乳腺浸润性微乳头状癌的形态改变与生物学行为的关系

目的 观察乳腺浸润性微乳头状癌的形态与生物学行为之间的关系。方法 对2088例术前没有作活检取材(仅经细胞学或细针穿刺活检诊断)的乳腺癌乳腺切除标本做全乳腺切片检查,其中浸润性导管癌1880例,观察浸润性微乳头状癌的临床病理学特征及光镜、电镜下的形态学表现。结果 浸润性微乳头状癌的发生率为6．2％(117／1880),其淋巴管侵犯(54．7％,58／106)、淋巴结转移阳性率(76．4％,81／106)及转移的个数(平均9．6)均明显的高于浸润性导管癌。光镜下特征性表现为癌巢由呈集块型或(和)腺管型的微乳头状癌巢组成,与网状间质间形成明显的空隙(主间质分离)。电镜下见癌巢与间质接触侧的细胞表面有大量的微绒毛,与间质的结合弱;癌细胞质内含有丰富的细丝;间质内见丰富的脉管。结论 浸润性微乳头状癌的淋巴管侵袭力强和淋巴结转移率高,这种恶性程度高的生物学行为可能与其癌巢的容易脱离及肿瘤细胞本身所具有的高度运动能力以及富含脉管的网状间质有关。     

白细胞介素-1β的表达及间质微血管密度在乳腺浸润性微乳头状癌中的意义

目的 研究白细胞介素(IL)-1β的表达和间质微血管密度在乳腺浸润性微乳头状癌(IMPC)中的意义.方法 采用免疫组织化学LSAB法检测100例IMPC、97例浸润性导管癌(IDC)中IL-1β和CD34的表达并计数微血管密度,比较其差异并分析IMPC中IL-1β、CD34的表达与ER、PR、肿瘤细胞增殖指数Ki-67、组织学分级和淋巴结转移等主要病理学特征的关系.结果 (1)IMPC中IL-1β的表达与IDC差异无统计学意义(P=0.924);(2)IMPC中IL-1β的表达与Ki-67的表达(x2=7.538,P=0.023)、组织学分级(x2=6.556,P=0.038)及淋巴结转移个数(P=0.008)呈正相关,而与ER呈负相关(z=-2.106,P=0.035);(3)微血管密度:IMPC组(66.4±15.9)明显高于IDC组(60.0±14.1,t=2.995,P=0.003),且在IMPC中淋巴结转移组(68.8±13.9)显著高于无淋巴结转移组(54.4±20.7,t=-3.459,P=0.001);IMPC中组织学Ⅱ、Ⅲ级组(68.3±15.0)显著高于I级组(59.9±17.6,t=-2.281,P=0.025),而微血管密度与ER、PR、Ki-67表达无相关性.结论 IL-1β表达增高、间质微血管密度增加可能是促进乳腺IMPC肿瘤细胞增殖和淋巴结转移的关键因素.     

乳腺浸润性微乳头状癌的病理学特征与淋巴结转移的关系

目的研究乳腺浸润性微乳头状癌(IMPC)的病理学特征与淋巴结转移的关系。方法观察51例乳腺IMPC的主要病理学特征及淋巴结转移情况,采用免疫组织化学方法(LSAB法)检测IMPC中血管内皮生长因子(VEGF)-C和VEGF受体(R)-3的表达并计数淋巴管密度,分析其与淋巴结转移的关系。结果(1)乳腺IMPC病理组织学分级Ⅱ、Ⅲ级组的淋巴结转移数平均12.5个,明显高于Ⅰ级组的4.0个;(2)间质淋巴细胞浸润(+)和(++)组的淋巴结转移率(27/28,96.4%)明显高于(-)和(±)组(14/23,60.9%),且其淋巴结转移数平均14.4个,也明显高于(-)和(±)组的4.6个;(3)IMPC肿瘤细胞的VEGF-C表达在病理组织学分级Ⅱ、Ⅲ级组显著高于Ⅰ级组(P=0.03),VEGF-C的表达与淋巴结转移呈正相关(P=0.006);淋巴管密度与VEGF-C表达(P=0.009)、淋巴结转移(P=0.007)呈正相关;(4)肿瘤组织中IMPC成分的多少与淋巴结转移无显著性关系,淋巴结转移灶为纯IMPC或以IMPC成分为主;(5)28例伴有导管原位癌的IMPC中,14例为微乳头状型导管原位癌(14/28,50%)。结论乳腺IMPC的病理组织学分级、淋巴管密度及间质淋巴细胞浸润可能是影响IMPC淋巴结转移的关键性因素。VEGF-C和VEGFR-3表达增高是促使IMPC发生淋巴结转移的重要原因。微乳头状型导管原位癌可能是IMPC的早期阶段。     

