Bone is one of the most metastatic sites of advanced malignant tumors. With the continuous improvement of diagnosis and treatment of malignant tumors, the survival time of patients is prolonged and incidence of bone metastases also increases. Lung cancer is the leading cause of cancer-related mortality worldwide. It is estimated that the incidence of bone metastases in patients advanced lung cancer is about 30%-40%. The traditional diagnosis of bone metastases in lung cancer is based on clinical symptoms, X ray, computed tomography (CT), magnetic resonance imaging (MRI) and pathology. Recently, a large number of exploratory studies have reported blood biomarkers as indicators of bone metastasis screening and efficacy evaluation. In this review, we summarize the progress of biomarkers in diagnosis of bone metastases of lung cancer.
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Biomarkers, Tumor ; metabolism ; Bone Neoplasms ; metabolism ; physiopathology ; secondary ; Humans ; Lung Neoplasms ; pathology ; Osteogenesis

Granulocyte-colony stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation and maturation of precursor cells in the bone marrow into fully differentiated neutrophils. Several reports of G-CSF-producing malignant tumors have been published, but scarcely any in the hepatobiliary system, such as in hepatocellular carcinoma (HCC). Here, we encountered a 69-yr-old man with a hepatic tumor who had received right hepatic resection. He showed leukocytosis of 25,450/microL along with elevated serum G-CSF. Histological examination of surgical samples demonstrated immunohistochemical staining for G-CSF, but not for G-CSF receptor. The patient survived without recurrence for four years, but ultimately passed away with multiple bone metastases. In light of the above, clinicians may consider G-CSF-producing HCC when encountering patients with leukocytosis and a hepatic tumor. More cases are needed to clarify the clinical picture of G-CSF-producing HCC.
Aged ; Bone Neoplasms/secondary ; Carcinoma, Hepatocellular/*metabolism/pathology ; Fatal Outcome ; Granulocyte Colony-Stimulating Factor/*metabolism ; Humans ; Liver Neoplasms/*metabolism/pathology ; Male ; Receptors, Granulocyte Colony-Stimulating Factor/metabolism

OBJECTIVETo determine how patients with infiltrating lobular carcinoma (ILC) differ from patients with the more common infiltrating ductal carcinoma (IDC), and observe the different expression patterns of E-cadherin and p120-catenin proteins in both ILCs and IDCs.

METHODSThe patients with ILC admitted to our hospital from Jan 1999 to Dec 2006 and patients with IDC from Jan 2000 to Dec 2000 were included in this study. All their pathological slides were reviewed, and their clinical data and treatment variables were analyzed retrospectively. Then the expression patterns of E-cadherin and p120-catenin proteins in both ILCs and IDCs were detected by immunohistochemistry on tissue microarray.

RESULTSThe 5-year overall survival was 81.7% for ILCs and 79.1% for IDCs (P = 0.055). The 5-year disease-free survival was 61.8% for ILCs and 83.7% for IDCs (P < 0.001). Cytoplasmic localization of p120-catenin and loss of E-cadherin expression were more common in ILCs than in IDCs. The complete losses of E-cadherin in ILCs and IDCs were 55.6% (20/36) and 20.4% (45/221, P < 0.001), respectively. The p120-catenin showed a diffuse cytoplasmic localization in 66.7% (24/36) of ILCs and 16.3% (36/221) of IDCs (P < 0.001). Interestingly, the cytoplasmic localization of p120-catenin was clearly associated with the absence of E-cadherin expression in ILCs (P = 0.002), cytoplasmic localization of p120-catenin and absence of E-cadherin expression were observed 55.6% (20/36) in ILCs compared with 4.1% (9/221) in IDCs (P < 0.001).

CONCLUSIONILC has several specific biological and prognostic characteristics which are different in IDC. Different expression patterns of E-cadherin and p120-catenin proteins can be helpful to recognize ILC from IDC.

Bone Neoplasms ; secondary ; Breast Neoplasms ; metabolism ; pathology ; Cadherins ; metabolism ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; secondary ; Carcinoma, Lobular ; metabolism ; pathology ; secondary ; Catenins ; metabolism ; Cytoplasm ; metabolism ; Diagnosis, Differential ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms ; secondary ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Retrospective Studies ; Survival Rate

OBJECTIVEThe aim of this study is to compare the clinicopathologic characteristics and disease-free survival of triple-negative breast cancer with human epidermal growth factor receptor-2-overexpressing (Her-2-overexpressing) breast cancer.

