多房囊性肾细胞癌32例临床病理分析

目的：探讨多房囊性肾细胞癌( multilocular cystic renal cell carcinoma, MCRCC)的临床病理特征,提高对该肿瘤的认识。方法复习32例MCRCC的临床资料,观察其病理学形态和免疫表型特征,结合随访资料评价其预后。结果32例中13例位于左肾,18例位于右肾,1例双肾;肿瘤平均最大径4.6 cm(1.0~8.0 cm);男女比为2.2：1。11例行根治性肾全切术,21例行肾部分切除术。肿瘤均为多房囊性,缺少实体成分,囊壁内衬单层(偶为多层或小乳头状)胞质透明或淡粉染、Fuhrman核1级的瘤细胞,腔面富于薄壁血管。瘤细胞表达CK(32/32)、CK7(25/32)、EMA(32/32)、CD10(23/32)、vimentin(20/32),均不表达CD68。术后随访5~140个月,均未见复发和转移,无肿瘤相关死亡病例。结论 MCRCC的瘤细胞核级低、无实性瘤巢;囊壁腔面衬覆胞质透亮或淡粉染细胞伴丰富薄壁血管是诊断线索,免疫表型有助于诊断,患者一般预后良好。     

肝细胞癌8号染色体微卫星变异及其与临床病理特征的关系

目的　探讨肝细胞癌 (HCC)微卫星变异的特点及其与临床病理表现的相关性。方法采用毛细管电泳DNA分析系统 ,对 5 6例HCC中 8号染色体上 10个微卫星的杂合子丢失 (LOH)、微卫星不稳定性 (MSI)和等位基因失衡 (AI) 3种变异特征进行检测。结果　 5 6例HCC在 8号染色体上 10个基因位点发生LOH的总频率为 6 6 1% (37/ 5 6 ) ,LOH以D8S2 6 1最高为 5 3 5 % (2 3/ 4 3) ,其次为D8S172 1(5 2 5 % )和D8S1771(5 2 5 % )。D8S2 77基因位点 ,血清HBsAg阳性患者的LOH频率显著高于HBsAg阴性者 (P <0 0 1) ,D8S2 6 1、D8S2 98和D8S1733基因位点 ,血清HBsAg阴性患者的LOH频率显著高于HBsAg阳性者 (P <0 0 1) ;D8S2 98和D8S1771基因位点 ,直径 >3cm肿瘤的LOH率明显高于≤ 3cm组 (P <0 0 5和P <0 0 1) ;在D8S172 1基因位点 ,无包膜或包膜不完整的肿瘤的LOH显著高于包膜完整的肿瘤 (P <0 0 1) ;D8S2 98和D8S1771基因位点 ,肝内转移者的LOH明显高于无肝内转移者 (P <0 0 5 )。MSI的频率为 12 5 % (7/ 5 6 ) ,AI的频率为 19 6 % (11/ 5 6 )。结论HCC在 8号染色体上存在广泛的微卫星变异 ,其中LOH方式在HCC的发生和发展过程中起重要作用 ,MSI的作用次之。特定基因位点的LOH与临床和病理学参数有一定的相关性     

头颈部鳞癌的微卫星不稳定性和杂合性丢失的初步研究

目的:探讨头颈部鳞癌的微卫星不稳定性(MSI)及杂合性丢失(LOH)。方法:选择来自3、5、6、8、9、13、17和18号染色体的15个微卫星标志对36例头颈部鳞癌标本和相应的外周血进行微卫星分析。结果:36例头颈部鳞癌中,27.8%(10/36)分别有1-8个位点存在MSI,MSI发生率较高的位点为:D17S520(22.9%)、D6S105(16.7%)和D8S264(13.9%)。在9p21-p22和3p14等处存在一定的LOH。微卫星异常的检出率与肿瘤分期、分级无相关性。结论:提示MSI是头颈部鳞癌中较为常见的遗传学变化,染色体9p21-p22和3p14区域可能存在与头颈部鳞癌有关的抑癌基因。     

