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.     

基底细胞样型乳腺癌的临床病理观察

目的 观察基底细胞样型乳腺癌(BLBC)的临床病理特征.方法 采用ER、PR、HER2、Ki-67、CK5/6、CK14和表皮生长因子受体(EGFR)进行免疫组织化学EnVision法检测458例女性浸润性乳腺癌以筛选BLBC,比较BLBC与其他免疫表型乳腺癌的临床病理特征.对其中228例浸润性乳腺癌患者进行了随访.结果 458例浸润性乳腺癌中发现BLBC 46例(10.0%).癌灶直径平均3.3 cm.58.7%(27/46)出现推挤性生长方式,52.2%(24/46)出现地图状坏死,30.4%(14/46)癌灶中心出现无细胞纤维化区域以及63.0%(29/46)癌灶周边和间质内有不同程度淋巴细胞浸润.癌细胞异型性明显,核分裂象多见,主要排列成不规则、紧密实性结构.Ki-67高表达(>25%)在BLBC中占43.5%(20/46).CK5/6、CK14和EGFR阳性分别见于58.7%(27/46)、43.5%(20/46)和65.2%(30/46)的BLBC病例.BLBC的3年累积生存率为66.9%,低于管腔A型乳腺癌,与HER2高表达型乳腺癌差异无统计学意义.结论 BLBC在女性浸润性乳腺癌中所占比例为10%,其组织结构和细胞形态具有一定特征性,但诊断BLBC仍必需结合其免疫表型.BLBC是预后比较差的乳腺癌亚型之一.     

乳腺癌分子亚型中BRCA1的表达及其与雌激素受体的关系

目的 研究BRCA1在乳腺癌分子亚型中表达特点及其与雌激素受体的关系.方法 1 452例乳腺癌标本制作组织芯片,免疫组织化学MaxVision快捷法检测ER、PR、HER2、CK5/6、EGFR的表达,按照Nielsen标准进行分子分型.免疫组织化学MaxVision快捷法检测BRCA1的表达水平.结果 腺腔A型,腺腔B型,基底样型,HER2过表达型和裸表达型分别为428例、56例、223例、188例、416例.BRCA1在腺腔A型,腺腔B型,基底样型,HER2过表达型,裸表达型中的表达率分别86.9%(358/412), 87.5%(49/56), 63.0%(136/216), 70.4%(131/186), 60.4%(246/407).BRCA1在基底样型乳腺癌、HER2过表达型和裸表达型中的表达率低于ER阳性乳腺癌腺腔A型(P<0.001)和腺腔B型(P<0.001),BRCA1的阳性表达与ER的阳性表达相关(P<0.001).结论 BRCA1在基底样型乳腺癌和其他ER阴性乳腺癌亚型中的表达下调,其功能异常可能参与ER阴性乳腺癌分子亚型的发生.     

基底细胞样型乳腺癌的临床病理特点和预后意义

目的 探讨中国乳腺癌人群中基底细胞样型乳腺癌(BLBC)的流行病学、临床病理特征和预后意义.方法 采用组织芯片、免疫组织化学和形态学分析等方法将1311例浸润性乳腺癌组织标本分为腺腔A型、腺腔B型、BLBC型、HER2型和不表达型,并分析BLBC的流行病学、临床病理特点.获得随访资料523例,随访2-132个月,平均65.8个月.结果 BLBC发病率17.0%(223/1311),HER2型和不表达型的发病年龄均显著低于腺腔A型,肿瘤直径显著高于腺腔A型.组织结构上,BLBC多为组织学3级,较HER2型和腺腔A型更多见瘤细胞弥漫片状分布和带状分布于坏死周围的特点;多见大块地图状坏死和中央瘢痕、推进性边缘、肿瘤内淋巴细胞浸润和高核分裂指数;细胞形态上,合体细胞和基底样细胞、鳞状细胞化生和梭形细胞化生多见于BLBC.BLBC的复发率显著高于腺腔A型和HER2型,淋巴结转移率显著低于HER2型和不表达型;其他ER阴性乳腺癌(HER2型、不表达型)之无病生存率和总生存率均显著低于腺腔A型;Cox多因素风险模型分析显示基底细胞样标记不是乳腺癌独立预后因素.结论 BLBC在中国乳腺癌人群中的发病率与大多数国外文献报道相似.该亚型乳腺癌既具有不同于非BLBC的、独特的临床病理特点,也具有与其他ER阴性乳腺癌相同的临床病理特点;其形态学上的诸多特征虽不十分特异,但可作为诊断线索提示病理医师结合免疫组织化学等检查做出正确诊断.与腺腔A型相比,BLBC与其他ER阴性乳腺癌具有较差的预后.     

