基底细胞样型乳腺癌中CAIX的表达及临床意义

目的 探讨碳酸酐酶IX(carbonic anhydrase IX,CAIX)在基底细胞样型乳腺癌(basal-like breast carcinomas,BLBCs)中的表达,分析其与乳腺癌患者相关临床病理指标的关系.方法 应用免疫组化SP法检测CAIX在45例BLBCs、25例非基底细胞样型乳腺癌(non- basal-like breast carcinomas,non-BLBCs)和10例正常乳腺组织中的表达.结果 免疫组化检测结果显示,CAIX在BLBCs组织中的阳性表达率明显高于non-BLBCs和正常乳腺组织(P<0.05);BLBCs组织中CAIX的表达与肿瘤直径(P=0.001)、pTNM分期(P=0.014)及淋巴结转移(P=0.006)均呈正相关(P<0.05).结论 CAIX在BLBCs中高表达,提示其可能参与该型乳腺癌病程进展的重要分子;CAIX的表达与多项临床病理指标、尤其是淋巴结转移密切相关,提示其可作为预测BLBCs淋巴结转移及预后的指标.     

Clinicopathological characteristic and immuniohistochemical staining of the adenoid cystic carcinoma and basal cell adenoma in salivary gland

目的 观察CK7、Calponin、CD117、Ki-67在涎腺腺样囊性癌(adenoid cystic carcinoma,ACC)和基底细胞腺瘤(basal cell adenoma,BCA)中的免疫表型及其病理组织形态学差异,以提高对该类肿瘤鉴别诊断的认识.方法 对发生于涎腺的26例BCA和17例ACC进行临床和病理组织形态观察并免疫组化标记(CK7、Calponin、CD117、Ki-67).结果 临床特点为两种肿瘤的发病年龄相似,但发生部位不同,ACC好发于腮腺以外的小涎腺,BCA多数发生于腮腺;病理特点为前者表现为浸润性生长并累及周围组织;免疫组化显示两种肿瘤存在免疫表型差异:其中CD117在ACC和BCA之间的强阳性率差异有统计学意义(P<0.05);Ki-67在BCA和ACC之间的强阳性率差异有统计学意义(P<0.01).结论 ACC具有浸润性生长的生物学特征,病理特点上与BCA鉴别主要基于两者的生长方式和组织形态学检查,CD117和Ki-67免疫组化标记有助于其鉴别诊断.     

涎腺腺样囊性癌和基底细胞腺瘤的免疫表型及临床病理特征

目的观察CK7、Calponin、CD117、Ki-67在涎腺腺样囊性癌(adenoid cystic carcinoma,ACC)和基底细胞腺瘤(basal celladenoma,BCA)中的免疫表型及其病理组织形态学差异,以提高对该类肿瘤鉴别诊断的认识。方法对发生于涎腺的26例BCA和17例ACC进行临床和病理组织形态观察并免疫组化标记(CK7、Calponin、CD117、Ki-67)。结果临床特点为两种肿瘤的发病年龄相似,但发生部位不同,ACC好发于腮腺以外的小涎腺,BCA多数发生于腮腺;病理特点为前者表现为浸润性生长并累及周围组织;免疫组化显示两种肿瘤存在免疫表型差异:其中CD117在ACC和BCA之间的强阳性率差异有统计学意义(P<0.05);Ki-67在BCA和ACC之间的强阳性率差异有统计学意义(P<0.01)。结论 ACC具有浸润性生长的生物学特征,病理特点上与BCA鉴别主要基于两者的生长方式和组织形态学检查,CD117和Ki-67免疫组化标记有助于其鉴别诊断。     

肾黏液样小管状和梭形细胞癌的临床病理学分析

目的：探讨肾黏液样小管状和梭形细胞癌（ mucinous tubu1ar and spind1e ce11 carcinoma,MTSCC）的临床病理学特征、免疫表型及鉴别诊断。方法回顾性分析2例MTSCC的临床病理学特征,并复习相关文献。结果 MTSCC临床表现无特异性,CT、MRI等影像学检查可辅助诊断,确诊需依赖病理检查。免疫表型：瘤细胞表达 CK7、CK18、CK19、P504S、EMA、vimentin、CK34βE12、E-cadherin,不表达 CD15、CD10、CD56、Syn、CgA、CD117、C-erbB-2及 vi11in。结论MTSCC是一种罕见的低级别恶性肿瘤,需与集合管癌、乳头状肾细胞癌、肾髓质癌等鉴别,CT、MRI及免疫组化检查有助于诊断。     

