bone marrow, peripheral blood, and peritoneal lavage fluid, has been investigated as a potential prognostic marker. The prognostic value of molecular tumor cell detection was independent of the type of detection method used. As assays become more sensitive and quantitative, a more thorough assessment of the cancer status of patients will be based on molecular markers alone. At present, it is difficult to conclude that one specific molecular marker is superior to others. Comparative analyses are recommended to assess the prognostic impact of molecular analyses in the same patient and determine the biomarkers that provide the most accurate prognostic information.

局限于子宫的内膜癌肿瘤细胞子宫外播散转移的危险因素分析

目的 探讨子宫内膜癌的重要预后因素肿瘤细胞子宫外播散转移的危险因素。方法 收集2015年7月至2022年12月我院同一治疗组收治的子宫内膜癌病例64例,回顾性研究其中有行淋巴结评估结果的45例病例,根据术后病理结果,分析影响淋巴结转移及腹腔肿瘤细胞播散的危险因素。结果 单因素及多因素logistic分析提示,输卵管未结扎是子宫内膜癌肿瘤细胞腹腔播散的独立危险因素(P <0.05),单因素分析提示,CA125升高、组织学类型为非内膜样癌、子宫深肌层浸润为子宫内膜癌淋巴结转移的危险因素(P <0.05),多因素logistic分析中未提示与淋巴结转移有相关的危险因素(P> 0.05)。结论 输卵管结扎与否是子宫内膜癌细胞腹腔播散的独立影响因素,CA125升高、非子宫内膜样癌、子宫深肌层浸润可能是子宫内膜癌淋巴结转移的预测因素。

具有休眠特征的播散肿瘤细胞体内外研究模型的建立及应用

术后无症状的早期癌症(肺癌)患者的转移靶器官中已经潜伏有处于休眠状态的播散肿瘤细胞(DTCs),其增殖是导致临床转移发生的关键环节。开发维持DTCs休眠或根除休眠DTCs的治疗药物,将有望防治肿瘤的转移,进而突破恶性肿瘤整体疗效提高的瓶颈。本文对建立具有休眠特征的DTCs体内外研究模型的方法进行综述,以期促进学者对休眠DTCs的认识,提高抗肿瘤转移药物的研发效率。

Mapping bone marrow niches of disseminated tumor cells

Breast cancer cells may disseminate early, before tumor diagnosis. Disseminated tumor cells, or DTCs, reside in the bone marrow, and may persist for years or even decades. Some of these cells may be re-activated to resume aggressive growth, and eventually become overt bone metastases. Recent studies have begun to shed light on this complicated process and revealed multiple steps and intermediate states of colonizing DTCs. However, how cancer-host interactions evolve during this process needs to be further understood. Most of our current knowledge of the bone microenvironment is obtained through studies looking for the hematopoietic stem cell(HSC) niche. Although this long-standing question has not yet been resolved, our search for the HSC niche has resulted in a detailed map of various cell types in the bone marrow. Furthermore, various techniques used to find the HSC niche may also be adapted for finding the cancer cell niche. In this article, we will review the recent progress in both the DTC and HSC areas with a focus on their potential microenvironment niches. We will also discuss how to apply what we have learned from HSC studies to map DTCs in the bone context. We hope to stimulate thoughts and ideas to further elucidate the bone colonization process, and develop potential therapeutic interventions.

小鼠动物模型中骨髓播散肿瘤细胞的检测方法

目的:探究小鼠骨髓中播散肿瘤细胞(disseminated tumor cells,DTCs)的检测方法。方法:采用慢病毒感染的方法构建MDA-MB-231-GFP/Luc乳腺癌细胞系,将MDA-MB-231-GFP/Luc细胞经左心室接种于NOD-SCID小鼠体内,构建骨髓DTCs小鼠模型。采用荧光定量RT-qPCR、流式细胞计数、骨组织连续切片免疫荧光染色三种检测方法对小鼠骨髓DTCs进行定量和组织学定位研究。结果:荧光定量RT-qPCR法和流式细胞计数法的检测下限分别为22个和25个绿色荧光蛋白阳性(GFP^(+))细胞。骨组织连续切片免疫荧光染色法虽然不能定量骨髓DTCs数量,但可观察到GFP^(+)DTCs在骨组织中的分布,定位于成骨细胞或骨基质附近。结论:三种检测方法联合使用可满足小鼠骨转移研究动物实验中骨髓DTCs的定量和定位研究的需求,可为乳腺癌骨转移和骨髓中休眠癌细胞研究提供方法学支持。