前列腺干细胞抗原的表达在乳腺浸润性微乳头状癌中的意义

目的 探讨乳腺浸润性微乳头状癌(IMPC)中前列腺干细胞抗原(PSCA)在蛋白和mRNA水平的表达及其与临床病理特征的关系.方法 采用免疫组织化学(LSAB法)检测66例IMPC、67例非特殊型浸润性导管癌(IDC-NOS)中PSCA的表达,比较其差异并分析PSCA的表达与IMPC临床病理特征之间的关系.采用逆转录聚合酶链反应(RT-PCR)检测10例IMPC和10例IDC-NOS癌组织及其对应的正常乳腺组织中PSCA mRNA的表达水平.结果 免疫组织化学染色结果显示,PSCA在66例IMPC中有47例高表达(71.2%,47/66),67例IDC-NOS中35例高表达(52.2%,35/67),两组表达水平之间的差异具有统计学意义(P=0.024);IMPC中PSCA的表达与淋巴结转移呈正相关(P=0.039).RT-PCR结果显示,PSCA在10例IMPC和10例IDC-NOS癌组织中各有7例和5例表达,且全部高于对应的正常乳腺组织;IMPC癌组织中PSCA表达强度明显高于IDC-NOS癌组织.结论 PSCA的表达可能在IMPC淋巴结转移过程中发挥了重要作用.

Abstract：

Objective To study the expression of prostate stem cell antigen (PSCA) at protein and mRNA levels in invasive micropapillary carcinoma of the breast (IMPC) and to analyze the relationship between PSCA expression and clinicopathologic features. Methods The expression of PSCA protein was analyzed by immunohistochemistry (LSAB) in 66 cases of IMPC and 67 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). The association between PSCA expression and clinicopathologic features was also analyzed in IMPC. Furthermore, RT-PCR was used to detect PSCA mRNA in 10 cases of primary IMPC and 10 cases of primary IDC-NOS with paired normal breast tissues, each from the same subject. Results Immunohistochemical analysis revealed the overexpression of PSCA in 47 of 66 (71.2%) cases of IMPC and 35 of 67 (52.2%) IDC-NOS. Statistical analysis showed a significant difference of PSCA expression between IMPC and IDC-NOS (P=0.024). In IMPC, the expression of PSCA was correlated with lymph nodes metastasis (P=0.039). RT-PCR showed the mRNA level of PSCA was significantly higher in primary IMPC and IDC-NOS tissue than that in paired normal breast tissue (7/10 and 5/10, respectively), and it was also significantly higher in primary IMPC tissue than that in IDC-NOS tissue.Conclusion PSCA might play an important role in lymph node metastasis in IMPC.     

重视乳腺浸润性微乳头状癌的诊断

在2003年10月出版的新版WHO乳腺和女性生殖系肿瘤的病理学与遗传学分类中,增加了一些新的肿瘤类型,浸润性微乳头状癌(invasivemicropapillarycarcinoma,IMPC)就是其中的一种新类型。实际上,IMPC早在1980年就由Fisher等首次报道,当时被称为具有桑葚体样形态学改变的浸润性乳头状癌。直到1993年Siriaunkgul和Tavassoli。才正式提出IMPC的概念,此后有关IMPC的研究陆续报道。鉴于长期以来IMPC一直被认为和被诊断为浸润性导管癌的一种形态学上的亚型,或称之为浸润性导管癌伴微乳头状分化;并且迄今国外对IMPC的诊断标准,临床病理学特征和预后等方面的意见不一,而国内对IMPC还处于初步认识阶段,但IMPC所具有的不可忽视的发病率和预后差的生物学行为,应引起临床及病理医生的高度重视,有必要对IMPC作一强调和评价。     