METHODS770 breast cancer patients were surgically treated between 1998 and 2003 in Changhai Hospital, Shanghai. Patients with triple negative phenotype were identified from those using immunochemistry and CISH. The differences between triple-negative breast cancer and Her-2-overexpressing breast cancers were analyzed in p53 and E-cadherin status, age, tumor size, tumor location, histological types and grading, lymph node metastasis, AJCC stage, chemotherapy and surgical procedures,as well as identified prognostic factors with regards to disease-free survival.

RESULTSNinety-six (12.5%) patients with triple-negative phenotype, and 164 (21.3%) with Her-2-overexpressing one were identified from the 770 breast cancer patients. No significant difference between two phenotypes in p53 and E-cadherin expression was found (P>0.05). When compared with Her-2-overexpressing breast cancer patients, triple negative breast cancer patients experienced more lymph node metastases (71.9% vs. 58.5%, P = 0.034), and had a higher percentage of more than 10 lymph nodes metastases (26.0% vs. 12.2%, P = 0.034); and showed a higher percentage of histological grade 3 (67.7% vs. 42.1%, P<0.0001). Furthermore, the tumor size was found to be related to lymph node metastasis in triple-negative breast cancer patients (P = 0.024). No significant difference between the two phenotypes in the rates of local recurrence and distant metastasis was observed (P>0.05). However, 5-year disease-free survival in patients with triple negative phenotype was significantly shorter than that in the patients with Her-2-overexpressing phenotype (61.85 mon vs. 78.69 mon, P = 0.047).

CONCLUSIONCompared with Her-2-overexpressing breast cancer, triple-negative breast cancer is more malignant and has a poorer disease-free survival.

Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms ; secondary ; Breast Neoplasms ; metabolism ; pathology ; Cadherins ; metabolism ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carcinoma, Lobular ; metabolism ; pathology ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Tumor Burden ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo analyze the relationship between Duffy antigen receptor for chemokines (DARC) and the metastasis potential in human breast cancer. METHODS Breast cancer tissue sections from 75 patients, grouped according to the local lymph node status were examined immunohistochemically for protein level of DARC. Microvessel density (MVD) was counted by endothelial cells immunostained using anti-CD34 antibody.

RESULTSStrong positive DARC immunostaining in lymph node negative and positive groups was detected in 31 cases (81.6%) and 18 cases (48.6%), respectively (P < 0.01). MVD was (35.67 +/- 17.96)/HP and (53.38 +/- 20.29)/HP in DARC strong positive and less positive cases (P < 0.01). In those patients with lung, bone, hepatic distant metastasis (13 cases), 9 cases (69.2%) were DARC less positive, 4 cases (30.8%) were DARC strong positive. The correlation coefficient was -0.412 between DARC expression and MVD and the corresponding value was -0.346 between DARC expression and lymph node status and -0.333 between DARC expression and distant metastasis in breast cancer.

CONCLUSIONDARC may play a negative role in the process of neoangiogenesis, and probably has an association with the lymph node status.

Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; analysis ; Bone Neoplasms ; metabolism ; secondary ; Breast Neoplasms ; blood supply ; metabolism ; pathology ; Down-Regulation ; Duffy Blood-Group System ; metabolism ; Female ; Humans ; Immunohistochemistry ; Liver Neoplasms ; metabolism ; secondary ; Lung Neoplasms ; metabolism ; secondary ; Lymphatic Metastasis ; Middle Aged ; Neovascularization, Pathologic ; metabolism ; pathology ; Receptors, Cell Surface ; metabolism ; Survival Analysis

OBJECTIVETo explore the expression of the epithelial cell adhesion molecule (EpCAM) in prostate cancer (PCa) and its clinical significance.

METHODSWe collected tissue samples from 63 cases of PCa, 46 cases of prostatic intraepithelial neoplasia (PIN), and 58 cases of benign prostatic hyperplasia (BPH) adjacent to PCa and determined the expression of EpCAM in the epithelial and stromal cells by immunohistochemistry.