腹腔镜下经自然腔道取标本手术对结直肠癌患者创伤应激反应及脱落肿瘤细胞种植播散的影响

目的探讨腹腔镜下经自然腔道取标本手术对结直肠癌患者创伤应激反应及脱落肿瘤细胞种植播散的影响。方法选取2019年1月至2022年1月收治的60例结直肠癌患者,根据治疗方式不同将其分为对照组和观察组,各30例。对照组采用常规腹腔镜手术治疗,观察组采用腹腔镜下经自然腔道取标本手术治疗。比较两组的治疗效果。结果术后1 d,观察组的皮质醇(Cor)、醛固酮(ALD)、肾上腺素(E)水平低于对照组,差异具有统计学意义(P<0.05)。手术开始时、手术结束前,两组的腹腔灌洗液肿瘤细胞比较,差异无统计学意义(P>0.05);吻合前、吻合后,两组的肠腔灌洗液肿瘤细胞比较,差异无统计学意义(P>0.05)。术后1 d,观察组的免疫球蛋白A(IgA)、免疫球蛋白M(IgM)水平高于对照组(P<0.05)。结论腹腔镜下经自然腔道取标本手术有助于减轻结直肠癌患者创伤应激反应,改善免疫功能,在脱落肿瘤细胞种植播散上与传统腹腔镜手术相比无明显差异。

肝癌肝移植术中肿瘤播散以及与CD44v6及MMP9相关性的研究

目的探讨肿瘤播散细胞检测对肝癌肝移植术中转移的评价意义以及与基质金属蛋白水解酶(MMP-9)、黏附分子(CD44v6)的相关性。方法采用RT-PCR联合荧光标记探针杂交法定量检测30例血清AFP阳性肝癌肝移植患者术前、术中播散肿瘤细胞AFPmRNA表达水平,ELISA法检测肝癌肝移植术前患者血清CD44v6水平,免疫组化法检测MMP9在肿瘤组织中的表达;运用统计软件SPSS9.0行χ2检验、方差分析和t检验。结果30例肝癌肝移植术中肿瘤播散阳性率肺动脉、外周动脉、外周静脉、门静脉分别为63.3%、60%、50%、40%;肝移植手术过程中对肝脏的挤压可以引起肿瘤播散,并且以肺动脉途径为主,P<0.01;术中肿瘤播散组与无肿瘤播散组血清CD44v6水平差异有显著性,P<0.01;术中肿瘤播散组与无术中肿瘤播散组肿瘤组织表达MMP9差异有显著性,P<0.05。结论RT-PCR联合荧光标记探针杂交法能够检测到肝癌患者血液中播散肿瘤细胞,并且以肺动脉血阳性率最高;在肝移植过程中对病肝的搬动、挤压可以引起肿瘤细胞播散;其过程与基质金属蛋白水解酶(MMP-9),黏附分子(CD44v6)相关。

循环肿瘤细胞和播散肿瘤细胞对食管癌患者预后的meta分析

目的用循环肿瘤细胞(CTCs)和播散肿瘤细胞(DTCs)预测食管癌患者的预后仍存在争议,本文旨在探究食管癌患者CTCs/DTCs是否与患者临床病理特征、预后及生存状况存在相关性。方法通过Pub Med、Web of Science、Embase及Cochrane数据库检索所有CTCs/DTCs相关研究。制定文献纳入/排除标准并依此选择文献。以比值比(OR)、相对危险度(RR)、风险比(HR)和95%可信区间(95%CI)作为效应指标,用Review Manager5.3、Stata12.0软件进行计算和分析。结果共纳入19项研究,包含1766例食管癌患者。Meta分析显示,CTCs/DTCs与患者下列临床病理参数:肿瘤分期(OR=1.95)、浸润深度(OR=1.99)、淋巴结转移(OR=2.44SEN)、远处转移(OR=5.98SEN)、分化程度(OR=1.67)、淋巴脉管转移(OR=4.48);预后:复发(RR=6.86SEN)、转移(RR=3.22);生存状况:总体生存率(OS)整体分析(HR=3.46)、无病生存率/无进展生存率(DFS/PFS)整体分析(HR=3.00)显著相关。结论食管癌患者CTCs/DTCs与肿瘤分期、浸润深度、淋巴结转移、远处转移、分化程度、淋巴脉管转移、复发、转移显著相关,也与总体生存率、无病生存率/无进展生存率显著相关。因此,CTCs/DTCs可作为食管癌患者临床预测指标。