浸润性乳腺癌术前FNA近似分子分型的临床意义

目的探讨浸润性乳腺癌术前细针吸取细胞学(fine needle aspiration,FNA)近似分子分型的可行性及临床意义。方法对42例女性原发性乳腺癌患者术前行细针穿刺术,涂片后进行细胞学诊断。利用免疫细胞化学技术检测ER、PR、HER2、CK5/6和EGFR表达情况,将乳腺癌近似分为腺腔A型(Luminal A)、腺腔B型(Luminal B)、纯HER2过表达型(pure HER2-overexpressing)、基底样型(basal-like)、HER2过表达基底样型(basal-HER2)及正常乳腺型(null)6个分子亚型。将其与术后对应标本的病理学及免疫组化结果进行比较。结果术前穿刺涂片诊断为"高度可疑乳腺癌"及"乳腺癌"的42例女性患者,经术后病理组织学证实均为浸润性乳腺癌,细胞学诊断准确率为100%。在42例乳腺癌细针吸取细胞涂片上利用免疫细胞化学进行术前各分子标记的检测,其中ER/PR阳性率为52.38%(22/42),HER2阳性率为42.86%(18/42),EGFR/CK5/6阳性率为19.04%(8/42)。相对应的石蜡切片经免疫组化检测,ER/PR阳性率分别为52.38%(22/42),HER2阳性率为40.48%(17/42),EGFR/CK5/6阳性率为23.81%(10/42)。其中,1例细胞涂片HER-2为阳性,而对应的石蜡切片为阴性;2例石蜡切片EGFR为阳性,而对应的细胞涂片为阴性,两种方法差异无统计学意义(P>0.05)。结论 FNA是术前诊断乳腺癌准确、易行的方法之一。浸润性乳腺癌术前FNA近似分子分型简单明了,切实可行。其有助于术前掌握乳腺癌的生物学特征,可能成为指导术前新辅助化疗、术式选择的有用指标。     

乳腺癌上皮间质转化与基底细胞样表型的关系

目的 评价乳腺癌七皮间质转化(EMT)与基底细胞样型乳腺癌(BLBC)的关系.方法 依据免疫表型从458例浸润性乳腺癌中筛选出基底细胞样型、管腔A型、管腔B型和HER2过表达型共382例.免疫组织化学EnVision二步法检测FOXC-2、波形蛋白、Syndecan-1和E-cadherin在乳腺癌中表达,并分析其与BLBC的关系.结果 41例BLBC中癌细胞FOXC-2、波形蛋白和Syndecan-1的阳性率以及E-cadherin表达减弱率分别为34.1%(14/41)、43.9%(18/41)、87.7%(36/41)和63.4%(26/41).BLBC的FOXC-2和波形蛋白阳性率均高于其他亚型乳腺癌,其E-cadherin表达较其他亚型乳腺癌下降(P<0.01).BLBC肿瘤间质细胞Syndecan-1阳性率为41.5%(17/41),高于其他亚型乳腺癌(P=0.007).癌细胞FOXC-2表达与波形蛋白表达呈正相关(r=0.607,P<0.01).FOXC-2和波形蛋白阳性组腋窝淋巴结转移率分别为71.4%和66.7%,分别高于阴性组(P=0.002和P=0.001).结论 本结果显示乳腺癌中EMT与BLBC关系最密切.EMT可能是造成BLBC与其他亚型乳腺癌生物学行为差异的蕈要原因.     