病理学

0500735 乳腺浸润性微乳头状癌上皮性钙黏附素的表达及意义，0500736 关于乳腺普通性增生、不典型增生和原位癌相互关系及鉴别诊断的探讨，0500737 人精子细胞膜结合型透明质酸酶在乳腺癌的表达及临床病理意义，0500738 石蜡包埋尤文瘤／外周原始神经外胚瘤中EWS—FLI1融合基因的表达，0500739 DARPP-32在胃癌中的表达及其意义。     

Twist转录因子、E-钙黏蛋白和N-钙黏蛋白在乳腺癌中的表达及意义

目的 观察上皮间质转化因子Twist转录因子(简称Twist)和相关蛋白E-和N-钙黏蛋白(cadherin)在乳腺癌中的表达及其与患者临床病理指标的关系.方法 采用免疫组织化学SP法检测56例浸润性导管癌、38例浸润性小叶癌和41例导管内癌以及10例正常乳腺组织中Twist、E-和N-cadherin的表达.结果 (1)三种病理类型乳腺癌组织中,Twist阳性率分别为46.4%(26/56)、79.0%(30/38)和26.8%(11/41),其中浸润性小叶癌中Twist阳性率显著高于浸润性导管癌和导管内癌(分别P=0.002、0.000);E-cadherin阳性率分别为78.6%(44/56)、29.0%(11/38)和80.5%(33/41),其中浸润性导管癌和导管内癌中E-cadherin阳性率显著高于浸润性小叶癌(均P=0.000);N-cadherin阳性率分别为53.6%(30/56)、68.4%(30/56)和31.7%(13/41),其中在浸润性导管癌和浸润性小叶癌中的阳性表达显著高于导管内癌(分别P=0.033、0.001).(2)135例乳腺癌组织中Twist和E-cadherin表达呈显著负相关性(P=0.005,Spearman相关系数-0.239);Twist和N-cadherin 表达呈显著正相关性(P=0.000,Spearman相关系数0.319).(3)乳腺浸润性导管癌差分化组中N-cadherin阳性率显著高于中分化和高分化组(P=0.004).(4)乳腺浸润性小叶癌淋巴结转移组中Twist阳性率显著高于淋巴结未转移组(P=0.037).结论 三种蛋白在三种乳腺癌组织中的表达差异较大.Twist阳性表达与乳腺浸润性小叶癌淋巴结转移相关.N-cadherin阳性率与乳腺浸润性导管癌组织学分级相关.检测这三个指标可为研究乳腺癌的进展和转移机制及评判其生物学行为提供有价值的参考.     

乳腺浸润性微乳头状癌的临床病理特点

乳腺浸润性微乳头状癌（IMPC）因其具有独特的组织形态特点和高度的淋巴管侵犯、淋巴结转移及预后较差的特点,在2003年10月出版的WHO乳腺和女性生殖系肿瘤的病理学与遗传学分类中,作为一种新的肿瘤类型被单列出来。本研究旨在了解乳腺IMPC的临床病理特点。     

伴有神经内分泌分化的乳腺梭形细胞癌

目的探讨乳腺伴有神经内分泌分化的梭形细胞癌的病理形态学和免疫表型特点及鉴别诊断。方法复习2500例乳腺癌切片,找出以梭形细胞占主要优势（〉80％）的癌5例,其中2例梭形细胞型导管内癌和3例梭形细胞型浸润癌。采用HE、阿辛蓝（AB）／PAS和网织染色,以及用癌胚抗原（CEA）、上皮膜抗原（EMA）、细胞角蛋白（CK7、3413E12、AE1／AE3）、神经元特异性烯醇化酶（NSE）、突触素、嗜铬蛋白（cg）A、Lue-7、波形蛋白,S-100、平滑肌肌动蛋白（SMA）、calponin、雌激素受体（ER）、孕激素受体（PR）、c—erbB-2、E-钙黏素、Ki-67、p53抗体进行免疫组织化学观察。其中4例有随访信息。结果患者平均年龄在68岁。镜下：5例癌细胞形态主要为长梭形的上皮样细胞,3例有少数胞质内空泡状细胞,4例可见散在AB阳性细胞。免疫组织化学5例均表达AE1／AE3、EMA、CEA、E-钙黏素和突触素,CK7有4例表达,NSE阳性3例,CgA和Lue7阳性2例,ER阳性4例,PR阳性2例,1例表达c-erbB-2,1例有灶状波形蛋白阳性。免疫组织化学结果显示2例梭形细胞型导管内癌和1例梭形细胞型浸润性癌是梭形细胞型的神经内分泌癌,另外2例梭形细胞型浸润性癌是伴有神经内分泌分化的化生性癌。随访3例存活（24～58个月）,1例27个月内死亡。结论上皮样梭形细胞和细胞内黏液的出现是乳腺伴有神经内分泌分化癌的一个形态学特点。梭形细胞神经内分泌型导管内癌需要和普通导管增生及导管内乳头状瘤鉴别。梭形细胞型的神经内分泌癌和伴神经内分泌分化的梭形细胞浸润性癌需要与梭形细胞肌上皮肿瘤、恶性黑色素瘤及某些软组织肿瘤鉴别。     