肠内营养用于术前肠道准备对结直肠癌患者腹腔和肠腔脱落癌细胞的影响

目的探讨术前肠内营养代替肠道准备对结直肠癌患者腹腔和肠腔脱落癌细胞的影响。方法将经病理确诊的60例结直肠癌患者随机分为两组,每组30人:A组于术前3天起每日口服30ml/kg瑞素,不进行灌肠,不口服泻药和抗生素;B组采用传统肠道准备,包括术前禁食、口服抗生素和清洁灌肠。两组患者均在开腹后用400ml生理盐水冲洗肿瘤所在的局部腹腔,抽取腹腔冲洗液200ml,迅速送检;手术切除肿瘤后作肠吻合之前,用1000ml生理盐水灌洗远端结直肠腔,收集肠腔冲洗液500ml,迅速送检。比较两组患者腹腔和肠腔内脱落的癌细胞阳性率,同时比较其肠道清洁度、术后肛门排气恢复时间和并发症发生率。结果A组患者腹腔和肠腔内脱落癌细胞阳性率分别为3.3%(1/30)和6.7%(2/30),明显低于B组患者的20.0%(6/30)和26.8%(8/30)(P均<0.05)。两组患者的肠道清洁度、术后肛门排气恢复时间和并发症发生率差异均无显著性(P均>0.05)。结论术前肠内营养可减少结直肠癌患者腹腔和肠腔脱落癌细胞的阳性率。

小剂量辐射抑制肿瘤细胞播散的机理研究

观察了静脉注入肿瘤细胞前24h，75mGyX射线全身照射对小鼠免疫功能的影响。结果表明照射组小鼠胸腺S期细胞百分数于照射后4d，胸腺CD3+细胞百分数于照射后2、8d，脾细胞IL－2和γIFN分泌于照射后4d，脾脏NK细胞活性于照射后2、4、6和8d均较假照射组明显增高（P＜0．05～0．01）。提示小剂量辐射增强机体免疫功能可能与其抑制肿瘤细胞播散有关。

肝癌肝移植术前和术中癌细胞血行转移与肿瘤分化、微血管侵犯相关性研究

目的:探讨检测血播散肝癌细胞内AFP-mRNA评估肝癌肝移植术前和术中微转移与肿瘤分化、微血管侵犯的相关性。方法:采用RT-PCR联合荧光标记探针杂交法定量检测30例血清AFP阳性肝癌肝移植患者术前、术中血播散肝癌细胞内AFP-mRNA,病理分析肿瘤分化程度及微血管侵犯。结果:30例肝癌肝移植术前与术中肺动脉、外周动脉、外周静脉、门静脉血中播散肝癌细胞内AFP-mRNA阳性率以及拷贝数有显著差异(P<0.05);术前、中肿瘤播散组与无肿瘤播散组的微血管侵犯有显著差异(P<0.01);术前肿瘤播散组与术前无肿瘤播散组肿瘤分化无显著差异(P>0.05);术中肿瘤播散组与术中肿瘤无播散组肿瘤分化有显著差异(P<0.01)。结论:RT-PCR联合荧光标记探针杂交法能够检测到肝癌患者血液中播散肿瘤细胞,并且以肺动脉血阳性率最高;肝移植手术过程可以引起肿瘤细胞播散,且与肿瘤分化、微血管侵犯相关。