肾集合管癌的临床病理分析

目的 观察肾集合管癌的临床病理特点,探讨其病理诊断与鉴别诊断.方法 对2例肾集合管癌的临床特点、病理学检查进行观察,采用免疫组化EnVision法检查CK7、CK19、CK20、34βE12、vimentin、CD10、P504S、E-cadherin的表达.并选择9例Ⅱ型、核分级为Ⅲ级的乳头状肾细胞癌、6例伴广泛肾实质侵犯的肾盂高级别尿路上皮癌与肾集合管癌进行形态学与免疫表型的比较.结果 肾集合管癌占同期上皮性肿瘤的0.66%,血尿为主要临床表现,1例患者术后3月死于肺转移.肿瘤均位于肾髓质,以管状结构为主,伴有肉瘤样分化,广泛侵犯肾实质,间质纤维化及中性粒细胞反应,周围集合管可见异型增生;免疫组化CK19及vimentin( ,2/2)、CK7及34βE12( ,1/2),CK20、CD10、P504S、E-cadherin均阴性.Ⅱ型乳头状肾细胞癌、尿路上皮癌未见集合管上皮异型增生;乳头状肾细胞癌表达vimentin( ,8/9)、CD10及P504S( ,7/9)、CK7( ,3/9)、CK19( ,1/9),34βE12、E-cadherin、CK20均阴性;尿路上皮癌CK7、CK19、34βE12均( ,6/6),E-cadherin( ,5/6),CK20( ,4/6),CD10、p504s、vimentin均阴性.结论 集合管癌是一种少见、高度恶性的肾上皮性肿瘤,形态和免疫表型多样化.灰白色肿块位于髓质、周围集合管上皮异型增生,无肾盂尿路上皮异型增生及原位癌存在可与乳头状肾细胞癌、尿路上皮癌鉴别.CD10、CK19、34βE12、P504S 、E-cadherin的染色有助于鉴别诊断.     

肾黏液样小管状和梭形细胞癌与乳头状肾细胞癌的免疫表型及遗传学改变

目的 研究肾脏黏液样小管状和梭形细胞癌(mucinous tubular and spindle cell carcinoma, MTSCC)及乳头状肾细胞癌(papillary renal cell carcinoma, PRCC)的免疫表型及遗传学特征,探讨它们在肿瘤鉴别诊断中的意义.方法 应用免疫组化方法分别检测7例MTSCC及10例PRCC中 vimentin、RCC、CK7、CK19、34βE12、AMACR、CD10及CD117的表达,同时应用荧光原位杂交(fluorescence in situ hybridization, FISH)技术检测两种肿瘤中7号染色体的遗传学改变.结果 (1) vimentin、RCC、CK7、CK19、AMACR、CD117及34βE12在两种肿瘤中的表达均无明显差别;CD10在50% (5/10例)的PRCC中呈阳性表达,而在MTSCC 中均呈阴性反应.(2) FISH结果显示:10例 PRCC均存在7号染色体三倍体,而在MTSCC中未检测到这一遗传学改变.结论 MTSCC是一种罕见的低级别多形性肿瘤,其某些组织学特征及免疫表型与PRCC相似,极易误诊.7号染色体的异常改变对MTSCC和PRCC的鉴别诊断有着十分重要的意义.     

