Keratin expression in the normal breast and in breast carcinoma

The immunohistochemical reactivities of 69 cases of breast carcinoma were examined on methacarn-fixed, paraffin-embedded sections using eight different monoclonal antibodies which recognize one or a few keratin polypeptides. In the normal breast, the monoclonal antibodies RPN1162, RPN1165 and AE1 stained almost all the luminal cells but not the basal (myoepithelial) cells. The monoclonal antibodies 35BH11, M20, CK5 and CK8.12 stained only a subset of the luminal cells. In contrast, 312C8-1 stained basal cells but not luminal cells. All the tumour specimens reacted with AE1, while over 80% of them also reacted with 35BH11 (57/69), CK5 (57/69) and RPN1165 (55/69); 30% reacted with CK8.12 (21/69) and 16% with RPN1162 (11/69). Basal cell-specific keratin, as defined by 312C8-1, was detected in only 1% of cases (1/69). Monoclonal antibodies to different keratin polypeptides may be of use in the characterization and subdivision of breast cancer.     

乳腺癌波形蛋白表达的生物学意义

应用波形蛋白童克隆抗体（Ｖｉｍ）免疫组化ＡＢＣ法对７５例乳腺癌进行标记分析。结果显示，Ｖｉｍ阳性３４例，阳性率４５．３％。统计分析表明，Ｖｉｍ表达与肿瘤的组织学分级有关（Ｐ＜０．００５），Ｖｉｍ阳性肿瘤的ＡｇＮＯＲ均数大于阴性组）Ｐ＜０．０１），Ｖｉｍ阳性组病人的５年生存率低（Ｐ＜０．００５）。以上提示了乳腺癌Ｖｉｍ表达是肿瘤分化低、细胞增生活跃和病人预后不良的指征。     

乳腺癌组织内微血管分布的定量研究

用ＦⅧ相关抗原免疫组化染色定量观察４８例乳腺浸润癌。结果表明：有腋窝淋巴结转移组血管密度为每ｍｍ２１３５．４±４７．８个，无腋窝淋巴结转移组血管密度为每ｍｍ２９６．１±３１．４个，两组间的差异有显著意义（Ｐ＜０．０１）。同时血管的分布在癌组织旁每ｍｍ２１４２．４±４９．５个，在癌肿中央为每ｍｍ２９３．５±２８．６个，两组差异亦具有显著意义。结果揭示乳腺癌组织内血管生成与肿瘤的生长及腋窝淋巴结的转移关系密切。     

乳腺分泌脂质性癌临床病理分析

目的 探讨乳腺分泌脂质性癌(breast lipid-secreting carcinoma)临床病理特征.方法 对3例进行病理组织学观察、特殊染色PAS、AB染色和免疫组化标记ER、PR、Ki-67、c-erbB-2、p53等.结果 3例均为女性,年龄分别为44、54、50岁,均可触及乳腺肿块,肿瘤境界欠清楚,镜下肿瘤边缘呈浸润性生长,肿瘤主要由空泡状细胞即组织细胞样细胞和其它少量皮脂腺样细胞、大汗腺样细胞组成.AB、PAS染色阴性.免疫组化(SP法)瘤细胞示:ER、PR阴性、c-erbB-2、Ki-67、p53不同程度阳性.3例均术中快速切片诊断癌后,行乳腺改良根治手术.结论 乳腺分泌脂质性癌是一种相对少见,恶性度较高,预后较差的肿瘤,诊断主要依靠病理组织检查及特殊染色.免疫标记可帮鉴别诊断及判断预后.     

乳腺基底细胞样癌的临床病理观察

目的 探讨乳腺基底细胞样癌(basal-like carcinoma,BLC))的临床病理特征、免疫表型特点及预后.方法 收集乳腺BLC 12例,总结其临床资料、大体及组织病理学特征,并进行免疫组化EnVision法染色.选用的抗体包括CK5/6、vimentin、CK8、ER、PR及c-erbB-2等.结果 本组患者均为女性,发病平均年龄40.4岁.12例乳腺BLC均为组织学Ⅲ级.肿瘤表现为无腺管的富于细胞的实性结构,周围有较少的纤维结缔组织间隔;大多数表现为推进式生长方式,周围有大量淋巴细胞浸润;排列呈实性巢状、片状、团块状及粗大带状结构伴有片状地图样坏死,肿瘤中央可出现无细胞结构的纤维瘢痕.肿瘤细胞胞质少呈合体状,核为圆形、卵圆形,胞核胞质比例高,核分裂象活跃.12例乳腺BLC的免疫表型均为ER、PR及c-erbB-2阴性,而CK5/6、CK8及vimentin阳性.结论 乳腺BLC是一种新的乳腺癌类型,具有独特的免疫组化特征、组织形态学特点及生物学特性,应作为一种独立的乳腺癌亚型加以认识.     

