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Tse G.M.,Chinese University of Hong Kong | Ni Y.-B.,Chinese University of Hong Kong | Tsang J.Y.S.,Chinese University of Hong Kong | Shao M.-M.,Guangzhou University | And 5 more authors.
Histopathology | Year: 2014

Aims: Many immunohistochemical markers have been studied for differentiating papillary lesions. However, their differentiating power has not been evaluated comprehensively. Additionally, assessment of some markers will require the difficult task of identifying different cell types. In the current study, we aimed to devise a simple papillary panel which can aid in diagnosis irrespective of architectural pattern and cell type differentiation. Methods and results: Immunohistochemical analysis of papillary lesions using myoepithelial markers [p63 and smooth muscle actin (SMA)], high molecular weight cytokeratins (HMWCKs: CK5, CK5/6, CK14 and 34βE12), hormone receptors (ER and PR) and neuroendocrine markers (chromogranin and synaptophysin) was performed. Among them, neuroendocrine markers showed high specificity but low sensitivity. HMWCK specificity was better than that for myoepithelial markers. Homogeneous staining pattern for hormonal receptors rather than their percentage positivity was more effective in identifying malignant lesions. Negative staining for two or more of HMWCKs, namely CK5/6, CK14 and 34βE12, achieved the best overall specificity and sensitivity of 87.8% and 94.1%, respectively, irrespective of the architecture. Their discriminatory power was validated with an independent cohort of core needle biopsies. Conclusions: A marker panel with HMWCKs could be used in differentiating papillary lesions irrespective of architectural pattern or cell type differentiation. © 2014 John Wiley & Sons Ltd.

Luo M.-H.,Peking University | Huang Y.-H.,Shenzhen Second People Hospital | Ni Y.-B.,Chinese University of Hong Kong | Tsang J.Y.S.,Chinese University of Hong Kong | And 3 more authors.
Human Pathology | Year: 2013

Immunohistochemical analysis of gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin (MGB) is frequently used in routine practice for assessment of metastases or regional recurrences of breast origin. Breast cancer is highly heterogeneous. Expression of these 2 markers in various breast cancer subtypes has not been well studied. In addition, the usefulness of these two markers in combination in detecting breast origin has not been explored. In this study, a large cohort of breast cancers was evaluated for GCDFP-15 and MGB expression, both individually and combined. Their expression was correlated with cancer subtypes, other biomarkers and clinicopathologic parameters. A higher sensitivity for MGB (42.3%) than GCDFP-15 (31.6%) in detecting cancers of breast origin was observed. Combining both increased the sensitivity further, both for primary tumor (53.0%) and for nodal metastases (69.0%). GCDFP-15 was associated significantly with a breast cancer profile of good prognosis tumors, including lower grade (P <.001), pN (P =.029) and Ki-67 (P <.001) as well as negative basal markers expression (P =.043,.009, and.049 for c-Kit, CK5/6 and epidermal growth factor receptor, respectively) and, thus, may not be sensitive for detection of poor prognosis tumors. MGB has the highest expression in HER2-overexpressing cancers (56.6%), and may be a potentially useful marker for this subtype. Nonetheless, both markers showed low expression in the basal like (BLBC) subtype (11.9% and 21.4% for GCDFP-15 and MGB respectively), therefore, the detection of BLBC remains problematic. Negative results need to be interpreted with caution, and correlation with other clinical findings may be required to exclude the possibility of metastatic BLBC. © 2013 Elsevier Inc.

Huang Y.-H.,Shenzhen Second People Hospital | Luo M.-H.,Peking University | Ni Y.-B.,Chinese University of Hong Kong | Tsang J.Y.S.,Chinese University of Hong Kong | And 5 more authors.
Histopathology | Year: 2014

Aims: SOX2 is a key regulatory gene in embryonic stem cells. Although it has been implicated in cancer progression, its role in breast carcinoma is poorly understood. Materials and methods: Fifty-seven ductal carcinomas in situ (DCIS), 552 invasive breast carcinomas and 107 corresponding metastatic lymph nodes were evaluated immunohistochemically for the expression of SOX2. Its correlation with clinicopathological features, other biomarker profiles and patients' outcomes were analysed. Results: SOX2 was detected in 19.0% (105 of 552) of invasive breast carcinomas and 12.3% (seven of 57) of DCIS. Expression correlated with larger tumour size (P = 0.005) and higher grade (P = 0.002). It was associated negatively with ER (P = 0.015) and PR (P = 0.046) expression, but positively with Ki67 index (P = 0.013). Interestingly, it was also associated with neuroendocrine marker expression (synpatophysin and chromogranin/synaptophysin, P = 0.048 and 0.028, respectively). Expression appeared to be independent from that of common stem cell markers, namely CD44, CD24 and aldehyde dehydrogenase 1 (ALDH1). Furthermore, a higher rate of expression was observed in metastatic lymph nodes than in the corresponding primary tumours (P = 0.034). High SOX2 expression was correlated with poor disease-free survival (log-rank=9.489, P = 0.012) and was an independent prognostic factor (HR=2.918, P = 0.015) in patients with high nodal stages. Conclusions: In summary, SOX2 expression was related to adverse breast carcinoma profile and poor outcome in selected patient groups. © 2013 John Wiley & Sons Ltd.