基底细胞样型乳腺癌中HIF-1α、VEGF的表达及临床意义

目的 观察缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)、血管内皮生长因子(vascular endothelial growth factor,VEGF)在基底细胞样型乳腺癌(basal-like breast carcinomas,BLBCs)中的表达,探讨其与肿瘤侵袭转移的关系及两者之间的相关性.方法 采用免疫组化SP法检测HIF-1α、VEGF在45例BLBCs、25例非基底细胞样型乳腺癌(non-basal-like breast carcinomas,non-BLBCs)和10例正常乳腺组织中的表达.结果 HIF-1α、VEGF在BLBCs组织中的阳性率明显高于non-BLBCs和正常乳腺组织(P<0.05);BLBCs组织中HIF-1α的表达与肿瘤直径、pTNM分期及淋巴结转移均呈正相关关系(P<0.05);VEGF的表达与肿瘤pTNM分期及淋巴结转移相关(P<0.05),并且两者之间有相关性(P=0.028).结论 HIF-1α、VEGF在BLBCs组织中高表达,提示其可能是参与BLBCs病程进展的重要分子;HIF-1α、VEGF的表达与多项临床病理指标,尤其是淋巴结转移密切相关,提示其可作为预测BLBCs淋巴结转移及预后的指标.     

乳腺导管内癌分子分型应用研究

目的 采用免疫组织化学检测方法 对乳腺导管内癌进行分子分型.方法 收集50例乳腺导管内癌存档蜡块,用单克隆抗体CK5/6、CK8、CK18、34βE12、p63、S-100、SMA、CD10、CD117、EGFR、ER、PR和HER2进行免疫组织化学EnVision法染色,按照免疫表型分为5种类型:腺腔A型(ER+/PR+/HER2-)、腺腔B型(ER+/PR+/HER2+)、正常乳腺样型(ER-/PR-/HER2-且不表达基底/肌上皮标记及EGFR)、HER2过表达型(ER-/PR-/HER2+)和基底细胞样型(ER-/PR-/HER2-,且至少表达一种基底型角蛋白和(或)肌上皮标记物或EGFR).结果 腺腔A型16例(32%),腺腔B型19例(38%),HER2过表达型13例(26%),基底细胞样型2例(4%),无正常乳腺型.2例基底细胞样型,均表达CK5/6、CD117,例1同时表达SMA,例2表达CK8、CK18、34βE12、S-100,均为高级别导管内癌.结论 乳腺导管内癌可按免疫表型进行分子分型,部分导管内癌具有与基底细胞样癌相同的免疫表型,可能是基底细胞样癌的前驱病变,其诊断依赖于免疫组化检测.     

乳腺腺样囊性癌18例临床病理分析

目的探讨乳腺腺样囊性癌(adenoid cystic carcinoma of the breast,ACC)的临床病理特征、免疫表型及其鉴别诊断。方法复习18例ACC的临床病理资料,观察肿瘤的组织形态学及免疫表型特点。同时对患者进行随访获取预后信息。结果 18例ACC患者均为女性,年龄29～80岁。肿瘤大体上多界限清楚,镜下呈浸润性生长,主要由筛状、管状-梁索状、实体和微囊结构组成。肿瘤成分包括腺上皮、肌上皮、基底样细胞和细胞外基质。肿瘤的腺上皮成分表达CK7、CK5/6和CD117,肌上皮成分表达SMA和p63,基底样细胞不同程度表达CK5/6、p63和CD117。随访期内有2例患者肿瘤局部复发,无患者死亡。结论 ACC是一组具有形态学异质性的肿瘤,其腺上皮、肌上皮和基底样细胞成分的免疫表型各有特点,联合运用CK7、CK5/6、p63、SMA和CD117有助于诊断与鉴别诊断。ACC预后良好,具有基底样特征的实体型ACC可能是侵袭性更强的组织学亚型。     