浸润性微乳头型尿路上皮癌2例临床病理观察和文献复习

目的 探讨浸润性微乳头型尿路上皮癌的临床病理和免疫组化特征.方法 对2例具有特殊临床病理特征的输尿管和膀胱微乳头型癌作光镜和免疫组化染色观察,结合临床资料进行分析.结果 浸润性微乳头型尿路上皮癌的特殊组织学表现为肿瘤细胞排列成巢状和条索状,位于透明间质空隙内,间质空隙无内皮衬覆.大部分细胞团极向反转,核偏向外侧缘,成"内外倒置"状,极似乳头状结构.免疫组化:该肿瘤表达CK7、CK20、CEA、EMA及E-cadherin.结论 浸润性微乳头型尿路上皮癌为高级别癌,易发生血管和淋巴道转移,预后差.其特殊的形态学变异和免疫组化特点,为其鉴别诊断提供了依据.     

Expression of cell adhesion molecules, CD44s and E-cadherin, and microvessel density in invasive micropapillary carcinoma of the breast

AIMS: Invasive micropapillary carcinoma (IMPC) is a rare variant of ductal carcinoma of the breast and is characterized by high metastatic potential and an aggressive clinical course. This tumour is hence ideal for studying the mechanism underlying tumour biological behaviour, especially metastasis. Cell adhesion molecules, such as CD44 and E-cadherin (Ecad), and angiogenesis are considered important in the invasion and metastasis of tumours. METHODS AND RESULTS: We immunohistochemically analysed 23 IMPCs for expression of a standard form of CD44 (CD44s), Ecad, and CD34 to measure microvessel density (MVD). Results are compared with the changes observed in 23 tubular carcinomas (TCs), another variant of ductal carcinoma that rarely metastasizes. Evaluation of haematoxylin and eosin (H&E) sections showed a higher prevalence of lymph-vascular invasion (19/23, 83%) and regional lymph node involvement (12/15, 80%) in IMPCs; whereas no lymph-vascular invasion or lymph node metastasis was identified in TCs. Loss or reduction of CD44s immunoreactivity was significantly frequent in IMPC (39%) compared with TC (4%) (P = 0.0098), and was associated with positive axillary lymph nodes and lymph-vascular invasion. All cases of IMPC and TC strongly expressed Ecad. MVD (in five 200x fields) was significantly higher in IMPC (88 +/- 37) than in TC (57 +/- 16) (P = 0.001). In the IMPC group, MDV was higher in cases with positive lymph node(s) (P = 0.048), and cases with loss or reduction of CD44s expression (P = 0.011). The same trend was also demonstrated in cases with lymph-vascular invasion (P = 0.077). Moreover, the vessels in IMPC had much smaller calibres with thinner walls than those in TC. CONCLUSIONS: Loss of the CD44 adhesion molecule and high MVD may play a significant role in the high incidence of lymph-vascular permeation and metastasis in IMPC.     