RESULTSThe positive expression rates of EpCAM in the epithelial cells were significantly higher in PCa and PIN than in PCa-adjacent BPH (98. 4 and 97. 8 vs 51.7%, P <0. 01), and so was that in the stromal cells of PCa than in those of PCa-adjacent PIN (89.5 vs 50.0%, P <0.01). The expression of EpCAM.was remarkably higher in the stromal cells of bone metastasis than in those of non-bone metastasis tissue (100. 0 vs 40. 0%, P <0. 01) but showed no statistically significant differences between the highly and poorly differentiated PCa tissues (88.5 vs 91.9%, P >0.05).

CONCLUSIONThe expression level of EpCAM in the stromal cells of PCa is related to the occurrence, progression, and bone metastasis of the tumor, and therefore may be used as a marker in the early diagnosis of PCa as well as a predictor of bone metastasis of the tumor.

Antigens, Neoplasm ; metabolism ; Biomarkers ; metabolism ; Bone Neoplasms ; metabolism ; secondary ; Cell Adhesion Molecules ; metabolism ; Disease Progression ; Epithelial Cell Adhesion Molecule ; Epithelial Cells ; metabolism ; Humans ; Immunohistochemistry ; Male ; Prostatic Hyperplasia ; metabolism ; Prostatic Intraepithelial Neoplasia ; metabolism ; Prostatic Neoplasms ; metabolism ; Stromal Cells ; metabolism

Skeletal metastases result in significant morbidity and mortality. This is particularly true of cancers with a strong predilection for the bone, such as breast, prostate, and lung cancers. There is currently no reliable cure for skeletal metastasis, and palliative therapy options are limited. The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target. Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments. In this review, we discuss pathologic process of bone metastasis, the roles of the Wnt signaling, and the available experimental models and treatments.
Animals ; Bone Neoplasms ; drug therapy ; metabolism ; radiotherapy ; secondary ; surgery ; Breast Neoplasms ; metabolism ; pathology ; Disease Models, Animal ; Drug Delivery Systems ; Female ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Prostatic Neoplasms ; metabolism ; pathology ; Wnt Proteins ; metabolism ; Wnt Signaling Pathway ; beta Catenin ; metabolism

OBJECTIVETo analyze the clinicopathologic and immunohistochemical features and prognosis of papillary renal cell carcinoma (PRCC) in 19 cases.

METHODSA retrospective study was performed including reviewing the clinical documents and pathological sections of 19 cases of PRCC. Immunohistochemical staining were performed and follow-up was made in 16 cases.

RESULTSThere were 11 men and 8 women included in this study. The mean age was 52 years (range, 33 to 82 years old). Clinically, most tumors were found incidentally by physical examination because the majority of patients were asymptomatic. Histologically, the PRCC were characterized by varying proportions of papillary and tubular architecture covered by single- or multiple-layer of tumor cells with scanty or voluminous basophilic or eosinophilic cytoplasm. Foam cells and psammoma bodies were seen in some papillary cores and stroma, and the cytoplasm of some tumor cells contained hemosiderin. Of these 19 patients, 12 (63.2%) and 7 (36.8%) were diagnosed as type I and type II PRCC, respectively. The Fuhrman nuclear grade in all the type I PRCC was grade 1 - 2, significantly lower than that in the type II PRCC. Immunohistochemically, the PRCC often showed positive immunostaining for vimentin, EMA, CKpan, CK7, CD10 and p504s. Among the 19 patients, 16 were followed-up from 2 to 67 months. The distant metastasis, including lung, liver and bone metastases were detected in 3 patients at 3, 8, and 9 months after surgery, which were all of type II PRCC. Two patients died of other diseases. The other 11 patients were alive without recurrence or metastasis.

CONCLUSIONTwo subtypes of PRCC show different features of morphology, immunohistochemistry and prognosis. The type II PRCC tends to have unfavorable prognosis in comparison with type I PRCC. The presence of higher nuclear grade, sarcomatoid elements or clear cell carcinoma structure may indicate an aggressive behavior and poor prognosis.