Cyclooxygenase-2 expression: a potential prognostic and predictive marker for high-grade ductal carcinoma in situ of the breast

AIMS: To study cyclooxygenase-2 (COX-2) expression in ductal carcinoma in situ (DCIS) of the breast and its association with histological features. COX-2, an inducible prostaglandin synthase, has been shown to be important in mammary carcinogenesis, being associated with increased tumour size and unfavourable outcome in breast cancer. Animal studies indicate that COX-2 inhibition is effective in the prevention and treatment of mammary cancers. METHODS AND RESULTS: Fifty-one cases of DCIS diagnosed during 1990-2000 were reviewed. Immunohistochemistry for COX-2 was performed and the COX-2 staining scores were correlated with histological features. The majority of cases [41 of 51 (80%)] had positive COX-2 staining, of which 13 cases (25%) had strong staining. High nuclear grade DCIS was significantly associated with increased COX-2 staining (P = 0.04). CONCLUSIONS: High-grade lesions are known to be associated with a higher recurrence rate following excision and are often oestrogen receptor negative, and as such, may be less responsive to adjuvant tamoxifen therapy. There is a need to examine further the role of COX-2 expression in DCIS, as both a prognostic and predictive factor.     

A rare case of secretory breast carcinoma in a male adult with axillary lymph node metastasis

Secretory breast carcinoma is a rare tumor originally described in children but occurring equally in adult population, especially in women. This unusual subtype has a generally favorable prognosis, although several cases have been described in adults with increased aggressiveness and a risk of metastases even death. So far, merely ten cases of secretory breast carcinoma with metastatic axillary lymph node in male were reported. Here, we describe the eleventh case, a 24-years-old male who presented with a painless mass in the right breast was diagnosed to be “secretary breast carcinoma”, and subsequently underwent modified radical mastectomy and adjuvant chemotherapy.     

Metaplastic breast carcinoma: a retrospective study of 26 cases

Metaplastic breast carcinoma is a rare invasive breast cancer. Metaplastic breast carcinoma is mainly characterized by an epithelial or mesenchymal cell population mixed with adenocarcinoma. We collected 26 cases of metaplastic breast carcinoma in the First Affiliated Hospital of Bengbu Medical College from 2008 to 2014. Tumor size, tumor grade, vascular invasion, ER/PR status, histologic classification, and HER2/neu status were assessed for all cases and the literature was reviewed. Clinicopathologic characteristics of patients diagnosed with metaplastic breast carcinomas and its key points of differential diagnosis were discussed. All patients were female, with the median age of 50 years. The mean tumor size was 3.2 cm. 4 subtypes of metaplastic breast carcinomas were documented. Fibromatosis-like metaplastic carcinomas are typically characterized by wavy, intertwined, gentle spindle cells. When the tumor components are almost squamous cell carcinoma components and the primary squamous cell carcinoma of other organs and tissues are excluded, we can diagnose breast squamous cell carcinoma. In spindle cell carcinoma, atypical spindle cells are arranged in many ways and are usually accompanied by inflammatory cell infiltrate. Cancer with interstitial differentiation has mixed malignant epithelial and mesenchymal differentiation, and the mesenchymal components are diverse. Most tumors are triple negative. At present, surgical resection combined with chemotherapy or radiation therapy is the most effective and acceptable method for treating metaplastic breast carcinoma.     