The clinicopathological significance of CD44+/CD24-/low and CD24+ tumor cells in invasive micropapillary carcinoma of the breast

Breast cancer cells with a CD44(+)/CD24(-/low) phenotype have been suggested to have tumor-initiating properties. It is unclear whether their presence correlates with clinicopathological features of invasive micropapillary carcinoma (IMPC) of the breast, an unusual subtype of breast cancer with a high incidence of lymph node metastasis and poor prognosis. CD44 and CD24 expression was determined by double-staining immunohistochemistry in 103 cases of IMPC and in 94 cases of invasive ductal carcinoma (IDC). The prevalence of CD44(+)/CD24(-/low) tumor cells was higher in IMPC than in invasive ductal carcinoma IDC (P=0.018). The CD44(+)/CD24(-/low) tumor cells were also detected in adjacent stroma surrounding the micropapillary structure in 53.4% (55/103) of IMPC, but only in 7.4% (7/94) of stroma of IDC. These tumor cells in stroma of IMPC were positive for vimentin and α-smooth muscle actin, and negative for E-cadherin. The CD44(+)/CD24(-/low) tumor cells in the micropapillary structure of IMPC were associated with those in stroma (P=0.000). Moreover, they were both associated with lymphovascular invasion and extranodal extension, respectively (P<0.05). The proportion of CD24(+) tumor cells was also higher in IMPC than in IDC (P=0.035), and the CD24(+) tumor cells were associated with lymph node metastasis in IMPC (P=0.010). The results suggest that the increased proportion of CD44(+)/CD24(-/low) tumor cells and CD24(+) tumor cells and the epithelial mesenchymal transition may play an important role in aggressiveness and high metastatic risk of breast IMPC.     

Increased expression of SDF-1/CXCR4 is associated with lymph node metastasis of invasive micropapillary carcinoma of the breast

Aims:  Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are implicated in tumour chemotaxis and metastasis. The aim was to examine their roles in the metastasis of invasive micropapillary carcinoma (IMPC) of the breast, a tumour with a high propensity for nodal spread.
Methods and results:  We compared the expression of SDF-1 and CXCR4 in 103 cases of breast cancer containing IMPC components with a control group of 96 cases of invasive ductal carcinoma (IDC), not otherwise specified type by immunohistochemistry and chemical in situ hybridization (CISH). The results showed that the predominant cytoplasmic expression of both SDF-1 and CXCR4 was greater in tumour cells of the IMPC components than in those of the non-IMPC components and the control IDC cases, and was correlated significantly with the number of positive lymph nodes ( P  < 0.05). SDF-1 expression on cell membranes was less frequently identified in IMPC than IDC ( P  = 0.021). Immunohistochemical detection of SDF-1 in endothelial cells of lymphatic vessels was more common in IMPC ( P   =  0.007) and correlated significantly with lymph node status ( P  = 0.002), although SDF-1 mRNA was rarely detected by CISH.
Conclusions:  This study suggests that up-regulation of cytoplasmic expression of SDF-1/CXCR4 might be one of the molecular mechanisms facilitating lymph node metastasis of IMPC.     

Overexpression of TNF-alpha and TNFRII in invasive micropapillary carcinoma of the breast: clinicopathological correlations

Aims: Angiogenesis is essential for tumour growth and metastasis and tumour necrosis factor (TNF)‐α is a potent angiogenic factor. Invasive micropapillary carcinoma of the breast (IMPC), a rare subtype of breast cancer, possesses a lymphotropic nature with a high incidence of lymph node metastasis and poor prognosis. The aim was to evaluate the role of TNF‐α and its receptor TNFRII in the vascular development and metastasis of IMPC. Methods and results: One hundred cases of IMPC and 97 cases of invasive ductal carcinoma, not otherwise specified (IDC) were studied in parallel by immunohistochemistry for TNF‐α and TNFRII, and microvessel density (MVD) of the tumours was measured. The results showed that the expression of TNF‐α and TNFRII and the MVD were higher in IMPC than in IDC (P < 0.05). In IMPC, MVD was significantly increased in those with lymph node metastasis compared with those without nodal metastasis (P = 0.001). TNF‐α expression showed a significant positive correlation with the rate of proliferation, histological grade, lymph node metastasis and MVD (P < 0.05), whereas expression of TNFRII was correlated with TNF‐α expression and the proliferation of tumour cells in IMPC (P < 0.05). Conclusions: Expression of TNF‐α and TNFRII might play an important role in the angiogenesis, tumour cell proliferation and metastasis of IMPC. These markers could represent new targets for therapeutic intervention, i.e. blocking of TNF‐α and its signal transduction could be a promising tool for treatment.     