乳腺浸润性导管癌中p57kip2、cyclin D1和cyclin E的表达及意义

目的探讨p57kip2、cyclin D1及cyclin E蛋白在乳腺癌发生、发展中作用.方法用免疫组化S-P法检测64例乳腺浸润性导管癌(invasive ductal carcinoma,IDC)、15例乳腺导管原位癌(ductal carcinoma in situ,DCIS)和15例癌旁正常乳腺组织中p57kip2、cyclin D1和cyclin E蛋白的表达情况.结果p57kip2、cyclin D1和cyclin E蛋白在IDC的阳性率与在乳腺不同组织之间相比,cyclin D1、cyclin E蛋白在DCIS的阳性率与癌旁正常乳腺组织之间相比差异均有显著性(P≤0.05,P＜0.01).在IDC中,三者表达均与腋窝淋巴结转移有关(P≤0.05,P＜0.01),cyclin D1蛋白的表达与组织学分级有关(P＜0.01),cyclinE蛋白的表达与肿块大小有关(P＜0.01);p57kip2与cyclin D1之间、p57kip2与cyclin E之间的表达均呈负相关(P＜0.01)、cyclinD1与cyclin E之间的表达呈正相关(P＜0.01).结论p57kip2蛋白低表达、cyclin D1和cyclin E蛋白高表达可能是乳腺组织恶性转变以及乳腺癌发生淋巴结转移的重要生物学标志,cyclin D1和cyclin E蛋白异常表达是乳腺癌发生的早期事件.联合检测p57kip2、cyclin D1及cyclin E蛋白对预测乳腺癌淋巴结转移有重要意义.     

p16INK4a expression in basal-like breast carcinoma

BLBC represents a distinctive group of invasive breast carcinomas with specific genotype and immunopro-file. BLBC is usually defined by gene expression profiling and is currently associated with poor outcome. BLBCs are estrogen receptor (ER) negative, progesterone receptor (PgR) negative, HER2 negative, and usually show a variable expression of basal cytokeratins (CKs), EGFR and CD117. p16 ^INK4a is a tumor suppressor protein, encoded by the CDKN2A gene, which regulates cell cycle. The reported association of abnormalities in the p16/Rb pathway with increased risk of malignancy prompted us to determine the expression of p16^INK4a in a group of BLBC; the results were compared with a group of high-grade invasive carcinoma (HG-IC) of breast. Tissue microarrays (TMA) were constructed in triplicate including 18 BLBC and 18 HG-IC. All BLBC cases were ER-/PgR-/HER2-. Seventeen (94%) BLBC were CK 5/6+/CK 14+; 14 (78%) BLCB showed EGFR expression and 13 (72%) were CD117 positive. BLBCs showed a strong positive reaction with p16 ^INK4a antibody in 16 of 18 (89%) cases. Although the significance of p16 ^INK4a expression in breast cancer is not fully understood, we have shown that p16^INK4a is strongly expressed in breast cancers with basal-like phenotype. Since it is known that p16^INK4a is associated with aggressive behavior in human carcinomas, these data suggest that p16^INK4a play a role in the poor prognosis of BLBC.     

CK5 is more sensitive than CK5/6 in identifying the "basal-like" phenotype of breast carcinoma

Multiple immunohistochemical stains, including cytokeratin (CK)5/6, are used in a panel format to identify "basal-like" carcinomas. We set out to determine the sensitivity and specificity of the CK5 antibody (clone XM26) and compared its expression with that of CK5/6 (clone D5/16B4) in a variety of breast carcinoma cases. The study was performed on 3 breast carcinoma tissue microarrays (TMAs). TMA-1 consisted of 59 consecutive breast carcinoma cases. TMA-2 (n = 16) and TMA-3 (n = 11) consisted of basal-like breast carcinomas previously characterized morphologically and immunohistochemically at our institution. Of the 86 total cases, 20 were positive for CK5 and CK5/6, 14 were positive for CK5 only, and 52 were negative for both. The sensitivity of CK5 for identifying basal-like tumors was 97% compared with 59% for CK5/6. Both antibodies had comparable specificity of more than 95%. For positive cases, the percentage and intensity of staining was much higher with CK5 than with CK5/6 (P = .0001).     

