Expression of EGFR and c-kit is associated with the basal-like phenotype in breast carcinomas of African women

Epidermal growth factor receptor (EGFR) and c-kit are tyrosine kinase growth factor receptors which are frequently expressed in basal-like breast carcinomas, and tyrosine kinase inhibition is now a promising strategy in treatment of breast cancer. The aim of this study was to evaluate the expression of EGFR and c-kit in breast cancer with special focus on the basal-like phenotype (BLP) and other prognostic factors in an African population. We analyzed 65 archival tissues immunohistologically. EGFR and/or c-kit were expressed in 55% of basal-like tumors. Expression of EGFR and/or c-kit was strongly associated with high histologic grade (P=0.001), high nuclear grade (P=0.017), high mitotic counts (P=0.002), ER negativity (P=0.003), PR negativity (P=0.007), and HER2 negativity (P=0.014). EGFR and/or c-kit positive tumors were more likely to express the BLP (OR 9.1, CI 2.6-32.0, P<0.0005) than the negative tumors. In conclusion, there is a high expression of EGFR and/or c-kit in basal-like breast carcinoma in this series from Uganda and their expression is associated with features of poor prognosis. More studies are required to assess the clinical significance of EGFR and c-kit in breast cancer patients in Uganda.     

The basal-like breast carcinoma phenotype is regulated by SLUG gene expression

Basal-like breast carcinoma is an aggressive form of breast cancer, characterized by the absence of oestrogen receptor and HER2 expression, the presence of cytokeratin 5 and epidermal growth factor receptor expression, and by the up-regulation of stem cell regulatory genes. We show here that tumour tissues expressing high levels of SLUG mRNA show a basal-like breast carcinoma phenotype and that such tumours also express high levels of stem cell-regulatory genes, ie CD133, Bmi1. Further, we show that stem/progenitor cells, isolated from ductal breast carcinoma and from normal mammary gland as mammospheres, express SLUG, CD133, and Bmi1 mRNA and show a phenotype similar to that of basal-like breast carcinoma. We also report that SLUG expression in tumour tissues correlates with that of the hypoxia survival gene carbonic anhydrase IX. In this regard, we report that the exposure of SLUG-negative/luminal-like MCF-7 cells to a hypoxic environment promotes the onset of the basal-like breast carcinoma phenotype, together with up-regulation of the SLUG gene, which in turn blunts oestrogen receptor-alpha and boosts carbonic anhydrase IX gene expression. Finally, we show that SLUG expression promotes the invasiveness of MCF-7 cells exposed to hypoxia and sustains the in vivo aggressiveness of hypoxia-selected, MCF-7-derived cells in xenografts. These data indicate that SLUG gene expression is part of a hypoxia-induced genetic programme which sets up a basal/stem cell-like, aggressive phenotype in breast cancer cells.     

Increased tumor cell expression of Axl is a marker of aggressive features in breast cancer among African women

Axl, a receptor tyrosine kinase belonging to the Tyro/Axl/Mer (TAM) family, has been shown to be overexpressed in breast cancer with poor outcome. Moreover, Axl was associated with a basal‐like phenotype (BLP) in these tumors. Our aim was to investigate Axl expression in breast cancers from an African population since these tumors are known to be aggressive and have a high frequency of the basal‐like phenotype. We studied 170 paraffin‐embedded breast carcinoma cases by tissue microarrays and immunohistochemical methods. In total, 128 tumor cases (75%) had strong Axl expression and 42 cases (25%) had weak or negative staining. Strong expression of Axl was associated with high tumor grade (p < 0.0005), estrogen receptor (ER) negativity (p = 0.024), p53 expression (p = 0.004), P‐cadherin positivity (p = 0.017), and basal‐like phenotypic profiles BLP2 (p = 0.033) and BLP3 (p = 0.022). In addition, Axl overexpression also showed an association with markers of tumor cell proliferation and tumor angiogenesis. In conclusion, our findings indicate strong expression of Axl in a high proportion of breast cancer cases among African women and associations with markers of aggressive features, indicating poor prognosis. These findings suggest Axl as a potential therapeutic target in this population.     

