LAPTM4B Predicts Axillary Lymph Node Metastasis in Breast Cancer and Promotes Breast Cancer Cell Aggressiveness in Vitro.

PURPOSE: Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is associated with the prognosis of several human malignancies. In this study, the role of LAPTM4B in the metastatic potential of breast cancer (BC) and its underlying molecular mechanisms were investigated. METHODS: The relationship between LAPTM4B expression and axillary lymph node metastasis was determined in 291 BC specimens by immunohistochemistry. The expression of LAPTM4B in paired BC cells was overexpressed and inhibited to analyse the role of LAPTM4B in the aggressiveness of BC. Cell proliferation, migration and invasion were assessed in vitro. Metastasis-related protein levels were detected through Western blot. RESULTS: Immunohistochemical staining demonstrated that high expression level of LAPTM4B was independently associated with axillary lymph node metastasis (odds ratio=2.428; 95%CI=1.333- 4.425; P=0.004). The LAPTM4B inhibition in MCF-7 cells inhibited cell proliferation, migration, invasion, and resulted in simultaneous downregulation of phosphorylated N-cadherin, vimentin, and upregulation of E-cadherin. By contrast, the LAPTM4B overexpression promoted cell proliferation, migration, invasion, and led to simultaneous upregulation of N-cadherin, vimentin, and downregulation of E-cadherin in T47D cells. CONCLUSIONS: High expression level of LAPTM4B predicts tumor metastatic potential in patients with BC. Our results provide the first evidence of the role of LAPTM4B as an Epithelial-mesenchymal transition (EMT) inducer that promotes aggressiveness in BC cells.

Overexpression of TNFAIP8 is associated with tumor aggressiveness and poor prognosis in patients with invasive ductal breast carcinoma.

Tumor necrosis factor α-induced protein 8 (TNFAIP8), a transcription factor nuclear factor κB-inducible, antiapoptotic and oncogenic molecule, is associated with prognosis of several human malignancies. However, the relationship between TNFAIP8 and the prognosis of the invasive ductal carcinoma (IDC) of the breast remains unclear. TNFAIP8 expression was evaluated using real-time polymerase chain reaction (PCR) and Western blot analysis in 20 fresh IDC tissues and immunohistochemical analysis in 351 paraffin-embedded IDC tissues. Real-time PCR and Western blot analysis demonstrated that both TNFAIP8 messenger RNA and protein were up-regulated in IDC tissues compared with the paired adjacent noncancerous tissues. Immunohistochemistry revealed that TNFAIP8 expression was significantly correlated with some clinicopathological factors, including axillary lymph node metastasis (P=.001), advanced TNM stage (P<.001), high histologic grade (P<.001), molecular subtype (P<.001), and postoperative recurrence (P<.001). Univariate and multivariate logistic regression analyses demonstrated that TNFAIP8 overexpression was strongly associated with axillary lymph node metastasis (odds ratio, 1.818; 95% confidence interval, 1.167-2.832; P=.008). Moreover, Kaplan-Meier analysis indicated that IDC patients with high TNFAIP8 expression had a shorter survival time than did those with low TNFAIP8 expression, and multivariate analysis indicated that TNFAIP8 was an independent prognostic factor for overall survival and disease-free survival in IDC (P=.041 and P=.020, respectively). Therefore, TNFAIP8 overexpression may contribute to tumor progression, and it may be a novel prognostic biomarker for the patients with IDC.

Overexpression of eukaryotic initiation factor 5A2 (EIF5A2) is associated with cancer progression and poor prognosis in patients with early-stage cervical cancer.

