184例多原发恶性肿瘤临床特征及其预后分析

目的:探讨多原发恶性肿瘤（multiple primary malignant neoplasms,MPMN）的临床病理特征及其预后。方法:回顾性分析2010年06月至2021年06月我院收治的184例多原发恶性肿瘤病例资料。结果:184例MPMN中,78例为同时性肿瘤（synchronous MPMN,SMPMN）,106例为异时性肿瘤(metachronous MPMN,MMPMN);男性78例,女性106例。最常见的肿瘤依次为消化系统肿瘤、乳腺癌、妇科肿瘤,其中消化系统肿瘤最常见为结直肠癌。SMPMN组中第一肿瘤分期以中晚期为主,而MMPMN组中第一肿瘤分期以早期为主,68%的MMPMN在原发恶性肿瘤诊断后5年内出现第二原发恶性肿瘤。MMPMN组生存时间较SMPMN组生存时间显著延长。消化系统肿瘤相关MPMN预后较其他部位相关MPMN预后更差;乳腺癌相关MPMN预后优于其他部位MPMN。单因素分析显示:性别、年龄、第一肿瘤分期、吸烟史、SMPMN或MMPMN是影响MPMN生存的预后因素。多因素分析显示:第一肿瘤分期是影响肿瘤预后的独立危险因素。结论:随着医疗技术的进步,MPMN的生存率有所提升。原发恶性肿瘤诊断后通过随访以及定期检查早期能够发现第二原发恶性肿瘤。中晚期第一肿瘤、SMPMN、消化系统肿瘤的患者预后更差。     

膀胱癌相关多原发恶性肿瘤49例

目的 研究与膀胱癌相关多原发恶性肿瘤(MPMN)的临床特点.方法 回顾性分析中国医学科学院肿瘤医院1958年至1998年收治的与膀胱癌相关的MPMN患者资料.结果 与膀胱癌相关MPMN 49例,占同期收治的膀胱癌患者的5.7%(49/847).49例膀胱癌均为移行细胞癌,47例为非肌层浸润性癌.膀胱外肿瘤以消化系统肿瘤最多(36.7%).第二原发癌为肺癌,共7例(14.3%).第一、第二原发肿瘤间隔时间平均86.2个月.肿瘤临床分期为Ⅰ～Ⅱ期占90%.以第一或第二原发肿瘤确诊算起,中位生存期分别为104个月和39个月.结论 与膀胱癌相关MPMN中膀胱癌以非肌层浸润性移行细胞癌为主,膀胱外肿瘤以消化系统肿瘤为多.第二原发肿瘤为肺癌时,需注意与膀胱癌肺转移相鉴别.与膀胱癌相关的MPMN积极治疗效果好.     

合并肾细胞癌的多原发恶性肿瘤9例临床分析

目的探讨合并肾细胞癌(RCC)的多原发恶性肿瘤(MPMN)的发病特点、治疗方法及预后,以提高其临床诊治水平。方法回顾性分析9例合并RCC的MPMN患者的临床资料,并随访生存情况。结果 9例患者中,男5例,女4例,确诊时患者的年龄为43~82岁。双原发恶性肿瘤(DPMN)7例,三原发恶性肿瘤2例。合并RCC的MPMN以消化系统和呼吸系统肿瘤最为常见。9例患者的中位生存时间为25个月,2年和3年生存率分别为66.7%和22.2%。结论对恶性肿瘤患者定期随访可以在早期发现其他原发恶性肿瘤,通过临床分析提高对合并RCC的MPMN的认识也将有助于为患者制订恰当的治疗方案。     

原发性和继发性胶质母细胞瘤中p53 、p16 和Rb 的表达及意义

 目的 探讨p53、p16和Rb基因在原发性和继发性GBM中的表达差异性及意义。方法 应用RT—PCR和Western-blot检测14例原发性和16例继发性GBM中p53，p16mRNA和蛋白表达，免疫组织化学法检测Rb表达。结果 Rb免疫组织化学染色显示正常脑组织中无表达，14例原发GBM中有3例表达缺失（21．4％），16例继发GBM中有2例表达缺失（11．1％）。RT-PCR和Westernblot对比原发和继发GBM中p53和p16的表达，发现所有继发GBM中p53表达强度较原发GBM明显增加，14例原发GBM中有5例缺失（36．（1％），继发GBM中仅有1例表达缺失（6．25％）。p16表达缺失明显减少。结论 Rb的表达缺失在原发和继发GBM中没有明显的差异。细胞周期调节基因p53在mRNA和蛋白水平表达增加和p16在同样水平表达缺失是原发与继发GBM重要的细胞周期调控基因上的变化，可能是基因治疗GBM的重要靶点之一。     