青少年肾细胞癌的临床病理及分子遗传学研究

目的 探讨青少年肾细胞癌的临床病理特征、遗传学改变、鉴别诊断及预后.方法 对46例青少年肾细胞癌进行光镜观察及免疫组织化学染色,随访并复习相关文献.对46例肿瘤进行von Hippel-Lindau(VHL)基因区域杂合性缺失(LOH)及VHL基因突变筛查.结果 共诊断19例Xp11.2易位/TFE3基因融合相关性肾癌(Xp11 RCC)、9例透明细胞癌、17例乳头状肾细胞癌(PRCC)和1例不能分类肾细胞癌.19例Xp11 RCC均TFE3阳性,而TFEB阴性.8例肿瘤具有巢状和乳头状结构形态类似t(X;17)ASPL-TFE3型肾癌,6例肿瘤组织学类似t(X;1)PRCC-TFE3型肾癌,4例肿瘤形态像透明细胞癌,1例肿瘤组织学形态文献中未被检索到,表现为细胞核呈毛玻璃样,核仁不明显,可见核沟,肿瘤间质见大量黏液.LOH及VHL突变检测结果显示,仅1例透明细胞癌和1例2型PRCC存在LOH,并且该2型PRCC的VHL基因的一个剪切位点存在胚系突变,553+5 G→C.其余45例均未检测出VHL突变.统计学分析表明TFE3阳性肾细胞癌比TFE3阴性肾细胞癌更倾向于高病理分期(pT3/pT4),并且预后较差(P=0.035).结论 青少年肾细胞癌表现出不同的组织学形态以及分子遗传学背景.其中Xp11 RCC为最常见的肾癌亚型.TFE3阳性肾细胞癌的预后要差于TFE3阴性肾细胞癌.     

多囊性肾细胞癌

多囊性肾细胞癌（MCRCC），也叫多囊性透明细胞肾细胞癌（RCC）和多囊性透明细胞癌，是一种预后较佳的少见的肾脏囊性肿瘤。2004年WHO肾肿瘤分类中将MCRCC作为透明细胞肾细胞癌的一种罕见亚型，其预后较佳。虽然文献报道囊性肾细胞癌比实体型透明细胞RCC预后好，但对于诊断MCRCC真正的临床意义和其预后还不清楚。作者根据WHO2004年的诊断标准收集了45例MCRCC，年龄30～80岁，平均54．3岁。男性28例，年龄36～80岁，平均56．3岁；女性17例，年龄30～78岁，平均51．1岁。50％的患者年龄小于50岁。肿瘤直径1—14cm，平均4．9cm，     

多房囊性肾细胞癌18例临床病理分析

目的：探讨多房囊性肾细胞癌（ mu1ti1ocu1ar cystic rena1 ce11 carcinoma,MCRCC）的临床病理学特征、诊断及鉴别诊断。方法回顾性分析18例MCRCC的临床病理学及免疫表型特征,并复习相关文献。结果18例中男性12例,女性6例,年龄26~68岁（平均55.6岁）。影像学检查均示多囊性占位,边界清楚。眼观：肿瘤切面见大小不等的多房囊腔,内含浆液性或血性液体。镜检：肿瘤囊内壁被覆单层透明细胞、复层上皮或上皮缺如,囊内成分大部分流失,纤维性囊壁或囊腔间隔中见灶状透明细胞,呈Ⅰ级细胞核,其为形态学诊断线索。免疫表型：透明细胞CD10、vimentin、EMA均阳性,Ki-67增殖指数低。18例患者平均随访43个月,均无复发或转移,预后良好。结论 MCRCC是一种罕见的肾细胞癌组织学亚型,预后良好,需与肾透明细胞癌囊性变及良性肾囊性病变相鉴别。     