Loss of membranous E-cadherin expression in pancreatic cancer: Correlation with lymph node metastasis,high grade,and advanced stage

Epithelial cadherin (E-cadherin) is a Ca²⁺-dependent cell-cell adhesion molecule that connects cells via homotypic interactions. Its function is critical in the induction and maintenance of cell polarity and differentiation, and its loss of downregulation is associated with an invasive and poorly differentiated phenotype in colon and other tumours. We have used an avidin-biotin immunoperoxidase technique to localize E-cadherin in microwave-treated, paraffin-embedded sections from 36 patients with pancreatic adenocarcinomas. E-cadherin was expressed by normal ductal and acinar cells with typical membranous staining at the intercellular junctions. Loss of normal surface E-cadherin expression was found in 19/36 (53 per cent) tumours compared to the adjacent normal ductal cells. Abnormal E-cadherin expression was found more frequently in poorly differentiated (grade III) (6/7, 86 per cent) than in well-differentiated tumours (grade I) (4/14, 28 per cent) (P=0·012). Membranous E-cadherin expression was also lost more frequently in primary tumours with lymph node (stage III) (14/23, 61 per cent) and distant metastasis (stage IV) (2/2, 100 per cent) compared with 3/11 (27 per cent) lymph node-negative tumours (stage I) (P=0·043). In conclusions, our data indicate that loss of membranous E-cadherin expression is associated with high grade and advanced stage in pancreatic cancer.     

Correlation between E-cadherin and CD44 adhesion molecules expression and cervical lymph node metastasis in oral tongue SCC: Predictive significance or not

The aim of this article was to evaluate the expression of E-cadherin and CD44 adhesion molecule in oral tongue squamous cell carcinoma (SCC) since inappropriate expression of adhesion molecules raises the metastatic ability of the tumor cells.Biopsy specimens from 92 patients with tongue SCC were examined for the expression of E-cadherin and CD44 by immunohistochemistry. The relationship of immunoreactivity with tumor stage and cervical lymph node metastasis was then analyzed.Sixty-one patients (66.3%) had reduced or negative staining for CD44. Weak or absent staining for E-cadherin was seen in 14 patients (15.21%). Cervical lymph node metastasis is associated with decreased or negative staining for CD44, but no association was found between E-cadherin immunoreactivity and nodal metastasis.Our study reveals that reduced expression of CD44 could be an indicator of high invasiveness of tumor by increasing cervical lymph node metastasis.     

上皮型钙黏素基因启动子甲基化及其mRNA和蛋白表达在鼻咽癌组织中的意义

目的　探讨鼻咽癌癌细胞上皮型钙黏素基因启动子甲基化的程度及其mRNA和蛋白表达水平在鼻咽癌早期浸润和转移中的作用。方法　采用甲基化特异性聚合酶链反应 (methylation specificPCR ,MSP)、蛋白印迹、免疫组织化学和逆转录聚合酶链反应 (RT PCR)等方法检测 2 1例鼻咽癌患者鼻咽原发癌和淋巴结转移癌配对组织中的上皮型钙黏素基因启动子甲基化程度和上皮型钙黏素、β 链接素在不同组织中mRNA和蛋白水平的表达。 结果　 ( 1)在 2 1例鼻咽原发癌组织中 ,11例( 5 2 4% )可以检测到上皮型钙黏素基因启动子的甲基化 ,而在配对的 2 1例淋巴结转移癌组织中 17例 ( 80 9% )则可检测到 ,二者差异具有显著性 (P <0 0 5 )。 ( 2 )在鼻咽原发癌组织中 ,80 %的癌细胞均表达上皮型钙黏素蛋白 ,在淋巴结转移癌组织中只有平均 5 0 %的癌细胞表达 ,两者亦差异有显著性 (P =0 0 0 4) ;但β 链接素蛋白在原发癌和淋巴结转移癌组织中均有较高的表达量 (均为 85 % )。 ( 3 )蛋白印迹检测表明 ,上皮型钙黏素在鼻咽原发癌组织中表达的平均相对强度为 2 0 6 7± 3 2 7,明显高于在转移癌组织中的蛋白平均相对强度 65 0± 15 9;而 β 链接素在不同组织中的蛋白表达相对强度则差异无显著性 (P =0 75 4)。 ( 4)上皮型钙黏