Metaplastic breast carcinomas are basal-like tumours

AIMS: Recently, an immunohistochemical panel comprising antibodies against HER2, oestrogen receptor (ER), epidermal growth factor receptor (EGFR) and cytokeratin (CK) 5/6 was reported to identify basal-like breast carcinomas, as defined by cDNA microarrays. Our aim was to analyse a series of metaplastic breast carcinomas (MBCs) using this panel plus two other basal markers (CK14 and p63) and progesterone receptor (PR), to define how frequently MBCs show a basal-like immunophenotype. METHODS AND RESULTS: Sixty-five cases were retrieved from the pathology archives of the authors' institutions and reviewed by three of the authors. Immunohistochemistry with antibodies for HER2, ER, EGFR, CK5/6, CK14 and p63 was performed according to standard methods. All but six cases (91%) showed the typical immunoprofile of basal-like tumours (ER- and HER2-, EGFR+ and/or CK5/6+). When CK14 and p63 were added to the panel, two additional cases could be classified as basal-like. The majority of MBCs lacked PR, except 4/19 (21%) carcinomas with squamous metaplasia. CONCLUSIONS: Our results demonstrate that MBCs show a basal-like phenotype, regardless of the type of metaplastic elements. Moreover, as these neoplasms frequently overexpress EGFR (57%), patients with MBC may benefit from treatment with anti-EGFR drugs.     

CD10 and HHF35 actin in the differential diagnosis between Collagenous spherulosis and adenoid-cystic carcinoma of the breast

Collagenous Spherulosis (CS) and Adenoid-Cystic Carcinoma (AdCC) of the breast consist of cribriform proliferations of epithelial and myoepithelial cells with an immunophenotypic overlap of some myoepithelial markers, such as p63 and smooth muscle actin (SMA). To our knowledge, CD10 and HHF35 actin have not been assessed in the differential diagnosis of these two breast lesions. We performed an immunohistochemical study on 6 cases of CS and 9 cases of AdCC. We found CD10, muscle-specific actin (HHF35), Estrogen and Progesterone receptors (ER and PR) to be strongly expressed in CS, but not in AdCC; C-kit was diffusely positive in AdCC and scanty in CS; SMA, p63 and Cytokeratine 5/6 (CK5/6) were positive in both. Our results also confirm that AdCC could be true basal-like neoplasia, probably arising from a basal stem line tending to divergent differentiation toward CK5/6/C-kit+, ER/PR-, epithelial basal-like cell type, and toward a myoepitelial-like cell type, with an incomplete SMA/p63+, CD10/HHF35- immunophenotype. By contrast, CS is a reactive, benign proliferation of two well-differentiated cell types: epithelial (ER/PR+, C-kit-) and myoepithelial cells with a complete immunophenotype including CD10/HHF35 positivity. Our study highlights the usefulness of CD10 and HHF35 in the differential diagnosis and helps to understand the histogenesis of the two lesions.     

基底细胞样型浸润性乳腺癌病理形态观察

目的 观察基底细胞样型浸润性乳腺癌的形态特点,为该类型癌的诊断提供依据.方法 收集109例乳腺浸润性导管癌存档蜡块,用单克隆抗体CK56、CK14、CK818、CK34βE12、calponin、p63、CD10、ER、PR和c-erbB-2进行免疫组织化学Max VisionTM法染色,按照免疫表型将本组分为5种类型:腺腔A型(ER+HER2-),腺腔B型(ER+HER2+),正常乳腺样型(ER-HER2-),HER2过表达型和基底细胞样型(至少表达一种基底细胞角蛋白和(或)肌上皮标记物,且ER-HER2-).重点观察基底细胞样型的组织形态表现.结果 腺腔A型48例(44.0%),腺腔B型15例(13.8%),HER2过表达型15例(13.8%),正常乳腺型10例(9.2%),基底细胞样型19例(17.4%).2例除肌上皮标记物外,还同时表达c-erbB-2和(或)ER,组织类型暂未定.在19例基底细胞样型中有16例表达CK56,17例表达CK818,11例表达CK14,18例表达CK34βE12,5例表达p63,6例表达CD10,1例表达calponin.肿瘤直径1.2～7.0 cm(平均3.9 cm);其中＞5 cm者6例.除1例病变以高级别导管内癌为主外,组织学分级为2级者9例,3级者9例,与非基底细胞样型相比3级者显著增多(P＜0.01).基底细胞样型主要组织形态表现包括:13例癌组织呈单纯推挤性(膨胀性)生长,各例边缘均可见到淋巴细胞,18例肿瘤以巢状和(或)片状排列为主,17例核分级为3级,并可见到散在巨核和(或)怪核细胞,7例呈合体细胞样生长,17例有粉刺样坏死,上述形态出现率与非基底细胞样癌比较均显著增多(P＜0.01).结论 基底细胞样型浸润性乳腺癌最有诊断性价值的形态特点是推挤性浸润边缘、周边有显著的淋巴组织、粉刺样坏死、散在巨怪细胞、大巢或片状组织结构和呈合体细胞样生长.     

Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes

DNA microarray profiling studies have led to the classification of invasive breast carcinoma into luminal/estrogen receptor-positive, normal breast-like, Her2/neu-overexpressing, and basal-like types. Among these groups, the basal-like subtype is associated with the poorest clinical outcome in Western countries. To date, the clinicopathologic characteristics of the basal-like carcinomas, compared with other subtypes, have not been described in the Korean population. In this study, we used tissue microarray to examine the expression of basal cytokeratins (CK) (CK5 and CK14) and luminal CK (CK8/18), epidermal growth factor receptor, c-kit, hormone receptors (HRs), p53, and Her2/neu in 776 consecutive patients diagnosed with invasive breast carcinoma from January 1993 to December 1998 and categorized these cases into 5 subgroups (basal-like, HR-expressing, Her2/neu-overexpressing, HR and Her2/neu-expressing, and null subtypes negative for all markers), based on the immunohistochemical data. We identified cases of 114 (14.7%) basal-like, 345 (44.5%) HR-expressing, 133 (17.1%) Her2/neu-overexpressing, 61 (7.8%) HR and Her2/neu-expressing, and 123 (15.9%) null subtypes. Histologically, most basal-like breast cancers were invasive ductal carcinoma, not otherwise specified (98 cases, 86.0%), with high nuclear and/or histologic grades, and most metaplastic carcinomas (6 [75.0%] of 8 cases) were the basal-like subtype. Both basal-like and Her2/neu-overexpressing subtypes were associated with larger tumor sizes (mean, 3.6 and 3.3 cm, respectively) than the HR-expressing group (mean, 2.8 cm) (P = .001 and P = .036, respectively). Nodal stage of Her2/neu-overexpressing subtype was higher than that of basal-like subtype; however, overall stage was not different between the 2 groups (P = .010 and .123, respectively). Distant metastasis was most frequently observed in the Her2/neu-overexpressing subtype (33.8%), which was prognostically the worst subgroup of breast cancers. In contrast to previous findings from Western countries, our analyses reveal that the Her2/neu status is the most important prognostic factor of breast cancers.     

Basal-like breast carcinomas: clinical outcome and response to chemotherapy

BACKGROUND: Grade-III invasive ductal carcinomas of no special type (IDCs-NST) constitute a heterogeneous group of tumours with different clinical behaviour and response to chemotherapy. As many as 25% of all grade-III IDCs-NST are known to harbour a basal-like phenotype, as defined by gene expression profiling or immunohistochemistry for basal cytokeratins. Patients with basal-like breast carcinomas (BLBC) are reported to have a shorter disease-free and overall survival. MATERIAL AND METHODS: A retrospective analysis of 49 patients with BLBC (as defined by basal cytokeratin expression) and 49 controls matched for age, nodal status and grade was carried out. Histological features, immunohistochemical findings for oestrogen receptor (ER), progesterone receptor (PgR) and HER2, and clinical outcome and survival after adjuvant chemotherapy were compared between the two groups. RESULTS: It was more likely for patients with BLBCs to be found negative for ER (p<0.0001), PgR (p<0.0001) and HER2 (p<0.01) than controls. Patients with BLBCs were found to have a significantly higher recurrence rate (p<0.05) and were associated with significantly shorter disease-free and overall survival (both p<0.05). In the group of patients who received anthracycline-based adjuvant chemotherapy (BLBC group, n = 47; controls, n = 49), both disease-free and overall survival were found to be significantly shorter in the BLBC group (p<0.05). CONCLUSIONS: BLBCs are a distinct clinical and pathological entity, characterised by high nuclear grade, lack of hormone receptors and HER2 expression and a more aggressive clinical course. Standard adjuvant chemotherapy seems to be less effective in these tumours and new therapeutic approaches are indicated.