乳腺癌和导管增生病变与1p染色体不稳定的关系

目的检测乳腺普通型导管增生(usual dutal hyperplasia,UDH)、乳腺不典型增生(atypical dutal hyperplasia,ADH)、乳腺导管原位癌(dutal carcinoma in situ,DCIS)及乳腺浸润性导管癌(invasive dutal carcinoma,IDC)中染色体1p微卫星杂合性缺失(loss of heterozygosity,LOH)/微卫星不稳定(microsatellite instability,MSI)的改变规律,探讨乳腺导管增生病变进展为IDC的遗传学改变特征。方法应用PCR法检测20例UDH、7例ADH、25例DCIS、25例IDC石蜡包埋组织,8%尿素变性聚丙烯酰胺凝胶电泳后银染检测染色体1p区间微卫星位点D1S193、D1S463、D1S2881、D1S2885、D1S234、D1S252的LOH/MSI。结果染色体1p的每个位点均发生LOH/MSI,其发生的频率UDH为55.0%、ADH为42.9%、DCIS为64.0%、IDC为72.0%,各组间差异无显著性(P0.05);微卫星位点D1S193、D1S2881、D1S2885、D1S252、D1S234在各组中LOH/MSI的频率差异均无显著性(P0.05)。D1S463的频率在UDH组为5.0%、ADH组为0、DCIS组为45.0%、IDC组为40.0%,其中UDH组与ADH组明显低于DCIS组、IDC组(P0.008)。结论 1p染色体遗传学不稳定是乳腺癌发生的早期事件,D1S463位点的改变可能在乳腺导管增生性病变进展为乳腺癌中起关键作用。     

神经鞘瘤D22S268杂合缺失与组织学类型的相关性研究

目的　探讨神经鞘瘤组织学类型与NF2基因微卫星标记D2 2S2 6 8杂合性缺失 (LOH)的相关性。方法　选择与NF2基因密切相关的微卫星标记D2 2S2 6 8,应用PCR方法检测 35例神经鞘瘤患者的新鲜肿瘤组织标本。结果　病理分型为AntoniA型 2 0例 ,其中LOH 15例 ;AntoniB型 15例 ,LOH 0例。两种病理分型中D2 2S2 6 8LOH发生率存在着显著差异 (P <0 .0 1)。结论　NF2基因的LOH可能在AntoniA型的神经鞘瘤发生过程中起决定性作用。     

肾混合性上皮间质肿瘤和成人囊性肾瘤的临床病理学观察

目的 探讨肾混合性上皮间质肿瘤(MEST)和成人囊性肾瘤的临床病理学特点、免疫表型和鉴别诊断.方法 通过HE和免疫组织化学染色(EnVision法)分析5例MEST和4例囊性肾瘤,并复习有关文献.结果 5例MEST均为女性,中位年龄45岁;囊性肾瘤中男性3例,女性1例,中位年龄41岁;临床表现为腰痛或血尿.大体观察:MEST界清无包膜,切面未见明显出血坏死,其中3例旱实性,1例呈囊实性,另1例呈多囊性其间为厚的纤维分隔;囊性肾瘤有包膜,切面呈多囊性,囊壁薄,无实区和坏死厌.镜下观察:MEST由不等量增生、囊性扩张的腺上皮与不同排列方式的梭形间质细胞混合组成,两种细胞成分无明显异形,2例局部衬覆子宫内膜样或输卵管样上皮;囊性肾瘤为多房囊腔组织,囊壁薄,内衬单层上皮.免疫表型:9例上皮细胞CKpan、上皮细胞膜抗原(EMA)均呈阳性表达;MEST间质梭形细胞波形蛋白(5/5)、平滑肌肌动蛋白(SMA,3/5)、结蛋白(4/5)、CD10(5/5)、ER(4/5)和PR(4/5)呈阳性表达,HMB45、CD34、CD117和S-100蛋白呈阴性;囊性肾瘤间质成分波形蛋白(4/4)、SMA(4/4)、结蛋白(1/4)阳性,ER(3/4)和PR(1/4)少量细胞阳性,CDIO、HMB45、CD34、CDll7和S-100蛋白呈阴性.结论 (1)MEST和囊性肾瘤均是少见的肾脏肿瘤,大多为良性.(2)MEST间叶细胞呈不同程度的平滑肌或肌纤维母细胞分化;2例有MaUerian管上皮分化特征.(3)MEST和成人囊性肾瘤在形态学和免疫表型上有很多相似性,可能为位于同一肿瘤谱系两端的肿瘤.     