乳腺癌原发灶与复发/转移灶HER2低表达状态变化

目的探讨乳腺癌原发灶与复发/转移灶HER2阴性患者中HER2低表达状态的变化及临床意义。方法收集河北医科大学第四医院2015年1月至2022年1月出现复发/转移且原发灶肿瘤HER2阴性的259例乳腺癌患者资料及存档切片, 以免疫组织化学(IHC)染色法确定原发灶及复发/转移灶HER2状态, 其中IHC 2+患者均行荧光原位杂交(FISH)法进一步明确HER2状态, 将HER2 IHC 0判定为HER2-0组, IHC 1+及IHC 2+且FISH无扩增患者判定为HER2低表达组, IHC 3+及IHC 2+且FISH扩增为HER2阳性组, 并对患者进行随访。对比乳腺癌原发灶与复发/转移灶中HER2低表达患者HER2状态的变化, 并分析其临床病理特征及预后。结果乳腺癌原发灶与复发/转移灶HER2状态总体一致率60.6%(157/259, κ=0.178), 共102例(102/259, 39.4%)患者原发灶和复发/转移灶HER2状态不一致, 其中56例(56/259, 21.6%)患者原发灶HER2低表达, 复发/转移灶为HER2-0, 37例(37/259, 14.3%)患者原发灶H...     

中央坏死性乳腺癌的临床病理分析

目的 探讨中央坏死性乳腺癌的临床病理和免疫表型特征及其与基底细胞样型乳腺癌的关系.方法 观察35例中央坏死性乳腺癌的临床病理特点,并采用ER、PR、HER2、CK8/18、高相对分子质量CK(34βE12)、CK5/6、CK14、CK17、平滑肌肌动蛋白(SMA)、P63、波形蛋白、表皮生长因子受体(EGFR)进行EnVision法免疫组织化学染色.结果 35例患者的发病年龄为30～82岁,平均54.2岁.大体观察,肿物表现为边界较清楚的单中心结节,直径1.0～5.0 cm,平均2.4 cm.镜下,肿瘤中央有大片坏死或无细胞区,残留癌组织呈缎带状环绕在坏死区周围.中央坏死区表现为三种形态:24例主要由肿瘤性凝固性坏死组成,伴不同程度的纤维化或玻璃样变;8例以纤维化或瘢痕组织为主,见少量坏死癌组织残影;3例为梗死.周围残留癌组织32例为浸润性导管癌3级,3例为2级.20例伴有导管原位癌,5例伴有浸润性微乳头状癌,17例肿瘤周边见淋巴细胞浸润.31例中央坏死性乳腺癌中,基底细胞样标记(83.9%,26例)的阳性率明显高于肌上皮标记(38.7%,12例).基底细胞样型所占比例(20例,64.5%)显著高于管腔A型(3例,9.7%)、管腔B型(3例,9.7%)、HER2过表达型(4例,12.9%)和不表达型(1例,3.2%).20例基底细胞样型癌中,基底细胞样标记中CK5/6阳性18例,其余依次为CK17(8/10)、CK14(14/19)、EGFR(8/16).10例获得随访资料,随访15～42个月,平均21.5个月.9例疾病进展(因乳腺癌复发、转移或死亡),中位无病生存和总生存时间分别为14.0和18.0个月.平均和中位疾病进展时间分别为16.6和13.0个月.结论 中央坏死性乳腺癌具有独特的、容易识别的形态特点,大多显示基底细胞样免疫表型,预后差,是基底细胞样型乳腺癌的典型代表.     

乳腺癌细胞核形态定量分析与临床病理特征的关系

目的：观察乳腺癌细胞核形态参数,探讨其与ER、PR、HER-2表达和临床病理特征的关系。方法收集388例乳腺癌标本,根据ER、PR和HER-2三种抗体的免疫组化标记结果,将乳腺癌分为管腔A( Luminal A)型、管腔B( Luminal B)型、HER-2过表达型和基底细胞样( Basal-like)型,各组行HE染色后通过图像分析软件测量细胞核参数,应用统计学分析各组间的差异,并通过电话或住院病例随访。结果各组乳腺癌细胞核等圆直径、面积及边缘周长差异有统计学意义( P均<0.05);ER+/PR+病例细胞核形态定量与ER-/PR-病例比较,差异有统计学意义( P<0.05);ER-/PR-病例组织学分级多为Ⅲ级,生存率低于ER+/PR+病例(P<0.05)。 Luminal A型乳腺癌的无病生存期高于Basal-like型(P<0.05),总生存期高于HER-2过表达型(P<0.05)和Basal-like型(P<0.05)。结论乳腺癌细胞核形态定量差异有显著性,对其分子分型有一定的参考价值。 ER、PR和HER-2免疫组化标记结合细胞核形态学测量结果对乳腺癌的治疗和预后的评估有重要意义。     