小鼠口腔癌淋巴道转移模型颌下淋巴结播散肿瘤细胞的检测

目的:检测小鼠口腔癌淋巴道转移模型癌变过程不同时期的颌下淋巴结播散肿瘤细胞(disseminated tumor cell,DTC),探讨小鼠口腔癌变过程与颌下淋巴结DTC的关系。方法:病理检查明确诊断为口腔正常组小鼠4只,轻至中度异常增生组8只、重度异常增生组4只,口腔鳞癌无淋巴结转移组、伴淋巴结转移组各4只。采用免疫组织化学指标广谱细胞角蛋白(pancytokeratin,pan-CK)检测颌下淋巴结DTC,比较其差异。结果:口腔正常组0只、轻至中度异常增生组2只,重度异常增生组1只,口腔鳞癌无淋巴结转移组2只,口腔鳞癌伴淋巴结转移组4只颌下淋巴结发现DTC,阳性率分别为0%(0/4)、25%(2/8)、25%(1/4)、50%(2/4)和100%(4/4);随着癌病程度的增加,DTC由簇状分布向片状分布发展。结论:小鼠口腔黏膜恶变过程中,区域淋巴结在轻至中度异常增生时即可检测到DTC,并随癌变程度加重,DTC的发生率及数量不断增加。

喉癌动物模型中播散肿瘤细胞与突变型p53的研究

目的:建立喉癌裸鼠肿瘤模型,进行外周血播散肿瘤细胞(Disseminated tumor cell,DTC)和肿瘤组织突变型p53基因的检测,判断两者之间的相关性及早期预示肿瘤远处转移和预后的价值。方法:从50只裸鼠中随机选择40只建立裸鼠喉癌肿瘤模型,其余10只为对照组,采用套式PCR法,以CK19 mRNA为标记物于肿瘤种植成功后第10周检测肿瘤组及对照组裸鼠外周血中的DTC;以RT-PCR和免疫组化法检测肿瘤组织中突变型p53蛋白表达情况。待裸鼠死亡后解剖肝、肺及淋巴结,采用连续病理切片HE染色证实是否发生转移。结果:肿瘤组DTC阳性率为50.0%(20/40),对照组为阴性,差异有统计学意义(P<0.05)。肿瘤组织中突变型p53阳性率为55.0%(22/40),p53的表达与DTC呈正相关。1年内DTC与突变型p53都为阳性组中位生存期为34周,阴性组为43周,生存差异有统计学意义(P<0.05);阳性组发生远处器官转移率为38.9%(7/18),阴性组转移率12.5%(2/16),差异有统计学意义(P<0.05)。结论:DTC联合突变型p53蛋白阳性表达可以作为早期判断肿瘤转移的指标,是预后不良的一组独立危险因素;DTC与突变型p53蛋白表达存在正相关。

头颈部肿瘤休眠机制的研究进展

癌症术后患者在数年甚至数十年后可见局部复发及远处转移的现象,近来被人们定义为肿瘤的休眠。尽管有很多文献已报道相关内容,但肿瘤休眠及微小残留病的生物学和发病机制仍然不清。目前,肿瘤休眠的机制大致包括3种:血管生成性休眠、免疫性休眠及肿瘤细胞的休眠。本文主要讨论调控肿瘤休眠的潜在机制,重点探讨播散肿瘤细胞(DTC)及其与周围微环境的相互作用。此外,对残留肿瘤细胞的再激活机制进行了阐述,如头颈部肿瘤模型中淋巴结内的肿瘤细胞的再激活。

小鼠口腔癌模型骨髓播散细胞RB1CC1纯合性缺失的初步研究

目的初步探讨小鼠口腔癌模型重度异常增生时期骨髓播散细胞RB1CC1基因纯合性缺失及其意义。方法应用激光捕获显微切割(LCM)技术捕获35张重度异常增生时期小鼠骨髓单个核细胞涂片的单个细胞角蛋白阳性(CK+)细胞,单细胞全基因组扩增技术(WGA)扩增其DNA,PCR检测其视网膜母细胞瘤诱导卷曲蛋白(RB1CC1)的纯合性缺失情况,并与舌部正常、重度异常增生以及鳞癌组织各4例对照。结果 LCM成功捕获CK+细胞35个,WGA成功扩增3个,RB1CC1纯合性缺失情况分别为单个CK+细胞(2/3),舌癌变组织(2/4),舌部正常组织(0/4),重度异常增生组织(0/4)。结论小鼠口腔癌模型重度异常增生时期骨髓CK+细胞有RB1CC1基因纯合性缺失,该时期骨髓CK+细胞可能是播散肿瘤细胞。