肾肿瘤中受体酪氨酸激酶RON的表达及意义

目的 探讨RON在肾肿瘤中的表达以及RON表达与肾肿瘤局部侵袭和分化程度的关系.方法 利用免疫组化法测定48例肾透明细胞癌、20例嫌色细胞癌、3例嗜酸性细胞腺瘤肿瘤组织RON表达.结果 RON在肾嫌色细胞癌中表达强度最高,透明细胞癌其次,而在嗜酸性细胞腺瘤中最低,但无统计学意义差异;透明细胞Fuhrman核分级3-4级阳性表达强度高于核分级1或2级(P<0.05);肿瘤直径>7 cm的RON表达强度大于<7 cm病例;RON在存在.肾盂侵袭的病例中有较高表达的趋势.结论 RON肾细胞癌的演进中可能起重要作用.     

内源性端粒酶抑制基因遗传不稳定性与胃癌进展的关系

目的 研究8号染色体上D8S277位点的杂合性缺失(LOH)和微卫星不稳定性(MSI)对内源性端粒酶抑制基因(PINX1)蛋白表达的影响,阐明PINX1基因遗传不稳定性与胃癌进展的关系. 方法采用石蜡包埋组织抽提DNA,聚合酶链-单链构象多态性(PCR-SSCP)分析,常规银染检测D8S277位点的LOH和MSI,采用Envision免疫组织化学染色和Leica-Qwin计算机图像分析等方法. 结果 D8S277位点的LOH发生率在淋巴结转移组(21.15%)明显高于无淋巴结转移组(0,P<0.05);在胃癌TNM Ⅲ Ⅳ期(24.39%)显著高于Ⅰ Ⅱ期(3.33%,P<0.05).PINX1蛋白阳性率在无淋巴结转移组(78.95%)明显高于有淋巴结转移组(48.08%,P<0.05);TNM分期Ⅰ Ⅱ期(73.33%)明显高于Ⅲ Ⅳ期(43.90%,P<0.05);蛋白表达阴性组LOH阳性率为32.28%,明显高于蛋白阳性组的2.50%(P<0.01). 结论 PINX1基因的遗传不稳定性可能导致该抑癌基因突变,是肿瘤发生发展的一个因素,LOH和MSI通过不同的途径调控胃癌的发生和发展.     

Abnormalities of chromosome 17 in oesophageal cancer

BACKGROUND: Oesophageal cancer is the most common malignancy encountered in South African males, especially in the Eastern Cape and surrounding region of South Africa. There are a number of risk factors and predisposing conditions that have been implicated in the aetiology of the disease. The tylosis oesophageal cancer (TOC) gene, localised to a small region on chromosome 17q25, has been shown to be associated with oesophageal squamous cell carcinoma. AIM: To investigate loss of heterozygosity (LOH) and microsatellite instability (MSI) in the region of the TOC locus. METHODS: In 74 oesophagectomy specimens for squamous cell carcinoma, microsatellite PCR was performed using five fluorescently labelled TOC markers. The PCR products were analysed and the data correlated with clinicopathological findings. RESULTS: LOH ranged from 25% to 60%. LOH for the individual markers was as follows: D17S1839, 25%; D17S1864, 36%; D17S1817, 38%; D17S785, 47.8%; and D17S579, 60%. MSI ranged from 4.1% to 6.8% for the five loci in the 17q region. MSI was 4.1% for the markers D17S579, D17S785 and D17S1817. Marker D17S1864 showed MSI to occur in 4 cases (5.4%) and marker D17S1839 in 5 cases (6.8%). CONCLUSION: No significant relationship between genetic and clinical parameters was observed; however, aberrations in poorly differentiated tumours were high for markers D17S579 and D17S1864 (25% and 37%, respectively), indicating that these markers may have an underlying role in the molecular pathogenesis of oesophageal squamous cell carcinoma. In addition, 63% of patients who died showed LOH for the markers D17S579, D17S1864 and D17S1817.     