雄激素受体在乳腺癌中的表达及其与雌、孕激素受体和HER2的关系

目的 研究雄激素受体(AR)在乳腺浸润性导管癌中的表达及其与雌激素受体(ER)、孕激素受体(PR)和HER2状态的关系,探讨其作为乳腺癌治疗靶点的可行性.方法 采用免疫组织化学EnVision法检测AR、ER、PR、HER2在175例乳腺浸润性导管癌中的表达,依据结果分为腺腔A型、腺腔B型、HER2过表达型和三阴性型(ER-/PR-/HER2-)组.结果 175例中AR阳性88例(50.3%),AR表达与ER、PR、HER2均呈正相关(P＜0.01).腺腔A型53例(30.3%),腺腔B型33例(18.9%),HER2过表达型23例(13.1%),三阴性型66例(37.7%),AR阳性率分别为56.6%(30/53),75.8%(25/33)、47.8%(11/23)和33.3%(22/66),组间AR阳性率差异显著(x2=17.054,P=0.001).三阴性型组AR阳性者核分裂象较少(x2=5.140,P=0.023),腺腔A型组AR阳性者多为年轻患者(x2=4.567,P=0.033),差异有统计学意义.其他组内AR表达与否和临床病理学特征比较无统计学意义.结论 AR在乳腺癌中有较高的阳性率,可作为乳腺癌,特别是三阴性型乳腺癌的治疗靶点.     

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.     

Identification of different subtypes of breast cancer using tissue microarray

Breast cancer may be classified into luminal A, luminal B, HER2+/ER-, basal-like and normal-like subtypes based on gene expression profiling or immunohistochemical (IHC) characteristics. The main aim of the present study was to classify breast cancer into molecular subtypes based on immunohistochemistry findings and correlate the subtypes with clinicopathological factors. Two hundred and seventeen primary breast carcinomas tumor tissues were immunostained for ER, PR, HER2, CK5/6, EGFR, CK8/18, p53 and Ki67 using tissue microarray technique. All subtypes were significantly associated with Malay ethnic background (p=0.035) compared to other racial origins. The most common subtypes of breast cancers were luminal A and was significantly associated with low histological grade (p<0.000) and p53 negativity (p=0.003) compared to HER2+/ER-, basal-like and normal-like subtypes with high histological grade (p<0.000) and p53 positivity (p=0.003). Luminal B subtype had the smallest mean tumor size (p=0.009) and also the highest mean number of lymph nodes positive (p=0.032) compared to other subtypes. All markers except EGFR and Ki67 were significantly associated with the subtypes. The most common histological type was infiltrating ductal carcinoma, NOS. Majority of basal-like subtype showed comedo-type necrosis (68.8%) and infiltrative margin (81.3%). Our studies suggest that IHC can be used to identify the different subtypes of breast cancer and all subtypes were significantly associated with race, mean tumor size, mean number of lymph node positive, histological grade and all immunohistochemical markers except EGFR and Ki67.     

Identification of a basal-like subtype of breast ductal carcinoma in situ

Microarray profiling of invasive breast carcinomas has identified subtypes including luminal A, luminal B, HER2-overexpressing, and basal-like. The poor-prognosis, basal-like tumors have been immunohistochemically characterized as estrogen receptor (ER)-negative, HER2/neu-negative, and cytokeratin 5/6-positive and/or epidermal growth factor receptor (EGFR)-positive. The aim of this study was to determine the prevalence of basal-like ductal carcinoma in situ in a population-based series of cases using immunohistochemical surrogates. A total of 245 pure ductal carcinoma in situ cases from a population-based, case-control study were evaluated for histologic characteristics and immunostained for ER, HER2/neu, EGFR, cytokeratin 5/6, p53, and Ki-67. The subtypes were defined as: luminal A (ER+, HER2-), luminal B (ER+, HER2+), HER2 positive (ER-, HER2+), and basal-like (ER-, HER2-, EGFR+, and/or cytokeratin 5/6+). The prevalence of breast cancer subtypes was basal-like (n = 19 [8%]); luminal A, n = 149 (61%); luminal B, n = 23 (9%); and HER2+/ER-, n = 38 (16%). Sixteen tumors (6%) were unclassified (negative for all 4 defining markers). The basal-like subtype was associated with unfavorable prognostic variables including high-grade nuclei (P < .0001), p53 overexpression (P < .0001), and elevated Ki-67 index (P < .0001). These studies demonstrate the presence of a basal-like in situ carcinoma, a potential precursor lesion to invasive basal-like carcinoma.     