乳腺浸润性导管癌中促性腺激素释放激素受体的表达及意义

目的 探讨促性腺激素释放激素受体(gonadotropin-releasing hormone,GnRHR)在乳腺浸润性导管癌中的表达及意义.方法 采用免疫组化方法 检测50例乳腺浸润性导管癌及18例正常乳腺组织中的GnRHR.结果 乳腺浸润性导管癌中GnRHR的阳性表达为68%(34/50).其中乳腺癌 G1组的阳性表达(92.3%,12/13)与G3组的阳性表达(46.2%,6/13)之间的差异有统计学意义(P<0.05).乳腺癌G3组的阳性表达和正常乳腺组织的阳性表达(94.4%,17/18)之间的差异有统计学意义(P<0.01).结论 大多数正常乳腺组织的GnRHR虽有表达,但呈弱阳性表达,而多数浸润性导管癌GnRHR则呈强阳性表达,提示乳腺组织的分化程度影响肿瘤组织内GnRHR的表达.     

Pleomorphic carcinoma of the breast: clinicopathological analysis of 26 cases of an unusual high-grade phenotype of ductal carcinoma

AIMS: Pleomorphic carcinoma is a poorly described entity whose phenotype is not well recognized as within the morphological spectrum of breast carcinoma. The purpose of this report is to describe the clinicopathological features of this tumour, and to promote its recognition as an unusual high-grade morphological variant of mammary ductal carcinoma. METHODS AND RESULTS: Histological slides of breast carcinomas (N = 64) coded between 1978 and 1995 as having pleomorphic or anaplastic features were reviewed. Pleomorphic carcinoma (N = 26) was diagnosed when > or = 50% of the tumour manifested a pleomorphic cell population (> sixfold variation in nuclear size). Tumours of lobular origin were excluded. All neoplasms occurred in women with a mean age of 53 years. Patients underwent biopsy and/or mastectomy (n = 24) or lumpectomy (n = 2). The tumours' mean size was 54 mm. All were high-grade neoplasms. The pleomorphic cell population comprised 50-100% of the tumour; 31% had a prominent spindled morphology. Fifty-eight per cent of the tumours were initially misclassified by referring pathologists as sarcomas or carcinomas, possibly metastatic. Adjacent DCIS or a transition to classic ductal carcinoma was present in 73%. Five (19%) patients were stage I and three (12%) had stage IV disease. Axillary dissections yielded > or = 3 (mean 7.2) positive lymph nodes in 52%. Most (68%) tumours were aneuploid; a high S-phase (> 10%) was present in 63%. All neoplasms were ER negative and all but one were PR negative. p53 expression was present in 71%; none expressed bcl-2. c-erbB-2 was detected in four (19%) node-positive and in 0 (0%) node-negative cases (P = 0.01). Of 16 patients with follow-up, 6 (38%) were disease-free (mean, 74 months), four (25%) alive with disease (mean, 33 months) and six (38%) dead of disease at a mean of 22 months. CONCLUSIONS: Pleomorphic carcinoma is a prognostically unfavourable lesion and represents the extreme end of the morphological spectrum of grade III infiltrating ductal carcinoma.     

Expression of somatostatin type 2A receptor correlates with estrogen receptor in human breast carcinoma

Somatostatin type 2A receptor (sstr2A) has been shown to be directly involved in the transduction of antiproliferative effects and also to be the most predominant sstr subtype in human normal breast epithelium, as well as in human breast carcinoma. We investigated the immunoreactivity of sstr2A in 34 cases of human breast carcinoma and correlated these findings with the immunoreactivity of the estrogen receptor (ER), epidermal growth factor receptor (EGFR), transforming growth factor α(TGFα) and insulin like growth factor I (IGF-I). We detected sstr2A immunoreactivity in normal mammary tissue, and in 27 of 34 (79%) breast carcinomas. The sstr2A immunoreactivity was localized on the cellular membrane, however, weak cytoplasmic immunoreactivity was also observed. Sstr2A immunoreactivity was heterogenously distributed in the whole tumor section. There was a statistically significant correlation between sstr2A and ER immunoreactivity in the same tumor. No statistically significant correlation was found between sstr2A immunoreactivity and immunoreactivity for EGFR, TGFα and IGF-I or the patients' age.     

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.     