Allelic alterations in nontumorous liver tissues and corresponding hepatocellular carcinomas from chinese patients

Allelic imbalance may play an important in tumor progression in hepatocarcinogenesis, but the genetic background of the corresponding nontumorous liver in hepatocellular carcinoma (HCC) is not well defined. We studied the incidence of loss of heterozygosity (LOH) and microsatellite instability (MSI) by microsatellite analysis in both nontumorous livers and the corresponding tumors, by comparing them with the normal DNA from Chinese patients with resected primary HCCs. We also evaluated the pathologic significance of the alterations. We used 18 highly polymorphic microsatellite markers on chromosomes 1, 3, 4, 7, 8, 9, 13, 16, 17, and 18. Our results showed that 70.6% (24 of 34) of the HCCs exhibited LOH at 1 or more loci, and that the overall fractional allelic loss (FAL) was 0.169. MSI was observed in only 1 tumor. In contrast, the nontumorous livers of the HCCs showed a very low incidence of LOH, with only a single LOH detected in 1 of 34 (2.9%) of the nontumorous livers, with an overall FAL index of 0.005. Tumors with LOH at 1 or more loci had significantly more frequent venous invasion (P = 0.019). Allelic loss at locus D9S199 (9p23) was seen more frequently in larger tumors (P = 0.031), and, less significantly, allelic loss at locus D16S516 (16q24.1) was seen more frequently in larger tumors (P = 0.059). LOH was common in predominantly hepatitis B virus-associated HCCs from Chinese patients. However, LOH or MSI in the corresponding cirrhotic or noncirrhotic livers was uncommon.     

Frequent microsatellite alterations in a predominantly younger age of onset breast cancer population

Microsatellite instability (MSI) and loss of heterozygosity (LOH) was investigated in paired tumour and normal tissue DNA from 108 predominantly premenopausal breast cancer patients (under age 45 years at presentation) for 25 simple repeat loci interspersed across 11 chromosomes. MSI was observed at a single locus in 69 (64%) patients; 41 of these had instability at more than one site. Greatest frequency of MSI was at loci D2S1356 (33%), D2S2739 (22%), D3S1766 (21%) and D13S796 (20%). LOH was seen at a single site in 55% of patients and at two or more sites in 27 patients with greatest frequency at D2S1356 (33%), D2S443 (19%) and D17S1299 (18%). Both mutations were found in the same patient but at different loci. Clearly, choice of loci is a determining factor in assessing genomic instability. The relatively high frequency of MSI may also reflect peculiarities of this younger patient population. Occurrence of MSI or LOH was unrelated to clinical stage, nodal status, tumour size or grade or steroid receptor status. It was independent of mutations detected in exons 5-9 of the p53 gene. There was no significant association with survival. The lack of such correlations reflects a random disabling mechanism that may equally affect genes promoting cell death as well as growth.     

Patterns of allelic loss at the BRCA1 locus in Arabic women with breast cancer

Loss of heterozygosity (LOH) of BRCA1, a tumor suppressor gene, is one mechanism of genetic inactivation in both sporadic and familial forms of breast cancer. Studies reported in breast cancers from women of Northern European descent have shown LOH in 30-50% of sporadic tumors. Microsatellite instability (MSI) has served as evidence for involvement of DNA repair genes. This study investigates the extent of allelic imbalance at the BRCA1 region in Arabic women with breast cancer. Paired normal and tumor tissue were available for DNA analysis in 13 cases. Results using fluorescent tagged primers to microsatellite markers D17S1323, D17S1325 and D17S855 intragenic to BRCA1 were analyzed using an ABI 310 DNA sequencer. As compared to normal DNA, MSI and LOH were recognized as a gain and a loss, respectively, of one signal in one allele in the tumor DNA. Microsatellite analyses showed 12 of 13 (92%) cases with LOH or MSI or both. Three cases demonstrated LOH alone, 3 cases with MSI alone. Six cases indicated both LOH and MSI; 2 cases with either LOH or MSI in separate markers. The combined finding of LOH and MSI in the same marker was detected only with D17S1325 in 4/6 cases. The proportion of aberrant findings of the BRCA1 locus in breast cancer appears to be higher in Arabic women than in other populations studied to date.     

