[Show abstract][Hide abstract] ABSTRACT: Breast cancer is the leading cause of cancer death in females worldwide, and the majority type is infiltrating ductal carcinoma (IDC). Most of IDC patients died of metastasis and recurrence. Cancer stem cells (CSCs) are defined with the ability to be self-renewal and potentially promote proliferation and formation of tumors. CSCs are related to angiogenesis and are important targets in new cancer treatment strategies. In this study, we purposed to investigate on expression and clinical significances of CSCs marked by CD133 and CD44 in IDC and their relationship to angiogenesis.
The specimens of IDC from 325 Chinese patients with follow-up were analyzed for CD133, CD44, CD82, and CD34 protein expression by immunohistochemical staining. The Pearson chi-square test and t test were used to assess the associations among the positive staining of these markers and clinicopathological characteristics. Postoperative overall survival time in these patients with IDC was analyzed by univariate and multivariate analyses.
In IDC tissues, positive rates of 48.6%, 53.8%, and 42.2% were obtained for CD133, CD44, and CD82 protein, respectively; the mean score of microvessel density (MVD) was 20.5 ± 7.0 in IDC group. And there was a significant difference between the two groups. There was a positive relationship between the expression of CD133, CD44, and the score of MVD and the grades of tumor, lymph node metastasis, tumor-node-metastasis (TNM) stages (all P < 0.05); and the expression of CD82 was negatively related to grades of tumor, lymph node metastasis, and TNM stages (all P < 0.05). The overall mean survival time of the patients with CD133, CD44, and the score of MVD (≥21) positive expression was lower than that of patients with negative expression. The overall mean survival time of patients of CD82-positive expression was longer than that of patients of the negative expression group. The positive expression of CD133 and CD82, and TNM stages were independent prognostic factors of IDC (P < 0.05).
CSCs, angiogenesis, and aberrant expression of CD82 may be involved in the initiation, development, metastasis, and recurrence. It is suggested that CSCs, angiogenesis, and CD82 be possible as a therapeutic marker for anti-tumor therapy.
Preview · Article · Dec 2015 · World Journal of Surgical Oncology
[Show abstract][Hide abstract] ABSTRACT: Centrally necrotizing carcinoma of the breast (CNC) represents a newly-identified subset of breast cancer. The clinical and pathological characteristics of this breast cancer subtype are not yet completely understood.
We assessed the clinicopathological characteristics of 73 cases of CNC and 30 control cases of high-grade infiltrating ductal carcinoma (IDC) with focal necrosis based on light microscopy and immunohistochemical staining for estrogen receptor, progesterone receptor, Cerb-B2/HER2, Ki-67, epidermal growth factor receptor, cytokeratin 5/6, smooth muscle actin, S-100 protein, p63 and CD10.
All the tumors showed extensive central necrotic or acellular zones with different degrees of fibrotic or hyaline material surrounded by ring-like or ribbon-like residual tumour tissue which were usually high-grade IDCs. The central necrotic zone accounted for at least 30% of the cross-sectional area of the tumor. Thirty-six cases (49.3%) showed a component of ductal carcinoma in situ. The tumorous stroma around the central necrotic zone was accompanied by myxoid matrix formation in 28 cases (40%). Lymphocytic infiltration was present in 53 cases (72.6%). Granulomatous reactions were detected at the periphery of the tumors in 49 cases (67.1%). Immunohistochemistry showed greater expression of basal-like markers (72.2%, 52 cases) than myoepithelial markers (60.6%, 43 cases), both of which were significantly higher than in controls (26.7%, 8 cases) (P < 0.001). According to molecular typing, most CNCs were basal-like subtype (37 cases, 50.7%). Follow-up data were available for 28 patients. Disease progression occurred in 11 patients. The combined rate of recurrence, distant metastasis or death was significantly higher in CNC patients compared with controls (P < 0.05).
CNC was associated with distinctive clinicopathologic features mostly characterized as basal-like type. Its high proliferative activity, highly-aggressive biological behavior, and high rates of recurrence and metastasis, suggest that CNC should be classified as a new type of breast carcinoma.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate KAI1/CD82 protein expression in human nasopharyngeal carcinoma (NPC) cell lines and human NPC tissues. Immunohistochemistry and western blot analysis were used to detect the localization and expression levels of the KAI1/CD82 protein in five human NPC cell lines. Immunohistochemistry was also conducted to detect the expression of the KAI1/CD82 protein in 70 NPC tissues and 30 non-neoplastic nasopharyngeal tissues. The levels of KAI1/CD82 protein expression were found to decrease as the metastatic potential of cells increased. The expression rate of KAI1/CD82 protein in the NPC tissues (44.3%) was significantly lower than that in the non-neoplastic nasopharyngeal tissues (70.0%) (P<0.05). KAI1/CD82 protein expression in the NPC tissues was not associated with clinical parameters, including gender, age, histological type and T stage, and the positive expression of KAI1/CD82 decreased with increased N staging. The level of KAI1/CD82 protein expression was increased in different human NPC cell lines. The KAI1/CD82 gene was highly expressed in cells with low metastatic potential, while low expression was observed in cells with a high metastatic potential. In addition, the KAI1/CD82 gene was expressed at low levels in nasopharyngeal carcinoma tissues, while high expression was identified in non-neoplastic nasopharyngeal tissues, and was associated with lymph node metastasis. These results indicated that the KAI1/CD82 gene may be involved in the occurrence, development and metastasis of nasopharyngeal carcinoma.