Expression of midkine and endoglin in breast carcinomas with different immunohistochemical profiles

The aim of this study was to investigate the midkine and endoglin expression in breast carcinomas with five different immunohistochemical profiles and their relevance to histopathologic and clinicopathologic features. We analyzed 161 archival tissues immunohistologically. The level of midkine expression in breast cancer significantly correlated with lymph node metastasis (p = 0.001) and TNM staging (p = 0.003). High microvessel density (MVD) was associated with higher midkine reactivity group (p = 0.036). Although the basal-like subtype had higher midkine expression level and MVD, no significant difference with the other breast cancer subtypes was found. In conclusion, midkine was a promising target for tumor prognosis in clinical diagnosis and treatment. This study found no significant differences in tumor angiogenesis in different molecular subtypes of breast cancer.     

Epidermal growth factor receptor gene amplification and protein overexpression in basal-like carcinoma of the breast

Shao M‐M, Zhang F, Meng G, Wang X‐X, Xu H, Yu X‐W, Chen L‐Y & Tse G M
(2011) Histopathology 59 , 264–273 Epidermal growth factor receptor gene amplification and protein overexpression in basal‐like carcinoma of the breast Aims: Epidermal growth factor receptor (EGFR) is frequently expressed in basal‐like breast cancer (BLBC). The aim of this study was to evaluate their correlation as detected by immunohistochemistry (IHC) or fluorescence in‐situ hybridization (FISH). Methods and results: IHC for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER) 2, cytokeratin (CK) 5/6 and EGFR, and FISH for EGFR amplification, were performed in 59 cases of BLBC. EGFR IHC results were scored semiquantitatively, and compared with its gene amplification status. ER, PR and HER2 were negative in all cases, whereas 35 and 55 cases were positive for CK5/6 and EGFR. For EGFR IHC, 20, 11, 11 and 17 cases showed a negative, a low, an intermediate or a high staining level, respectively, and seven cases showed gene amplification by FISH, with two, 19, 11 and 20 cases showing balanced monosony, disomy, trisomy, and polysomy respectively. Immunohistochemical expression in gene‐amplified tumours was significantly higher than in those without amplification, including balanced polysomy tumours. EGFR immunohistochemical expression also correlated with the EGFR/chromosome 7 ratio. High sensitivity (86%) and negative predictive value (98%) were achieved with high‐level immunohistochemical expression as a cut‐off to predict gene amplification. Conclusions: High‐level EGFR immunohistochemical expression correlated with and predicted EGFR amplification, and may be used as a screening method to exclude gene amplification.     

Independent prognostic value of the basal-like phenotype of breast cancer and associations with EGFR and candidate stem cell marker BMI-1

Aims:  To study the relationship between basal-like breast cancers, epidermal growth factor receptor (EGFR) and candidate stem cell markers (BMI-1, EZH2, Oct-4) in a population-based setting.
Methods and results:  Immunohistochemistry was evaluated in a series of 190 breast cancers. Basal-like phenotype (BLP) 1–5 was found in 4.3–14.3% of cases. EGFR was expressed in 9% of cases and associated with cytokeratin (CK) 5 and P-cadherin positivity, but not with survival; 28% of CK5+ cases were EGFR+. On multivariate analysis, basal-like differentiation and lymph node status were independent prognostic factors of comparable strength. BMI-1 positivity (42.6%) was associated with absence of basal-like features, oestrogen receptor positivity and low Ki67, but not related to survival. BMI was not associated with EZH2 expression, and these markers tended to show opposite associations with other variables, suggesting different roles in breast cancer. Oct-4 expression was not detected in this series.
Conclusions:  Basal-like features and lymph node status were strong and independent prognostic factors in this population-based series of breast cancer. Neither EGFR nor BMI-1 had significant prognostic impact, whereas EZH2 expression was associated with decreased survival. BMI-1 was inversely related to basal-like factors, and a stem cell phenotype of the basal-like subgroup could not be verified by this marker.     