Adult ; Aged ; Aged, 80 and over ; Bone Neoplasms ; secondary ; Carcinoma, Renal Cell ; classification ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Keratin-7 ; metabolism ; Kidney Neoplasms ; classification ; metabolism ; pathology ; surgery ; Liver Neoplasms ; secondary ; Lung Neoplasms ; secondary ; Male ; Middle Aged ; Mucin-1 ; metabolism ; Prognosis ; Racemases and Epimerases ; metabolism ; Retrospective Studies ; Vimentin ; metabolism

OBJECTIVETo observe the effect of Tiam-l gene silencing on the metastasis of human colorectal carcinoma cell line SW480 in nude mice by real-time whole-body fluorescence imaging.

METHODSEnhanced green fluorescence protein (EGFP)-labeled human colorectal carcinoma cells, SW480/EGFP(+)/Tiam-1(-) and SW480/EGFP(+), were implanted into nude mice via tail vein injection or orthotopic colonal inoculation, and real-time whole-body fluorescence imaging was performed to compare the difference in tumor progression and metastasis between the two cells.

RESULTSBoth SW480/EGFP(+) and SW480/ EGFP(+)/Tiam-1(-) cells stably expressed EGFP, and Tiam1 gene expression was reduced in SW480/EGFP(+)Tiam-1(-) to 30% of the expression level in SW480/EGFP(+) cells. The growth rate of the two cell lines had no significant difference in vitro (P>0.05), but SW480/EGFP(+)/Tiam1(-) cell proliferation and metastasis were depressed obviously in comparison with SW480/EGFP(+) in vivo (P<0.05).

CONCLUSIONTiam-1 gene may play an important role in invasion and metastasis of human colorectal cancer.

Animals ; Blotting, Western ; Bone Neoplasms ; genetics ; metabolism ; secondary ; Cell Line, Tumor ; Cell Survival ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; Diagnostic Imaging ; methods ; Female ; Fluorescence ; Gene Silencing ; Green Fluorescent Proteins ; chemistry ; genetics ; metabolism ; Guanine Nucleotide Exchange Factors ; genetics ; metabolism ; Immunohistochemistry ; Liver Neoplasms ; genetics ; metabolism ; secondary ; Lung Neoplasms ; genetics ; metabolism ; secondary ; Mice ; Mice, Nude ; Microscopy, Fluorescence ; Neoplasm Transplantation ; T-Lymphoma Invasion and Metastasis-inducing Protein 1 ; Transplantation, Heterologous

OBJECTIVETo investigate the correlation between a diverse of clinical factors and bone metastases of prostate cancer.

METHODSThe clinical data of 80 patients with prostate cancer were collected and analyzed. The correlations of age, alkaline phosphotase (ALP), prostate specific antigen (PSA), erythrocyte sedimentation rate (ESR), Gleason score, and expressions of androgen receptor (AR) and Ki-67 with bone metastases were analyzed by one-way ANOVA and Logistic regression analysis. The cutoff value, sensitivity and specificity of the independent correlation factors were calculated.

RESULTSForty-five of the 80 patients (56%) were found to have bone metastasis, who had significantly older age and higher levels of ALP, PSA, ESR, Gleason score, and expressions of AR and Ki-67 than those without bone metastasis (P<0.05). Logistic regression analysis identified PSA, Gleason score and AR expression as independent factors correlated with bone metastasis with OR (95% CI) of 1.005 (1.001, 1.009) (P=0.008), 5.356 (1.431, 20.039) (P=0.013), and 18.594 (2.460, 140.524) (P=0.005), respectively. The cutoff values of PSA, Gleason Score and AR were 67.1 ng/ml, 7.5, and 2.5, respectively; their sensitivities were 55.6%, 75.6%, and 84.0% for predicting bone metastasis with specificities of 97.1%, 82.9%, and 91.4%, respectively.

CONCLUSIONOf the factors analyzed, PSA, Gleason score and AR expression, but not age, ALP, PSA, ESR, or Ki-67 expression, are the predictive factors of bone metastasis of prostate cancer.

Alkaline Phosphatase ; metabolism ; Bone Neoplasms ; diagnosis ; secondary ; Humans ; Male ; Neoplasm Grading ; Predictive Value of Tests ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; pathology ; Receptors, Androgen ; metabolism ; Sensitivity and Specificity