[Show abstract][Hide abstract] ABSTRACT: The present paper aims to investigate whether or not vasculogenic mimicry (VM) exists in laryngeal squamous cell carcinoma (LSCC), and to elucidate its relationship to microvessel density (MVD), galectin-3 (Gal-3) expressionb and clinicopathological factors of patients with LSCC. VM, score of MVD and expression of Gal-3 protein were detected by immunohistochemistry and histochemistry in 83 specimens of LSCC tissue and 20 specimens of nor- mal laryngeal tissue. The positive rate of VM in normal laryngeal tissues was 0%, and was 33.7% in LSCC tissues. There was a significant difference between the two groups (P<0. 01). VM or MVD was significantly related to differentiation, pTNM stages and lymph node metastasis of LSCC (P<0.05), but not to age, gender and tumor site (P>0. 05). And there was a positive correlation between every two of VM, score of MVD, and Gal-3 protein (P< 0. 05). The results suggest that expression of Gal-3 protein may be related to the initiation, angiogenesis and VM formation in LSCC; And VM, angiogenesis and Gal-3 protein may be involved in the development, invasion and metastasis of LSCC.
No preview · Article · Aug 2014 · Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi
[Show abstract][Hide abstract] ABSTRACT: Background
To investigate on expressions and clinical significances of CD133 protein and vasculogenic mimicry (VM) in primary non-small cell lung cancer (NSCLC).
The specimens of NSCLC from 305 Chinese patients with follow-up were analyzed for CD133 protein expression and VM by immunohistochemical and histochemical staining.
In NSCLC, positive rates of 48.9% and 35.7% were obtained for CD133 and VM, respectively. The VM and expression of CD133 were significantly higher in carcinoma than in normal. There were a positive relationship between the VM and expression of CD133 and the tumor grade, lymph node metastasis and clinical stage (all P<0.05). The overall mean survival time of the patients with CD133 and VM positive expression was lower than that of patients with negative expression. Microvessel density (MVD) was positive corresponded with the grade, lymph node metastasis and clinical stage (all P<0.05). The overall mean survival time of the patients with MVD≥22’s group was shorter than that of patients with MVD<22’s group. Pathological-tumor-node-metastasis (pTNM) stage, positive expression of CD133 and VM, postoperative therapy and MVD were independent prognostic factors of NSCLC (P<0.05). Immunohistochemistry revealed an important intratumoral heterogeneity in all four CD133 expression profiles.
VM, MVD and expression of CD133 are related to differentiation, lymph node metastasis, clinical stage, and prognosis. It is suggested that CD133, VM and MVD should be considered as a potential marker for the prognosis.
[Show abstract][Hide abstract] ABSTRACT: In recent years, many studies have revealed the prognosis in patients with non-small cell lung cancer (NSCLC). In general, some clinic-pathological parameters have been related with prognosis. The aim of this study is to detect the relationship among lymphatic vessel density (LVD), microvessel density (MVD), expression of carcinoembryonic antigen (CEA) mRNA, metastasis suppressor genes (KAI1 and Kiss-1), and the prognosis of NSCLC patients.
Blood samples were collected from 57 cases of NSCLC. The transcription of CEA mRNA was detected via nested reverse transcriptase-polymerase chain reaction and micro-fluid chip. Immunohistochemistry was performed to detect the expression of LVD, MVD, KAI1 and Kiss-1 in the patients. All follow-up data were collected and analyzed.
The overall five-year survival rate was 18%, and the median survival was 34 months. TNM stage, lymph node metastasis, and expression of MVD, LVD, CEA mRNA and Kiss-1 were factors to survival, as determined via single survival analysis. Multivariate analysis demonstrated that TNM stage, lymph node metastasis, and expression of CEA mRNA were independent prognostic factors for NSCLC patients.
The expression of MVD, LVD, Kiss-1 and CEA mRNA is related to the prognosis of NSCLC.