Intratumoral expression level of epidermal growth factor receptor and cytokeratin 5/6 is significantly associated with nodal and distant metastases in patients with basal-like triple-negative breast carcinoma

Triple-negative (TN) breast carcinoma, characterized by estrogen receptor, progesterone receptor, and HER2 negativity, is a group of aggressive tumors that can be further classified into 2 subtypes: basal-like, defined as CK5/6 and/or epidermal growth factor receptor (EGFR) positive by immunohistochemistry; and non-basal-like. Clinical characteristics and tumor profiles were analyzed in 105 cases of TN tumors. Among these cases, 35 had distant metastasis, 34 had axillary nodal metastasis only, and 36 were nodal negative. Our results indicate basal-like TN breast tumors with nodal and distant metastases are significantly associated with a higher intratumoral expression of EGFR and CK5/6 compared to those in the nodal negative group. High level of intratumoral EGFR and CK5/6 expression may play a role in development of nodal or distant metastases in patients with basal-like TN tumors and may be predictive of metastatic disease. Furthermore, EGFR targeted therapy may be potentially useful in the treatment of basal-like TN breast cancer.     

Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma.

Microarray profiling of invasive breast carcinomas has identified five distinct subtypes of tumors (luminal A, luminal B, normal breast-like, HER2 overexpressing, and basal-like) that are associated with different clinical outcomes. The basal-like subtype is associated with poor clinical outcomes and is the subtype observed in BRCA1-related breast cancers. The aim of this study was to characterize the histologic and immunophenotypic properties of breast basal-like carcinomas that were first positively identified using DNA microarray analysis. Detailed histologic review was performed on 56 tumors with known microarray profiles (23 basal-like, 23 luminal, and 12 HER2+). Immunohistochemistry for estrogen receptor (ER), HER2, EGFR, smooth muscle actin (SMA), p63, CD10, cytokeratin 5/6, cytokeratin 8/18, and vimentin was performed on 18 basal-like, 16 luminal, and 12 HER2+ tumors. The basal-like tumors were grade 3 ductal/NOS (21/23) or metaplastic (2/23) carcinomas that frequently showed geographic necrosis (17/23), a pushing border of invasion (14/23), and a stromal lymphocytic response (13/23). Most basal-like tumors showed immunoreactivity for vimentin (17/18), luminal cytokeratin 8/18 (15/18), EGFR (13/18), and cytokeratin 5/6 (11/18), while positivity for the myoepithelial markers SMA (4/18), p63 (4/18) and CD10 (2/18) was infrequent. All basal-like tumors tested were ER- and HER2-. Morphologic features significantly associated with the basal-like subtype included markedly elevated mitotic count (P<0.0001), geographic tumor necrosis (P=0.0003), pushing margin of invasion (P=0.0001), and stromal lymphocytic response (P=0.01). The most consistent immunophenotype seen in the basal-like tumors was negativity for ER and HER2, and positivity for vimentin, EGFR, cytokeratin 8/18, and cytokeratin 5/6. The infrequent expression of myoepithelial markers in basal-like carcinomas does not support a direct myoepithelial cell derivation of these tumors. These findings should further assist in the identification of basal-like carcinomas in clinical specimens, facilitating treatment and epidemiologic studies of this tumor subtype.     

Basal-HER2 phenotype shows poorer survival than basal-like phenotype in hormone receptor-negative invasive breast cancers