Primary squamous cell carcinoma of the breast with unusual basal-HER2 phenotype

Objectives: To report three cases of primary squamous cell carcinoma of the breast with an unusual “basal-HER2” phenotype. Methods: Clinical data were analyzed. Morphological features were observed. Immunohistochemical study for ER, PR, HER2, Ki-67, CK 5/6, CK10/13, CK14, EGFR, P63 and FISH detection of HER2 gene amplification were performed. Results: Three patients were all female with 26, 57 and 66 years old. The tumors were 3 cm, 4 cm and 5 cm in size respectively. Morphologically, all three tumors were pure squamous cell carcinoma and entirely composed metaplastic squamous cells. Two tumors were moderately differentiated and one was poorly differentiated. All three patients were positive for P63 or CK10/13. All three tumors exhibited basal-HER2 phenotype: negative for ER and PR, positive for HER2 protein and HER2 gene amplification, and positive for at least two basal markers. Conclusions: SCC with basal-HER2 phenotype is an extremely rare subset of breast carcinoma. Since it may have worse prognosis than typical basal-like SCC, recognization of this unusual SCC in routine work may have obvious clinical significance.     

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.     

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.     

Centrally necrotizing carcinoma of the breast: clinicopathological analysis of 33 cases indicating its basal‐like phenotype and poor prognosis

Yu L, Yang W, Cai X, Shi D, Fan Y & Lu H
(2010) Histopathology 57 , 193–201 Centrally necrotizing carcinoma of the breast: clinicopathological analysis of 33 cases indicating its basal‐like phenotype and poor prognosis Aims: To investigate the clinicopathological features and immunophenotype of centrally necrotizing carcinoma (CNC) of the breast to ascertain its relationship to basal‐like phenotype and its prognosis. Methods and results: The clinical and pathological characteristics of 33 CNCs were reviewed. Immunohis‐tochemical study of oestrogen receptor, progesterone receptor, HER2, cytokeratin (CK) 8/18, high‐molecular‐weight CK (34βE12), CK5/6, CK14, CK17, smooth muscle antigen, p63, vimentin and epidermal growth factor receptor was performed. The striking feature of CNC was a central, necrotic or acellular zone surrounded by a ring‐like area of viable tumour cells. The central zone showed three morphological types: predominance of coagulative necrosis (21 cases), predominance of fibrosis and scar tissue (nine cases) and infarction (three cases). Tumour cells displayed invasive ductal carcinoma of high grade. The expression rate of basal‐like markers was higher than that of myoepithelial markers (87.9% versus 46.2%). Basal‐like subtype was shown by 63.6% of cases. The expression rate of CK5/6 (90.5%) was highest among basal‐like markers. Follow‐up data of 19 patients were available. Median progression‐free survival was 15.5 months. In 12 patients (63.2%), local recurrence and/or distant metastasis developed (median time to recurrence and/or metastasis, 14.0 months). Conclusions: CNC has distinctive morphological features, which mostly exhibit a basal‐like immunophenotype and poor prognosis. CNC is a typical representative of basal‐like breast cancer.     