46例胃肠道间质瘤临床病理分析

目的　探讨胃肠道间质瘤 (GIST)的组织起源、临床病理和免疫组化特点。方法　对 46例GIST标本进行临床病理观察及免疫组织化学检查。结果　 46例GIST中良性 8例 ,交界性 14例 ,恶性 2 4例 ;瘤细胞为梭形或上皮样 ,或两者混合存在 ;免疫组化表型为CD117和CD3 4,阳性率分别为 95 6%及 67 4%,Desmin及S -10 0少数病例灶性阳性。结论　GIST可能起源于多潜能的、卡哈尔间质细胞样的前体细胞 ,是胃肠道最常见的间叶性肿瘤 ,有较为独特的组织学形态 ,免疫组织化学CD117敏感性强、特异性高 ,是胃肠道间质瘤可靠的标记物 ;CD3 4表达率较高 ,可作为诊断的参考指标     

46例胃肠道间质瘤临床病理分析

目的 探讨胃肠道间质瘤(GIST)的组织起源、临床病理和免疫组化特点。方法 对46例GIST、标本进行临床病理观察及免疫组织化学检查。结果 46例GIST中良性8例，交界性14例，恶性24例；瘤细胞为梭形或上皮样，或两者混合存在；免疫组化表型为CD117和CD34，阳性率分别为95.6％及67．4％，Desmin及S-100少数病例灶性阳。结论 GIST可能起源于多潜能的、卡哈尔间质细胞样的前体细胞，是胃肠道最常见的间叶性肿瘤，有较为独特的组织学形态，免疫组织化学CD117敏感性强、特异性高，是胃肠道间质瘤可靠的标记物；CD34表达率较高，可作为诊断的参考指标。     

抗人乳腺癌单克隆抗体BG6在乳腺癌诊断和鉴别诊断中的应用

本文应用抗人乳腺癌单克隆抗体BG6对26例临床与病理疑难的乳腺疾病进行免疫组织化学研究。对乳腺的原发或继发癌的鉴别诊断13例中,阳性11例,定为原发瘤;阴性2例则为继发瘤。在难分良、恶性诊断8例中,阳性6例,确诊恶性,其余2例阴性为良性。而在恶性淋巴瘤3例中皆为阴性,1例阳性确诊为未分化癌。这一结果表明,抗人乳腺癌单克隆抗体BG6除有其敏感性外,还具有一定的特异性和选择性。它不仅在乳腺癌的鉴别诊断中有一定的实用价值,而且还可望进一步用于乳腺肿瘤的免疫病理研究。     

6例原发肺腺癌乳腺转移的临床特征分析

目的：探讨原发肺腺癌乳腺转移的临床特点。方法回顾性分析6例经病理证实的原发肺腺癌乳腺转移患者的临床资料。结果6例均为女性,5例患者的乳腺转移病灶表现为无痛性、生长迅速的乳腺单发结节,1例表现为弥漫性乳房红肿。乳腺转移可以是原发肺腺癌的首发症状,也可在病程中出现。6例患者乳腺转移灶的病理均为腺癌,免疫组化结果显示：5例患者的雌激素受体为阴性,1例为弱阳性;孕激素受体均为阴性;5例患者甲状腺转化因子1表达强阳性,1例阳性。结论有原发肺腺癌病史和快速增长的乳腺结节患者需考虑乳腺转移。免疫组化是鉴别原发或继发乳腺恶性肿瘤的关键。     