Previous studies have shown conflicting results on prognostic significance of basal-like breast tumors, but hormone receptor is a confusing factor in most of the prognostic evaluations. We aimed to characterize the prognostic features of basal-like tumors without the influence of hormone receptor status in a series of hormone receptor-negative breast tumors. Using tissue microarray and immunohistochemistry methods, according to the expression of HER2 and basal markers (CK5/6, CK14, EGFR), we categorized 713 consecutive hormone receptor-negative invasive breast cancers into 3 subtypes: HER2 (HER2+), basal-like (HER2-, any basal marker+), and null (HER2-, all basal markers-). The HER2 phenotype was subdivided into pure-HER2 (HER2+, all basal markers-) and basal-HER2 (HER2+, any basal marker+) subgroups. Expression of p53, p63, vimentin, and BRCA1 was assessed immunochemically. Basal-like tumors showed significantly higher grade, more frequent recurrence, and higher expression of vimentin and p63 than HER2 and null phenotypes. Basal-HER2 phenotype had significantly younger mean age and expressed a higher level of p53 and vimentin like basal-like and/or HER2 phenotypes. However, unlike all the other hormone receptor-negative phenotypes, they highly expressed BRCA1. No significant difference was found in 5-year survival among basal-like and the other hormone receptor-negative phenotypes, except for basal-HER2, which showed poorer 5-year overall survival than basal-like tumors. In conclusion, although basal-like breast tumors have distinct clinicopathologic and immunohistochemical features, they have similar 5-year survival compared with the other hormone receptor-negative tumors including HER2 and null phenotypes. However, there exists a small group of hormone receptor-negative tumors expressing HER2 and basal markers simultaneously. This small group of tumors showed significantly poorer 5-year overall survival than basal-like breast tumors and might require different treatment strategy.     

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.     

Molecular classification predicts survival for breast cancer patients in Vietnam: a single institutional retrospective analysis

Background: The Bhagarva surrogate molecular subtype definitions classify invasive breast cancer into seven the different subgroups based on immunohistochemical (IHC) criteria according to expression levels of markers as ER, PR, HER2, EGFR and/or basal cytokeratin (CK5/6) which are different in prognosis and responsiveness to adjuvant therapy. Purpose: The present study aimed to classify primary breast cancers and directly compares the prognostic significance of the intrinsic subtypes. Methods: The current study was conducted on 522 breast cancer patients who had surgery, but had not received neoadjuvant chemotherapy, from 2011 to 2014. The clinicopathologic characteristics were recorded. IHC staining was performed for ER, PR, HER2, Ki67, CK5/6, EGFR and D2-40 markers. All breast cancer patients were stratified according to Bhagarva criteria. The followed-up patients’ survival was analyzed by using Kaplan-Meier and Log-Rank models. Results: The luminal A (LUMA) was observed at the highest rate (32.5%). Non-basal-like triple negative phenotype (TNB-) and Luminal A HER2-Hybrid (LAHH) were the least common (3.3% in both). LUMA and luminal B (LUMB) were significantly associated with better prognostic features compared to HER2, basal-like triple negative phenotype (TNB+) and TNB-. Statistically significant differences were demonstrated between overall survival (OS), disease-free survival (DFS) and molecular subtypes (P<0.05), of which LUMB and LUMA had the highest rate of OS and DFS being 97.2 and 93.7%; and 97.2 and 90.5%, respectively. Conversely, HER2 revealed the worst prognosis with the lowest prevalence of OS and DFS (72.5 and 69.9%, respectively). Conclusion: The molecular subtypes had a distinct OS and DFS. The intrinsic stratification displayed inversely to clinicopathological features in breast cancer.     

P-cadherin and cytokeratin 5: useful adjunct markers to distinguish basal-like ductal carcinomas in situ

Gene expression profiles of invasive breast carcinomas have identified a subgroup of tumours with worse prognosis, which have been called "basal-like". These are characterized by a specific pattern of expression, being estrogen receptor (ER) and HER2 negative, and frequently expressing at least one basal marker such as basal cytokeratins or epidermal growth factor receptor (EGFR). Previously, our group characterized basal-like tumours in a series of invasive breast carcinomas using P-cadherin (P-CD), p63 and cytokeratin 5 (CK5). Based on that study, we hypothesized that those high-grade basal-like invasive carcinomas might have a pre-invasive counterpart, which could be identified using the same approach. A series of 79 ductal carcinomas in situ (DCIS) were classified into distinct subgroups according to their ER, HER2 and basal markers expression. Luminal DCIS expressed ER and constituted 64.6% of the series; the HER2 overexpressing tumours did not express ER and represented 25.3% of the cases, whereas 10.1% lack the expression of ER and HER2 and expressed at least one basal marker (P-CD, CK5, CK14, p63, vimentin and/or EGFR). These basal-like DCIS were mostly high-grade, with comedo-type necrosis, and consistently showed expression of P-CD and CK5. In conclusion, DCIS with a basal-like phenotype represent a small percentage in our series, being P-CD and CK5, the most useful adjunct markers to distinguish this subset of carcinomas in situ of the breast.