Extensive extranodal metastases of basal-like breast cancer with predominant myoepithelial spindle cell differentiation

A differentiation towards myoepithelial cells has been demonstrated in several types of lesions in the breast. These include multifocal myoepitheliomatosis, the rare mixed tumor or pleomorphic adenoma, adenoid cystic carcinoma, adenomyoepithelioma and myoepithelial carcinoma (malignant myoepithelioma). Myoepithelial carcinoma is the only lesion purely composed of myoepithelial cells. All these tumors are benign and/or of low-grade malignancy, with the exception of malignant myoepithelioma. In contrast to the statement of the current World Health Organization (WHO), recent studies have reported that regional and distant metastases may occur in about 50% of pure myoepithelial carcinomas. The presented case of a breast carcinoma with dominant myoepithelial/spindle cell differentiation in a 58-year-old woman is an excellent example to document the highly aggressive biological behavior of this tumor phenotype. Despite an extensive chemotherapy and radiotherapy, the tumor was rapidly progressive, forming a finally exulcerating local tumor relapse and widespread metastases to the myocardium, lungs, liver, kidneys and skin. Similarities in morphology and biological behavior compared to patients with “triple-negative” (hormone receptor and Her2) monophasic sarcomatoid carcinomas and pure spindle cell sarcomas are discussed.     

Mucinous cystadenocarcinoma of the breast with a basal-like immunophenotype

Mucinous cystadenocarcinoma (MCA) of the breast is extremely rare and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. A case of MCA is reported in a 41-year-old woman. Mammographic and ultrasonographic examinations showed an irregularly shaped 10.0 × 8.0 × 5.5 cm lesion with patching calcification in the upper outer quadrant of the left breast. The gross examination revealed that the tumor has a well-circumscribed edge with a gelatinous cut surface and hemorrhage and necrosis were also noticed in the mass. Microscopically, the mass resembled mucinous cystic neoplasm of the ovary and pancreas closely, with cystic areas lined by columnar mucinous cells and associated with abundant extracellular and intracellular mucin, which is distinctively different from mucinous carcinoma with typically nests of low grade neoplastic cells floating in the mucin pool. The tumor cells were positive for CK7, CK20 and CDX2 were negative and displayed a typical immunophenotype of basal-like breast cancer (ER, PR, HER2 were negative, CK5/6 and EGFR were positive). Metastatic carcinoma was identified in three of 14 axillary lymph nodes. We describe here a very unusual case of breast MCA with basal-like immunophenotype.     

Osteoclast-like giant cells in invasive breast cancer predominantly possess M2-macrophage phenotype

Breast carcinoma with osteoclast-like giant cells (OGCs) is a rare tumor; however, their clinicopathological aspects remain unclear. We described the clinicopathological characteristics of 8 patients with breast carcinoma with OGCs. Immuno-phenotypes of the OGCs were comparatively examined with that of foreign body giant cells (FBGCs) in 4 cases of granulomatous reaction (GR) without cancerous elements. In most cancers, tumors displayed cribriform and tubular growth patterns. Three cases showed moderate to high nuclear grade, while all the other tumors had low nuclear grade. Six patients were estrogen receptor (ER) positive, while triple negative phenotype was identified in 2 patients. During the follow-up period, 1 patient had local recurrence of the tumor, and all the patients remained alive. All OGCs and FBGCs expressed CD68, a pan-macrophage marker. OGCs in all the breast cancers showed moderate to high expression of CD163 — a marker of M2-macrophage with pro-tumoral function — whereas its expression in FBGCs was low to moderate (p = 0.04). CD86 — a marker of M1-macrophage with a tumoricidal activity — was positive in the OGCs of 3 breast cancers, and in the FBGCs of 3 GR cases (p = 0.15). The expression of CD163 was significantly higher than that of CD86 in the OGCs of breast cancer (p < 0.001), whereas they were comparable in the FBGCs of GR (p = 0.79). In summary, we found that breast carcinoma with OGCs mostly exhibited cribriform and tubular growth pattern, ER positivity, and predominantly possessed the M2-macrophage phenotype. However, the clinical significance of OGCs in breast cancer needs to be elucidated in further studies involving a larger number of cases.     