Specific morphological features predictive for the basal phenotype in grade 3 invasive ductal carcinoma of breast

AIMS: Cytokeratin (CK) 14, a myoepithelial marker, is also expressed in a proportion of breast carcinomas. There is evidence that these tumours show a differing metastatic pattern and clinical outcome from other invasive ductal carcinomas (IDCs) and may need different management. Currently, they are not identified in routine practice and no morphological guidelines exist to aid their identification. The aim of this study was to analyse the histological features of CK14+ IDC. METHODS AND RESULTS: A detailed histological review of 453 grade 3 IDCs revealed 88 (19.4%) that expressed CK14. Assessment was made independently by two pathologists using a standardized 'tick-box' proforma covering grade, architectural and cytological features. The results were analysed using logistic regression to identify features that predicted for basal phenotype. Concordance between the two pathologists was fair to good for most parameters (kappa 0.4-0.6). On multiple logistic regression, the basal phenotype was highly significantly associated with the presence of a central scar (P = 0.005), tumour necrosis (P < 0.0001), presence of spindle cells (P = 0.006) or squamous metaplasia (P < 0.0001), high total mitotic count (> 40 per 10 high-power field) (P = 0.0002) and high nuclear-cytoplasmic ratio (P = 0.0002). CONCLUSIONS: Specific morphological features are strongly associated with basal-like breast carcinoma. These could be used in routine diagnostic practice to identify this important subset of tumours.     

乳腺肌上皮癌3例临床病理特征分析

目的探讨乳腺肌上皮癌的临床表现、组织形态学改变和免疫表型特征。方法采用HE及免疫组化Leica BOND-MAX全自动染色仪Bond Polymer Refine Detection法,对3例乳腺肌上皮癌进行染色,并复习相关文献。结果乳腺肌上皮癌的癌组织多由梭形细胞组成,部分病例可见上皮样细胞、浆样细胞和透明细胞,呈实性片状、肺泡样、条索状排列;核分裂象易见;无坏死;可发生腋窝淋巴结转移。免疫表型:3例均表达CK、EMA、CD10、p40、actin、Calponin、p63;2例表达CK5/6、CK14、SMA;1例表达S-100蛋白、D2-40、CAM5.2;CD117、CD34、ER、PR、C-erb B-2/HER-2和desmin均不表达;Ki-67增殖指数为10%~20%。结论肌上皮癌细胞形态多样,结合免疫组化组合标记可做出明确诊断,治疗方式以乳腺癌根治术为主。     

Invasive micropapillary carcinoma of the breast: clinicopathological and immunohistochemical study

Invasive micropapillary carcinoma (IMPCa) of the breast refers to a unique variant of invasive ductal carcinoma, but its biological behavior has not been elucidated well. We analyzed 16 IMPCa cases (10 pure type, six mixed type). The incidence of IMPCa was 1.0% of all primary breast carcinoma. High nuclear grade (75.0%), as well as poorly differentiated histological grade (81.3%), was frequently seen. Lymph node metastases were evident in 92.9% of the examined cases, and about half of them showed more than 10 positive nodes. Comparison between serially experienced invasive ductal carcinoma, not otherwise specified (IDC-NOS), revealed that both high nuclear grade and poor histological grade were significantly more frequent ( P  < 0001), there was a lower frequency of positive estrogen receptor/progesterone receptor ( P  < 0.05, P  < 0.01), a higher frequency of HER-2 overexpression ( P  < 0.025), and more frequent lymph node metastases ( P  < 0.05) in IMPCa. The comparison between lymph node positive IDC-NOS did not show any statistically significant differences in frequency for positive p53, matrix metalloproteinase protein-2 (MMP-2), vascular endothelial growth factor (VEGF) or E-cadherin. However, IMPCa showed a significantly increased number of blood vessels counted by CD34 immunostains ( P  < 0.05). These results suggest that IMPCa is, at least, the same or more aggressive than lymph node positive cases of IDC-NOS. Hence, not only the high incidence of lymph node metastases but also distant, blood-borne metastases may be important.     