AIMS: As one of the only two isoforms of the eukaryotic initiation factor (EIF)5A family, EIF5A2 plays an important role in tumour progression and prognosis evaluation. The aim of this study was to investigate EIF5A2 expression in International Federation of Gynecology and Obstetrics (FIGO) stage I-II cervical cancer and to evaluate its clinical significance. METHODS AND RESULTS: The mRNA and protein expression levels of EIF5A2 were analysed in 20 tissue samples of FIGO stage I-II cervical cancer and paired surrounding non-tumour cervical tissues by real-time polymerase chain reaction and western blot analysis. Immunohistochemistry was performed to examine EIF5A2 protein expression in paraffin-embedded tissues from 314 patients with cervical cancer. The mRNA and protein expression levels of EIF5A2 were significantly elevated in tumour tissues. The increased EIF5A2 expression was correlated with higher FIGO stage (P < 0.001), deep cervical stromal invasion (P = 0.026), lymphovascular space involvement (P = 0.002), pelvic lymph node metastasis (P < 0.001) and postoperative recurrence (P < 0.001) in patients with cervical cancer. Patients with tumours showing high EIF5A2 expression had a poorer survival time than those with normal EIF5A2 expression, especially the patients with negative pelvic lymph nodes and FIGO stage II. In addition, multivariate Cox analysis showed that high EIF5A2 expression was an independent prognostic factor for overall survival [hazard ratio 1.949; 95% confidence interval (CI) 1.116-3.404; P = 0.019] and disease-free survival (hazard ratio 1.980; 95% CI 1.189-3.297; P = 0.009). CONCLUSIONS: EIF5A2 overexpression may contribute to cancer progression and poor prognosis. Therefore, EIF5A2 could be a novel potential prognostic marker for FIGO stage I-II cervical cancer.

DLL4 as a predictor of pelvic lymph node metastasis and a novel prognostic biomarker in patients with early-stage cervical cancer.

Delta-like ligand 4 (DLL4), one of the five Notch signaling ligands in mammals, has an important function in proliferation, invasion, metastasis, progression, and angiogenesis of malignancies. This study aimed to investigate DLL4 expression level in early-stage cervical carcinoma and to evaluate its clinical significance. We used fresh frozen and paraffin-embedded cervical cancer tissues to analyze DLL4 expression and its clinical significance. DLL4 expression at both mRNA and protein levels in cervical cancer tissues was significantly higher than that in normal cervical tissues. High DLL4 protein level was clearly correlated with high International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.044), lymphovascular space involvement (LVSI) (P = 0.015), pelvic lymph node metastasis (PLNM) (P = 0.001), and recurrence (P < 0.001). Univariate and multivariate logistic regression analyses demonstrated that DLL4 overexpression was strongly associated with lymph node metastasis (odds ratio, 2.790; 95 % CI, 1.344-5.791; P = 0.006). Moreover, survival analysis revealed that DLL4 expression was an independent factor of unfavorable overall survival (hazard ratio, 2.130; 95 % CI, 1.108-4.097; P = 0.023) and disease-free survival (hazard ratio, 1.965; 95 % CI, 1.085-3.560; P = 0.026) in patients with cervical cancer. Overall, our data indicate that high DLL4 expression predicts pelvic lymph node metastasis and poor survival in cervical cancer. Therefore, DLL4 may be a potential clinical diagnostic marker for patients with early-stage cervical cancer.

Aberrant expression of δ-like ligand 4 contributes significantly to axillary lymph node metastasis and predicts postoperative outcome in breast cancer.

δ-Like ligand 4 (DLL4), a ligand for the Notch family of receptors, forecasts the prognosis of several human malignancies. However, the expression and role of DLL4 in breast cancer remain largely unknown. In the present study, we first evaluated whether the overexpression of DLL4 could be used as an indicator of axillary lymph node metastasis and postoperative prognosis in breast cancer. The amount of DLL4 protein was assessed in 204 tumor specimens by immunohistochemical staining. Overexpression was detected in 142 (69.6%) and significantly associated with advanced TNM stage (III versus I, P = .031; III versus II, P = .038), axillary lymph node metastasis (P = .001), and postoperative recurrence (P = .007). Moreover, using univariate and multivariate logistic regression analysis, we found that DLL4 overexpression was strongly associated with axillary lymph node metastasis (odds ratio, 3.036; 95% confidence interval [CI], 1.561, 5.902; P = .001). Lastly, survival analysis showed that patients with low DLL4 expression had a significantly better overall survival and disease-free survival than patients with high DLL4 expression. Furthermore, in multivariate analysis, DLL4 overexpression was an independent risk factor for unfavorable overall survival (hazard ratio, 2.662; 95% CI, 1.300, 5.452; P = .007) and disease-free survival (hazard ratio, 2.568; 95% CI, 1.353, 4.876; P = .004). Taken together, these results suggest that high expression of DLL4 is associated with axillary lymph node metastasis and a poor prognosis in breast cancer, suggesting its value as a diagnostic marker for breast cancer.