GABRP基因在基底样三阴乳腺癌中的差异表达

目的:探索GABRP基因在基底样三阴乳腺癌(basal-like Triple negative breast cancer,BLTNBC)中的表达,为临床提供预后诊断分子标志物.方法:通过生物信息学分析比较GABRP基因的表达;采用定量PCR方法检测GABRP基因在乳腺癌细胞系及104例乳腺癌石蜡样本中的差异表达,并采用相关性分析、卡方检验及Fisher精确概率法分析GABRP基因与细胞增殖、淋巴结转移、ER及HER-2基因表达的相关性.结果:生物信息学分析和定量PCR结果显示GABRP基因在三阴性乳腺癌(triple negative breast cancer,TNBC)及BLTNBC中显著性高表达(p＜0.05);在non-TNBC,TNBC,BLTNBC中,其表达与细胞增殖、HER-2表达无明显相关性(P＞0.05),而在BLTNBC中与淋巴结转移状态有明显相关性(P＜0.05),在non-TNBC巾与ER表达有明显相关性(P＜0.05).结论:GABRP基因可作为BLTNBC的有潜力的预后诊断分子标志物.     

Fine‐needle aspiration cytology of triple‐negative basal‐like breast cancer

Invasive breast cancer is divided into luminal A, luminal B, HER2 overexpression, basal‐like (BL) and normal‐like subtypes, among which the BL subtype has the worst prognosis. The purpose of this study was to determine the clinicopathological and cytological characteristics of BL breast cancer (BLBC). Fine‐needle aspiration cytology samples from 17 patients with consecutive BLBC were investigated, and the findings were compared with those of other subtypes (10 cases each) for the following cytomorphological features: necrosis; lymphocyte infiltration; mitotic index; apoptosis; naked nuclei; nuclear/cytoplasmic ratio; nuclear margin, size and pleomorphism; chromatin granularity and density; and nucleolar appearance. Histologically, the BLBCs were heterogeneous, and included medullary carcinoma and metaplastic carcinoma, in addition to invasive ductal carcinoma. Cytologically, high mitotic index, naked nuclei, and irregular nuclear margin were significantly observed when compared with both the luminal A and B subtypes. Large nuclei with nucleoli and lymphocyte infiltration were frequently seen compared with the luminal A and B subtypes, respectively. Squamous nodules were seen in all metaplastic cases, but not in the HER2 overexpression subtype. Lymphocyte infiltration, squamous metaplasia, and nuclear findings such as a high mitotic index, naked or large nuclei, an irregular nuclear margin and the presence of nucleoli, may be clues indicating BLBC. Diagn. Cytopathol. 2013;41:283–287. © 2011 Wiley Periodicals, Inc.     

Characterization of basal-like breast cancer: an update

Basal-like breast cancers express genes and proteins associated with the basal layer of mammary epithelium and account for 10-25% of breast cancers. These tumours are of particular interest because they follow an aggressive clinical course and currently lack any form of standard targeted systemic therapy. Over recent years, numerous studies have sought to further characterize this sub-group and dissect out the molecular features that define them. Several biomarkers represent credible novel therapeutic targets and can be evaluated using routine laboratory techniques. As such the basal-like sub-type is becoming increasingly relevant to the histopathologist. However, since recognition of this sub-type is not part of the minimum dataset for breast cancer reporting, many will be unfamiliar with diagnosing these lesions. In this paper, we review the key characteristics of basal-like cancers, discuss closely related entities (triple negative and hereditary breast cancer), and consider the role of molecular markers implicated in these tumours.     

The combination of high cyclin E and Skp2 expression in breast cancer is associated with a poor prognosis and the basal phenotype