Tsang J.Y.S.,Chinese University of Hong Kong | Huang Y.-H.,Shenzhen Second People Hospital | Luo M.-H.,Peking University | Ni Y.-B.,Chinese University of Hong Kong | And 5 more authors.
Breast Cancer Research and Treatment | Year: 2012

Cumulative evidence has demonstrated the presence of cancer stem cells (CSC) in breast cancer and its putative role in cancer progression. Nonetheless, the clinical significance of CSC in breast cancer remains elusive. The underlying reasons could be due to the heterogeneity of breast cancer subtypes as well as different markers used to define breast CSC. In this study, three widely used markers (aldehyde dehydrogenase (ALDH)1? and CD24-CD44?) were used to define two populations of CSC in a large cohort of breast cancers. The expressions of these markers were correlated with different clinicopathological features and the molecular subtypes. ALDH1? breast cancers were associated with basal-like and HER2-overexpressing subtypes and the characteristics histologic features were related to these two subtypes. On the other hand, CD24-CD44? breast cancers were associated positively with the presence of extensive in situ component, the absence of lymph node involvement, and basal markers, but negatively with HER2. CD24-CD44? breast cancers were also positively associated with luminal B cancers. As the expression of CSC markers varied among different molecular subtypes and different clinicopathological features, it appeared that each CSC population could have distinct clinical values in different subgroups of breast cancers. For improved prognostication with CSC, combining the analysis of CSC markers would be required. Within the luminal cancers, CSC appeared to identify cancers with poor outcome. The presence of CSC populations was associated with ER-PR? cancers and tumors expressing basal markers. Basal marker expression can complement with CSC for improved indicator for poor prognosis in luminal breast cancers. For the first time, the possible contribution of CSC to these aggressive luminal cancers was demonstrated. The association of basal features and CSC in luminal cancers also raised the possibility that luminal cancer cells may acquire basal phenotype and CSC properties together during their progression. © Springer Science+Business Media New York 2012.

Zhu W.,Guangzhou University | Zhu W.,Shenzhen Tissue Engineering Laboratory | Huang J.,Shenzhen Tissue Engineering Laboratory | Lu W.,Shenzhen Second People Hospital | And 9 more authors.
Artificial Cells, Nanomedicine and Biotechnology | Year: 2014

Objective: By in situ polymerization of poly-L-lactic acid (PLLA) and nano-hydroxyapatite (Nano-HA), and finding the best proportion of composite, so as to get ideal interface fixation material. Methods: According to a certain ratio (the mass fraction of Nano-HA, respectively, is 0%, 10%, 20%, 30% and 40%), composite PLLA and Nano-HA by in situ polymerization, and test the performance of this kind of new type of interface fixation such as, bending strength,compressive strength, elastic modulus, scanning electron microscopy (SEM) and degradation experiments in vitro. Then observe its mechanical properties, microstructure, the dispersion of Nano-HA in the PLLA and degradation rate of composite materials. Results: 1. Mechanical tests show that with the increase of Nano-HA content, the tensile strength decreases and the elastic modulus increases; with Nano-HA content of 20%, the bending strength of composite materials presents the peak value (156.8 MPa). 2. SEM scan shows the fracture surface of pure PLLA is relatively smooth; with Nano-HA content of 10%, the fracture surface shows a large number of dimples, and is obvious rough; with Nano-HA content of 20%, the fracture surface is uneven, forming a large number of dimples; with Nano-HA content of 30% or more, the fracture surface becomes more flat, and there are some small dimples. 3. Degradation experiments in vitro show the following: as the degradation time goes on, the pH values of degradation liquid is gradually reduced and the mechanical properties of composite materials also gradually have some decay. Conclusion: With Nano-HA content of 20%, the interface fixation material has a better mechanical properties and degradation properties. According to the best ratio, prepare Nano-HA/PLLA composite artificial materials with good performance. © 2014 Informa Healthcare USA, Inc.

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