Xiaobo Zhu

Patterns of cancer invasion revealed by QDs-based quantitative multiplexed imaging of tumor microenvironment

Tumor growth and progression depends on their microenvironment, which undergoes constant co-evolution because of the dynamic tumor-stormal interactions. Such co-evolution has long been under appreciated due to the lack of appropriate technology platforms to simultaneously reveal these complex interactions. Here we report on a quantum dots based multiplexed imaging and spectrum analysis technology to simultaneously study major components of tumor stroma, including type IV collagen, tumor angiogenesis, macrophages infiltration and tissue destructive proteolytic enzyme matrix metalloproteinase 9. The new technology revealed a panoramic picture of the tempo-spatial co-evolution of tumor cells and their stroma at the architecture level. Four patterns of tumor invasion with distinctive co-evolution features were identified as Washing pattern, Ameba-like pattern, Polarity pattern and Linear pattern. This quantum dots based multiplexed technology could help gain new insight into the complex process of tumor invasion, and formulate new anti-cancer strategies.

Quantum-dot-based immunofluorescent imaging of HER2 and ER provides new insights into breast cancer heterogeneity

Breast cancer (BC) is a heterogeneous tumor, and better understanding of its heterogeneity is essential to improving treatment effect. Quantum dot (QD)-based immunofluorescent nanotechnology (QD-IHC) for molecular pathology has potential advantages in delineating tumor heterogeneity. This potential is explored in this paper by QD-IHC imaging of HER2 and ER. BC heterogeneity can be displayed more clearly and sensitively by QD-IHC than conventional IHC in BC tissue microarrays. Furthermore, the simultaneous imaging of ER and HER2 might help understand their interactions during the process of evolution of heterogeneous BC.

Comparison of quantum dots immunofluorescence histochemistry and conventional immunohistochemistry for the detection of caveolin-1 and PCNA in the lung cancer tissue microarray.

Luminescent semiconductor quantum dots (QDs) are a new class of fluorescent label with wide ranges of applications in cell imaging. In this study, we evaluated the capability of QDs immunofluorescence histochemistry (QDs-IHC) for detecting antigens of caveolin-1 and PCNA in the lung cancer tissue microarray (TMA) in comparison with the conventional immunohistochemistry (IHC) technique. Both methods revealed consistent antigen localization and statistically non-significant detection rates of caveolin-1 and PCNA expressions in our study. However, the sensitivity of QDs-IHC was higher than IHC. The positive detection rates of caveolin-1 and PCNA by QDs-IHC were 57% (40/70) and 86% (60/70), respectively, which were higher than the detection rates of 47% (33/70) and 77% (54/70), respectively, by IHC. Moreover, QDs exhibited a much better photostability, a broader excitation spectrum and a longer fluorescence lifetime. We showed here the advantages of QDs-IHC over IHC for the detection of caveolin-1 and PCNA in lung cancer TMA.

Quantum dot-based quantitative immunofluorescence detection and spectrum analysis of epidermal growth factor receptor in breast cancer tissue arrays

Background The epidermal growth factor receptor (EGFR) is a promising therapeutic target in cancer, but its clinical value in breast cancer remains controversial. Our previous studies have found that quantitative analysis of biomarkers with quantum dot-based nanotechnology had better detection performance than conventional immunohistochemistry. The present study was undertaken to investigate the prognostic value of EGFR in breast cancer using quantum dot-based quantitative spectral analysis. Methods EGFR expression in 65 breast cancer specimens was detected by immunohistochemistry and quantum dot-immunohistochemistry, and comparisons were made between the two methods. EGFR expression in tissue microarrays of 240 breast cancer patients was then detected by quantum dot-immunohistochemistry and spectral analysis. The prognostic value of EGFR immunofluorescence area (EGFR area) for five-year recurrence-free survival was investigated. Results The same antigen localization, high correlation of staining rates (r = 0.914), and high agreement of measurement (κ = 0.848) of EGFR expression in breast cancer were found by quantum dot-immunohistochemistry and immunohistochemistry. The EGFR area showed significant differences by tumor grade, lymph node status, HER2 status, and hormone receptor status (all P < 0.05). Patients in the large EGFR area (≥30.51) group had a significantly higher five-year recurrence rate (47.2% versus 27.4%, P = 0.002) and worse five-year recurrence-free survival (log-rank test, P = 0.0015) than those in the small EGFR area (<30.51) group. In the subgroups, EGFR area was an independent prognosticator in the HER2-positive and lymph node-positive subgroups. Conclusion Quantum dot-based quantitative detection demonstrates the prognostic value of EGFR area in the HER2-positive and lymph node-positive subgroups of invasive breast cancer.

Detection of EBV in nasopharyngeal carcinoma by quantum dot fluorescent in situ hybridization

AIMS Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia and is frequently associated with Epstein-Barr virus (EBV) infection. The primary aim of this study was to improve the method of EBV detection by exploring quantum dots in FISH detection, and compare QD-based FISH with conventional ISH. MATERIALS AND METHODS Biopsy specimens were retrospectively retrieved from 35 NPC patients as paraffin-embedded tissue blocks. QD-FISH was developed to detect the presence of EBV encoded small RNA (EBER) using biotin-labeled EBER oligonucleotide probe indirectly labeled with streptavidin-conjugated quantum dots. Conventional ISH was also performed using a commercial kit to assess concordance between the two methods. RESULTS All the 35 NPC cases were nonkeratinizing carcinoma (7 differentiated and 28 undifferentiated subtypes). EBER-positive signals were detected in 91.43% (32/35) and 80% (28/35) cases by QD-FISH and ISH, respectively. There was no significant difference in the number of EBER-positive cases by the two methods. A moderate concordance was found between QD-FISH and ISH for EBER status (κ=0.55). Four EBER-negative cases by ISH showed EBER-positive signals when detected by QD-FISH. CONCLUSIONS EBV is closely associated with NPC in Chinese patients. QD-FISH is a novel effective method for EBER detection, and has a moderate concordance with conventional ISH.