人胰腺癌bcl-2基因的过度表达--免疫组织化学和原位杂交研究

目的 :应用地高辛标记bcl 2cDNA进行mRNA原位杂交和免疫组织化学分析胰腺癌中bcl 2基因的mRNA转录和蛋白翻译 ,研究bcl 2基因结构和功能表达的关系。方法 :以胰腺癌病人癌组织( 50例 )、胰腺癌转移灶组织 ( 15例 )为研究对象 ,采用免疫组织化学 (SP法 )和分子原位杂交法检测bcl 2在胰腺癌中的表达。对照组 10例为慢性胰腺炎组织。结果 :bcl 2蛋白在胰腺癌组明显高于胰腺癌转移灶组 ,Ⅰ、Ⅱ期、无转移、高分化的胰腺癌明显高于Ⅲ、Ⅳ期、有转移和低分化的胰腺癌。免疫组织化学与原位杂交技术检测胰腺癌组织中bcl 2基因表达结果一致。结论 :bcl 2蛋白可能作用于胰腺细胞的癌变阶段 ,并与胰腺导管上皮癌变有关 ;bcl 2基因在mRNA和蛋白水平是相对稳定的     

组织因子表达与直肠癌肝转移及其预后

目的 探讨组织因子（TF）与直肠癌肝转移的关系及其在原发直肠癌中的预后意义。方法 应用免疫组织化学染色法观察40例原发直肠癌组织,3例直肠癌肝转移灶组织和6例直肠良性腺瘤TF的表达特点,结合临床病理资料进行分析。结果 （1）40例原发直肠癌中,20例TF表达阳性,正常黏膜和6例良性腺瘤均无TF表达。（2）直肠癌同时性肝转移和异时性肝转移TF的表达均与肝转移的发生密切相关（P=0.002和P=0。001）.(3)TF是影响原发直肠癌预后的因素之一（P=0.024)。结论 TF可能参与原发直肠癌肝转移的生物学过程,其阳性表达可能作为高危患者术后肝转移的预测指标应用于临床。     

Heterogeneity of Gleason grade in multifocal adenocarcinoma of the prostate

BACKGROUND: The Gleason grading system uniquely combines data from different areas of carcinoma in the same prostate specimen. Prostatic adenocarcinoma often is multifocal, and different Gleason grades may be present in different foci. The current study was undertaken to compare the Gleason grades of individual adenocarcinoma foci in a given specimen with the overall Gleason grades (primary and secondary) of that specimen. METHODS: Data were obtained from 115 consecutive radical prostatectomy specimens via whole-mount processing and complete sectioning. Diagrams were constructed by tracing the outline of each whole-mount section, and tumor maps subsequently were generated. The largest focus was considered the index tumor. Each prostatectomy specimen was assigned primary and secondary Gleason grades, and each tumor focus was assigned its own primary and secondary Gleason grades. Tumor volume was measured using the grid method. RESULTS: Two or more adenocarcinoma foci were present in 87% of all specimens (2 foci, n = 20; 3 foci, n = 33; 4 foci, n = 17; 5 foci, n = 13; > 5 foci, n = 17). Specimens (n = 15) containing a single tumor were excluded from further analysis. Among the remaining specimens (n = 100), all tumor foci had Gleason grades that were the same as the corresponding overall Gleason grades in only 9 cases (9%). The Gleason score (i.e., the sum of the primary and secondary grades) of the index tumor was correlated with the overall Gleason score in 68% of specimens. The primary grade of the index tumor was the same as the overall primary grade in 97 specimens, whereas the secondary grade of the index tumor was the same as the overall secondary grade in only 68 specimens. The primary and secondary grades of the index tumor, compared with the overall Gleason primary and secondary grades, were reversed in 17 specimens. CONCLUSIONS: The findings of the current study demonstrated the histologic heterogeneity of multifocal prostate malignancies. Although the Gleason grading system was used to determine an overall score for prostate carcinoma within a specimen, the scores of individual tumors, including index tumors, often did not agree with this overall score. These findings may have implications with respect to future biomarker and tissue array studies.     