原发性胃癌中19p部分微卫星多态位点杂合性缺失分析

目的 筛选胃癌19p部分微卫星多态位点的杂合性缺失（loss of heterozygosite,LOH)频率,以初步确定19p上与胃癌相关基因连锁最密切的微卫星多态位点。方法 采用聚合酶链反应-单链长度多态（polymerase chain reaction-single strand length polymorophism,PCR-SSLP)-银染法选取19p上9对微卫星多态标记（D19S424,D19S216,D19S406,D19S413。D19S221,D19S226,D19S411,D19S883,D19S886）,对43例原发性胃癌的杂合性缺失情况进行了分析。结果 43例中22例至少在1个位点发生LOH,总缺失率为48.88%,这9个位点的LOH频率分别为29.63%,11.53%,33.33%,8.57%,13.15%,8.00%,6.45%,6.89%,10.71%,在D19S886也同时出现微卫星不稳定性（microsatellite instability,MSI)17.85%。结论 提示19p上的LOH缺失频发区域可能涉及与人类原发性胃癌发生发展相关基因的存在。     

Mutation at chromosome 11q23 in human non-familial breast cancer: A microdissection microsatellite analysis

Allelotypic evaluation of loss of heterozygosity (LOH) has been instrumental in the identification of tumour suppressor genes. Here we report a high incidence of LOH at chromosome 11q23 in non-familial breast cancers with in situ, invasive, and metastatic tumour cells microdissected from archival haematoxylin and eosin (H & E) sections for polymerase chain reaction (PCR)-LOH analysis at polymorphic microsatellite loci. Ninety-four cases of non-familial breast cancer were examined at the D11S29 microsatellite locus on chromosome 11q23. Eighty-three cases (88 per cent) were informative and 35 cases overall (42 per cent) had LOH at this locus, comprising 23 per cent of in situ, 36 per cent of invasive, and 28 per cent of metastatic cancers. The DNA from those cancer cells with LOH was amplified at microsatellite loci D11S554 (11p12–p11.2) and D11S534 (11q13). In 19 of 67 cases overall (28 per cent), LOH occurred solely at 11q23. There was an association between LOH at 11q23 and tumour size ≥2 cm (P<0.01) in the overall results and the invasive cancers. The data revealed heterogeneity for LOH at D11S29 in in situ, invasive, and metastatic cells from the same case. In general, however, there was concordance between LOH (or its absence) in in situ and invasive disease. We conclude that the distal part of the long arm of chromosome 11 contains a region involved in breast carcinogenesis and that there is molecular heterogeneity at this chromosomal region in individual breast cancer cells.     

中国人肝癌分泌型卷曲相关蛋白1基因遗传的不稳定性

目的 研究8号染色体上D8S532位点的杂合性缺失(LOH)和微卫星不稳定性(MSI)对分泌型卷曲相关蛋白1基因(sFRP1)蛋白表达的影响,阐明 sFRP1 基因遗传不稳定性与肝癌进展的关系,为揭示sFRP1 基因作用机制和肿瘤发生发展机制提供实验依据. 方法 采用石蜡包埋组织抽提DNA,聚合酶链-单链构象多态性(PCR-SSCP)分析,常规银染检测D8S532位点的LOH和MSI,采用Envision免疫组织化学染色,Leica-Qwin计算机图像分析系统采图和Image-Pro P1uS(IPP)Version5.0专业图像分析软件分析蛋白表达. 结果 在36例肝癌中,D8S532位点LOH和MSI检出率分别为11.11%(4/36)和8.33%(3/36),D8S532位点MSI发生率在60岁以上年龄组(≥60) 26.67%(4/15),高于60岁以下年龄组(<60)0.00%(0/21, P <0.05).相比较于正常组织,86.11%(31/36)的sFRP1蛋白有不同程度表达下降,在肝癌组织中,sFRP1表达阳性率为52.78%(19/36),蛋白表达阴性组LOH阳性率为23.53%(4/17),明显高于蛋白阳性组的0.00%(0/19)( P <0.05). 结论 在中国人肝癌发生进展中,sFRP1蛋白表达下降甚至缺失是普遍现象, sFRP1 基因的遗传不稳定性可能是导致该抑癌基因突变、肿瘤发生的一个机制,LOH在sFRP1表达缺失的过程中起了重要作用.