Gene expression studies have identified a basal phenotype of breast cancer; these are hormone receptor and HER2-negative cancers with poor prognosis. High levels of cyclin E and Skp2, and low levels of p27 have previously been individually associated with both basal-like breast cancer and a poor outcome after diagnosis. The goal of this study was to first confirm the prognostic value of these biomolecular markers using a breast cancer tissue microarray. Second, we also test the hypothesis that the combined phenotype of high cyclin E, low p27, and high Skp2 would be a strong predictor of outcome and would be closely associated with the basal phenotype of breast cancer. Our cohort consisted of 438 cases of breast cancer and the median follow-up was 15.4 years. The tissue microarray was constructed from archival tumor blocks and we used commercially available antibodies for biomarker immunostaining. Cyclin E was positive in 46% of cases, p27 was negative in 62%, and Skp2 was positive in 35%. We found cyclin E and Skp2 to be prognostic for breast cancer-specific survival in univariate analyses, but p27 was not prognostic. The strongest predictor of outcome was the combination of cyclin E positive and Skp2 positive (difference in survival of 19% at 10 years, P = .0009). This combination was present in 78 (27%) of 288 cases for which data on both biomarkers were available. This combination was also highly associated with young age at diagnosis, grade 3 tumors, ER-negative status, HER2-negative status, and the basal biomarkers epidermal growth factor receptor and cytokeratin 5/6. However, in a multivariate model including standard clinicopathologic variables, this combination was not found to have independent prognostic significance. In conclusion, the combination of high cyclin E and Skp2 expression predicts for poor prognosis in breast cancer in univariate analysis only, it is associated with high risk features, and it is associated with the basal phenotype.     

CD109 expression in basal-like breast carcinoma

Breast cancer can be classified into several subtypes based on gene expression profiling. Basal-like breast carcinoma (BLC) has a triple negative phenotype, that is, the subtype lacks the estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2). It has been recently reported that CD109, a glycosylphosphatidylinositol (GPI)-anchored cell surface protein, is a new breast myoepithelial marker. In the present study CD109 expression was investigated in invasive ductal carcinomas (IDC) of the breast on immunohistochemistry. Eighty-eight formalin-fixed, paraffin-embedded breast carcinoma sections were immunostained with anti-CD109, anti-cytokeratin 5/6 (CK5/6), anti-calponin, anti-vimentin and anti-p63 antibodies. CD109 expression was detected in 18 of 30 basal-like breast carcinomas (BLC) but not in other types of 53 IDC (non-BLC) that were positive for ER, PgR and/or HER2. The percentage of CD109-positive tissues (60%) in BLC was similar to that of CK5/6 (63%) and higher than that of other myoepithelial markers including p63 (23%), calponin (33%) and vimentin (33%). Statistical analysis indicated that the CD109-positive group in BLC, but not the CK5/6-positive group in BLC, was associated with reduced fat invasion ( P  < 0.05). These findings indicate that CD109 is a useful diagnostic marker for BLC and that CD109 expression may affect biological properties of cancer cells.     

p63 correlates with both BRCA1 and cytokeratin 5 in invasive breast carcinomas: further evidence for the pathogenesis of the basal phenotype of breast cancer

AIMS: To study the expression of p63, cytokeratin (CK) 5 and CK8/18 in invasive ductal carcinomas and their relationship with BRCA1 and other pathological and immunohistochemical features of clinical significance. METHODS AND RESULTS: Immunohistochemistry with the antibodies p63, CK5, CK8/18, BRCA1, oestrogen receptor, progesterone receptor, p53, c-erbB-2 and Ki67 was performed in 102 formalin-fixed paraffin-embedded samples of invasive ductal carcinomas. The CK5+ cases were submitted to a double-immunolabelling study with p63. There was a strong relationship between CK5 and p63 expression and both markers were associated with hormonal receptor-negative high-grade carcinomas with high proliferative rate. Furthermore, there was coexpression of CK5 and p63 in neoplastic cells, indicating that p63, like CK5, is a marker of the basal phenotype of breast cancer. There was a strong relationship between reduced expression of BRCA1 with both p63 and CK5 expression as well as an inverse correlation between p63 and CK8/18 expression, suggesting that loss of p63 expression is required for the transition between a basal to a luminal phenotype of breast carcinoma. CONCLUSIONS: Since p63 is thought to be a marker of stem cells and may act as an oncogene, our data support the idea that BRCA1 acts as stem cell regulator.