合并宫颈癌的多原发恶性肿瘤临床分析并文献复习（附7例）

目的:探讨合并宫颈癌的多原发恶性肿瘤（multiple primary malignant neoplasms,MPMN）的临床特点、诊治及预后。方法:对2014年8月至2016年12月于我院肿瘤科就诊的7例合并宫颈癌的MPMN患者的临床资料进行回顾性分析，并进行文献复习。结果:合并宫颈癌的MPMN患者占同期收治宫颈癌患者的1.08%。宫颈癌-肺癌、宫颈癌-结直肠癌常见，宫颈癌-非霍奇金淋巴瘤、宫颈癌-胆囊腺癌少见。2例患者行宫颈癌根治术，术后辅以放化综合治疗；5例患者行宫颈癌根治性放疗联合全身化疗。7例患者的其他原发癌均行根治性治疗。患者第一原发癌确诊后中位生存时间33个月，第二原发癌确诊后中位生存时间23个月。结论:合并宫颈癌的MPMN应早期诊断，行宫颈癌根治术联合放疗、化疗，对于其他原发恶性肿瘤也应根治性治疗，可取得较好预后。     

全自动免疫组化与手工染色标记胸腺瘤TdT表达的对比观察

目的:对比观察胸腺瘤TdT在全自动免疫组织化学染色技术(automatic immunohistochemical staining techniques,AIST)和手工染色方法（manual staining method,MSM）中表达的差异性。方法:收集2015年-2016年大坪医院胸腺瘤手术标本21例,经石蜡包埋、切片、染色,显微镜下观察胸腺瘤TdT在AIST和MSM表达的差异。AIST采用Ventana公司生产的BenchMark XT,二抗检测系统分别采用UltraView Universal DAB Detection kit (简称UV)和Optiview DAB IHC Detection kit (简称OV)。结果:手工染色TdT阳性表达定位准确,染色强度强,背景清晰;AIST中采用UV二抗检测系统TdT染色虽然阳性定位准确,但TdT染色强度偏弱,背景不清晰,两者比较具有显著性差异（P＜0.01）。优化染色方案后,改用OV二抗检测系统,TdT染色各项指标优于UV二抗检测系统,染色效果和手工相比,染色强度和阳性率一致。结论:任何抗体指标在行免疫组化前均需进行最适条件的摸索与优化,从而获得该抗体指标最佳的染色方案。     

快速免疫组织化学技术在甲状腺肿瘤术中冷冻诊断中的应用

 目的　探讨快速免疫组化（IHC）新方法及其在甲状腺肿瘤术中冷冻诊断中的应用价值。方法　采用MaxVision快速免疫组化一步法检测CK19、HBME-1、Gla-3在甲状腺乳头状癌（PTC）及甲状腺良性病变组织冷冻切片中的表达,以冰剩组织MaxVision常规IHC作对照。结果　MaxVision快速IHC一步法在20 min内完成,三种标记阳性定位与常规IHC基本对应一致,表达部位CK19位于细胞质和细胞膜,Gla-3、HBME-1以滤泡腔缘或（和）乳头表面为主,表达强度强于常规IHC。冷冻切片快速IHC CK19、HBME-1、Gla-3阳性表达率：良性病变（结节性甲状腺肿、慢性淋巴细胞性甲状腺炎、腺瘤）为0、10.7 %（3／28）、0,PTC为94.9 %（37／39）、92.3 %（36／39）、92.3 %（36／39）,三种标记在甲状腺良性病变与PTC间表达差异均有统计学意义（χ2值分别为59.326、55.861、44.605,均P＜0.05）;同一病例两种以上标记阳性在良性病变为0,PTC为100 %,差异有统计学意义（χ2＝67.000,P＜0.05）。结论　MaxVision快速IHC一步法可以应用于术中冷冻诊断,联合检测CK19、HBME-1、Gla-3对PTC术中冷冻诊断具有较高辅助诊断价值。     

Expression of ras oncogene mRNA and protein in aberrant crypt foci.