乳腺大汗腺癌的形态学与免疫表型特征

目的 观察乳腺大汗腺癌(apocrine carcinoma，AC)的形态学和免疫表型特征，并探讨其诊断标准。方法 对HE染色片中显示有大汗腺细胞学特点的30例乳腺癌标本进行组织学观察和免疫组化S—P法检测，并选取5例大汗腺化生(apocrine metaplasia，AM)及2例大汗腺腺病(apocrine adenosis，AA)和AA伴导管原位癌(DCIS)1例标本作对照组。使用的-抗包括GCDFP—15、Mucin—1、AR、ER、C—erbB-2、Ki-67。结果 ①8例被确定为AC，均为高核级，其中大汗腺导管原位癌(ADCIS)1例、ADCIS伴浸润性大汗腺癌(IAC)5例，IAC伴导管原位癌(DCIS)2例。镜下AC细胞的共同特征为：细胞大，胞界清，胞质丰富，深嗜伊红染，颗粒状；核大、圆，核仁常大而突出。依据胞质形态可分为：A型，胞质深伊红染，有数量不等的清晰颗粒；B型，胞质内大量细空虚的小泡，可聚呈泡沫状，类似组织细胞或皮脂腺细胞；C型，胞质浅染、均质，如细磨砂玻璃样；②8例AC与5例AM及2例AA均共同表达GCDFP—15、AR、Mucin—1及Ki-67；除1例外，ER均不表达；③AC的GCDFP—15的表达与大汗腺化生不同：前者呈胞质内弥漫颗粒或空泡状，表达有异质性；后者阳性颗粒聚成小球状团簇，位于细胞质的核上区。④AR平均阳性细胞数在Ac及AM分别为33．4％及93．8%；Ki-67平均阳性细胞数在AC及AM分别为52．4％及40％。结论 AC的诊断须具备3项标准：①HE细胞形态成分90％以上符合Ac型细胞；②GCDFP—15阳性，阳性细胞数占癌细胞总数50％以上；⑧AR阳性，阳性细胞数大于癌细胞总数20％。     

组织细胞样乳腺癌临床病理学特征研究及文献复习

目的：观察组织细胞样乳腺癌的临床病理、免疫组织化学特点及鉴别诊断,并复习相关文献。方法：收集北大人民医院病理科2007~2014年及航空总医院病理科,建科以来的组织细胞样乳腺癌3例,分析其临床病理学及免疫组织化学特征,并采用FISH检测HER2基因的扩增水平。结果：镜下肿瘤细胞呈小巢或条索状生长。肿瘤细胞呈多边形,圆形,胞浆丰富,嗜酸,呈颗粒状、泡沫状,组织细胞样,细胞核呈圆形及卵圆形,染色质细腻,核仁不清楚,核轻度异型性,核分裂像不明显。免疫组织化学结果显示：所有3例样本CK(+)、CK7(+)、S100(–)、E-cadherin(–)、GCDFP 15(+)、CD68(–)。其中1例进行了HER2 FISH检测,结果为阴性。结论：组织细胞样乳腺癌是一种少见的特殊类型乳腺癌,在日常的诊断工作中,需结合免疫组织化学检查,以便排除其它肿瘤的可能性和明确诊断。     

Oestrogen receptor negativity as a marker for high-grade ductal carcinoma in situ of the breast

AIMS: To compare the morphological and immunohistochemical characteristics of oestrogen receptor (ER)-negative and ER-positive ductal carcinoma in situ (DCIS) of the breast, in an attempt to establish more objective criteria for the classification of DCIS. METHODS AND RESULTS: Sections of 64 cases of in-situ carcinoma of the breast were stained for ER, progesterone receptors (PgR), androgen receptors (AR), c-erbB-2 and p53, using the immunoperoxidase technique. The cases included 60 DCIS and four lobular carcinoma in situ (LCIS). Four DCIS lesions were associated with foci of microinvasion. The 60 DCIS cases included 31 high grade, 23 intermediate grade and six low grade. Twenty-four DCIS cases (40%) were ER-negative and 36 were positive. ER negativity was significantly associated with high nuclear grade (88% versus 27% for ER-positive cases, P < 0.001), PgR negativity (100% versus 25%, P < 0.001), c-erbB-2 positivity (79% versus 14%, P < 0.001) and p53 positivity (58% versus 6%, P < 0.001). There was no difference between ER-negative and -positive DCIS as regards AR expression, with 91% of cases in each group being AR-positive. Of the four cases of DCIS with microinvasion, three were ER- and PgR-negative, all four were c-erbB-2-positive and AR-positive and one was p53-positive. None of the four LCIS was ER, PgR or AR-negative and none was c-erbB-2- or p53-positive. CONCLUSIONS: There is a highly significant direct relationship between ER negativity in DCIS and high nuclear grade, PgR negativity and c-erbB-2 and p53 positivity. We suggest that immunohistological assessment of ER status may help in providing a more objective way of classifying DCIS.