No preview · Article · Jun 2012 · Zhongguo fei ai za zhi = Chinese journal of lung cancer
[Show abstract][Hide abstract] ABSTRACT: Maspin belongs to the serine protease inhibitor (serpin) family and has been proven to be a suppressor of tumor growth and metastasis in many types of tumors. The purpose of this study was to investigate the expression of maspin in non-small cell lung cancer (NSCLC) and its relationship to vasculogenic mimicry (VM). A total of 160 specimens of NSCLC were involved in this study and 20 specimens of normal lung tissue served as controls. VM, microvessel density (MVD) and the expression of maspin were detected by using immunohistochemical staining. The results showed that the positive rates of maspin and VM in the NSCLC group were 48.1% (77/160) and 36.9% (59/160), respectively, which were significantly different from those in the control group with the positive rates of maspin and VM being 100% and 0% respectively (P<0.05). VM, MVD and the expression level of maspin were significantly related to tumor differentiation, lymph node metastasis, clinical stages and postoperative survival time (all P<0.05). The maspin expression in patients with squamous cell carcinoma was significantly higher than that in those with adenocarcinoma (P<0.05). The maspin expression was negatively correlated with VM and MVD, and there was a positive correlation between VM and MVD. Maspin-negative expression, VM and high MVD score were negatively related to the 5-year-survival rate. PTNM stages, VM, MVD and maspin expression were independent prognostic factors for NSCLC (P<0.05). It was suggested that the loss of expression of maspin may participate in the invasion and metastasis of NSCLC and it has a positive relationship to VM in NSCLC. Combined detection of maspin, VM and MVD may help predict the progression and prognosis of NSCLC.
No preview · Article · Jun 2012 · Journal of Huazhong University of Science and Technology
[Show abstract][Hide abstract] ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is a predominant type of esophageal cancer, which is a malignant tumor originating from the esophageal mucosa or gland and is aggressive with poor prognosis. Identification of new gene expression patterns would be helpful for providing new targets for the early detection and treatment of ESCC patients. In the present study, we employed cDNA array technology to compare gene expression profiles between ESCC tissues and adjacent normal epithelial tissues from ESCC patients. There was at least a 4-fold change in the expression levels of 72 genes that were significantly increased and 107 genes that were decreased in ESCC compared with normal esophageal epithelium. Among them, genes known to be involved in ESCC were found, including matrix metalloproteinases, transcription factors SOX-4 and SOX-17, the Wingless-type MMTV integration site family member 2, and cell cycle regulators. Moreover, we have newly identified the two genes that are down-regulated in ESCC: monoamine oxidase A, an enzyme that catalyzes monoamines oxidation and 15-hydroxyprostaglandin dehydrogenase [NAD+], a prostaglandin-synthesizing enzyme that physiologically antagonizes COX-2. Likewise, we found the three genes that are up-regulated in ESCC: CD7, a cell surface glycoprotein member of the immunoglobulin superfamily, LIM-domain kinase 1, a small subfamily with an unique combination of two N-terminal LIM motifs and a C-terminal protein kinase domain, and TTK protein kinase, a previously unidentified member of the kinase family. These newly identified genes may be involved in the progression of the tumor and/or represent properties specific to ESCC.
No preview · Article · Apr 2012 · The Tohoku Journal of Experimental Medicine
[Show abstract][Hide abstract] ABSTRACT: Vasculogenic mimicry (VM), found in many high invasive ability tumors, is associated with tumor invasion and metastasis. Many genes exhibit abnormal levels of expression in these tumors. This study aims to find good markers for predicting the invasion and metastasis of non-small cell lung cancer (NSCLC).
VM and expression of CD82/KAI1 and HIF-1α were examined via immunohistochemistry and histochemistry of 160 NSCLC and 20 normal lung tissue specimens.
In NSCLC, positive rates of 37.5%, 48.8%, and 36.9% were obtained for CD82/KAI1, HIF-1α, and VM, respectively. In normal lung tissue, positive rates of 95.0%, 0, and 0 were obtained for CD82/KAI1, HIF-1α, and VM, respectively. A significant difference was found between the NSCLC and normal lung groups (P<0.01). VM and the expression levels of CD82/KAI1 and HIF-1α were significantly related to tumor differentiation, lymph node metastasis, clinical staging, and postoperative survival time (P<0.01 for all). A negative correlation was found between the expression levels of CD82/KAI1 and HIF-1α; a similar relationship was observed between CD82/KAI1 and VM. A positive relationship between the expression of HIF-1α and VM was revealed; there was a significant relationship between microvessel density (MVD) and the expression of CD82/KAI1 or HIF-1α or VM. VM and overexpression of HIF-1α were related to poor prognosis: the survival rates were significantly lower in positive patients than in negative patients (both P<0.01). The survival rates of the CD82/KAI1-positive and CD82/KAI1-negative groups were significantly different (P<0.01). The five-year survival rate was significantly different between the group with MVD≥22 and the group with MVD<22 (P<0.01). pTNM stage, positive expressions of CD82/KAI1 and HIF-1α, and VM were independent prognostic factors of NSCLC (P<0.01).
VM and the expressions of CD82/KAI1 and HIF-1α in NSCLC are related to differentiation, lymph node metastasis, clinical staging, and prognosis. The combined detection of CD82/KAI1, HIF-1α, and VM has an important role in predicting the progression and prognosis of NSCLC.
No preview · Article · Dec 2011 · Zhongguo fei ai za zhi = Chinese journal of lung cancer