The expression of the ras oncogene in aberrant crypt foci was studied by both in situ hybridization and immunohistochemical approaches. Aberrant crypt foci are hypothesized to represent the earliest identifiable microscopic lesions of colon cancer in rodent colons. Sprague-Dawley male rats were injected with azoxymethane (20 mg/kg s.c.) once. Twelve weeks later, aberrant crypt foci were identified topographically, microdissected and processed for histology. In situ hybridization with an antisense oligomer of c-ras demonstrated increased expression of ras-specific RNA in aberrant crypts compared to normal crypts. A low amount of non-specific hybridization was obtained with the corresponding sense oligomer. The percentage of cells with grains (labeling index) was calculated in early and advanced aberrant crypt foci. This index was also calculated in normal appearing crypts. The labeling indices for the early and advanced aberrant crypt foci were significantly greater than that of normal crypts (18.0 and 25.0 versus 11.9). In the same tissue specimens, immunohistochemical staining for ras p21 with the monoclonal antibody (Y13-259) revealed strong staining intensity in early aberrant crypts (15/22) and advanced aberrant crypts (22/30) compared to normal crypts (3/50). The immunohistochemical results demonstrate the presence of elevated levels of ras p21 in the same tissue as increased levels of ras-specific message. This investigation provides the earliest demonstration of increased expression of the ras oncogene in precursor lesions of colon cancer possessing dysplastic features.     

Absence of retinoblastoma protein expression in primary non-small cell lung carcinomas.

Retinoblastoma (RB) protein expression was examined in paraffin and frozen tissue sections of 36 primary non-small cell lung carcinomas (NSCLC) using immunohistochemistry with confirmation by direct Western blotting. A normal RB protein staining pattern was present in 24 and absent in 10 NSCLC. Two additional RB positive primary tumors have major foci in which all tumor cells showed no RB protein staining. Significantly more high-stage (stages III and IV) NSCLC had altered RB protein expression than those with low-stage (stages I and II) tumors (P less than 0.05). The results suggest that absence of the RB expression may be associated with the initiation and/or progression of many NSCLC. This is the first report of successful RB staining in paraffin sections.     

Immunohistochemical detection of occult lymph node metastases in non-small cell lung cancer: anatomical pathology results from Cancer and Leukemia Group B Trial 9761.

PURPOSE: Our purpose was to study the detection of occult metastases (OM) in regional lymph nodes using immunohistochemical stain for cytokeratin, and for this study we targeted clinical stage I patients with non-small cell lung cancer. EXPERIMENTAL DESIGN: The study comprised the first 193 patients entered onto Cancer and Leukemia Group B protocol 9761. All had clinically staged T(1-2)N(0)M(0) non-small cell lung cancer, and all underwent curative resections of their primary tumors. Samples of the primary tumor and lymph nodes were taken from lymph node stations 2-12 and shipped to a central laboratory, where each lymph node was histologically processed and stained with H&E as well as with immunohistochemical stain using antibodies to cytokeratin (AE1/3). RESULTS: Altogether, we examined 825 lymph nodes. Whereas routine H&E staining allowed us to detect 18 positive lymph nodes, immunohistochemical staining allowed us to detect 45 positive lymph nodes (P < 0.0001). There were 28 OM [i.e., those detectable only by immunohistochemistry (IHC)], and there was 1 metastasis detected only by H&E staining. The OM included 9 OM in N1 stations and 19 OM in N2 stations. Twelve patients with OM had skip metastases. Routine H&E staining upstaged six patients to N1, and IHC added another five. Routine H&E upstaged 9 patients to N2, and IHC added another 11. We also uncovered new details about the way in which H&E detection depends on metastatic tumor burden. Specifically, for the probability of detecting metastases by H&E to exceed 0.50, the maximum diameter of the metastasis must be greater than 0.23 mm. CONCLUSIONS: IHC detects greater than twice as many positive regional lymph nodes as does H&E staining, and the foci of tumor it detects are significantly smaller than those detected by H&E staining.     

Multiple primary malignant neoplasms: case report and a comprehensive review of the literature

A case is presented of an elderly patient with synchronous ureteral/bladder/urethral transitional cell carcinoma and prostatic adenocarcinoma. In a subsequent review of 1,104,269 cancer patients in the literature, the reported prevalence of multiple primary malignant neoplasms (MPMN) varies between 0.734% and 11.7%. It appears that MPMN might occur more frequently than can be explained on the basis of random chance. As expected, the incidence of developing MPMN is noted to rise with increasing age. In addition, the preponderance of men with MPMN is caused primarily by the high frequency of prostatic cancer. Current studies and research need to address the potential of older cancer patients being at higher risk of second primaries.