A metabolomics approach for predicting the response to neoadjuvant chemotherapy in cervical cancer patients.

Cervical cancer is a clinical and pathological heterogeneity disease, which requires different types of treatments and leads to a variety of outcomes. In clinical practice, only some patients benefit from chemotherapy treatment. Identifying patients who will be responsive to chemotherapy could increase their survival time, which has important implications in personalized treatment and outcomes, while identifying non-responders may reduce the likelihood for these patients to receive ineffective treatment and thereby enable them to receive other potentially effective treatments. Plasma metabolite profiling was performed in this study to identify the potential biomarkers that could predict the response to neoadjuvant chemotherapy (NACT) for cervical cancer patients. The metabolic profiles of plasma from 38 cervical cancer patients with a complete, partial and non-response to NACT were studied using a combination of liquid chromatography coupled with mass spectrometry (LC/MS) and multivariate analysis methods. L-Valine and L-tryptophan were finally identified and verified as the potential biomarkers. A prediction model constructed with L-valine and L-tryptophan correctly identified approximately 80% of patients who were non-response to chemotherapy and 87% of patients who were had a pathologically complete response to chemotherapy. The model has an excellent discriminant performance with an AUC of 0.9407. These results show promise for larger studies that could produce more personalized treatment protocols for cervical cancer patients.

Low ING4 protein expression detected by paraffin-section immunohistochemistry is associated with poor prognosis in untreated patients with gastrointestinal stromal tumors.

BACKGROUND: Inhibitor of growth 4 (ING4) has deserved attention as a tumor suppressor gene in many malignant tumors. In our study, we investigated ING4 immunoexpression in gastrointestinal stromal tumors (GISTs) and its prognostic value. METHOD: The expression of ING4 and Ki67 was investigated in 41 samples of various risk gastrointestinal stromal tumors by immunohistochemical technique. The associations of ING4 expression and clinicopathological parameters, and prognosis of the patients, were analyzed by multivariate Cox regression analysis. RESULTS: ING4 expression showed a decreased trend from lower-risk to high-risk gastrointestinal stromal tumors, and an opposite trend for Ki67 expression. In lower-risk tumors, it was found the expression level of ING4 was 78.95 % ± 27.90 % and that of Ki67 was 4.42 % ± 3.75 %. However, in high-risk tumors, the expression level of ING4 was 9.23 % ± 7.66 % and that of Ki67 was 18.50 % ± 9.09 %. There was a strongly negative correlation between the expression levels of ING4 and Ki67. A significant difference was observed in the expression of ING4 between invasion and non-invasion (p < 0.001). The expression of ING4 was markedly correlated with tumor size (p < 0.001), mitotic index (p < 0.001), tumor necrosis (p = 0.021), invasion (p < 0.001), recurrence and metastasis (p = 0.021), and mortality (p < 0.001). CONCLUSION: The low expression level of ING4 protein was correlated with high-risk GISTs. ING4 might be involved in the progression of GISTs and inhibit its invasion. ING4 might be one of the prognostic indicators in GISTs.

Overexpression of multiple myeloma SET domain (MMSET) is associated with advanced tumor aggressiveness and poor prognosis in serous ovarian carcinoma.

Multiple myeloma SET domain (MMSET) has been shown to be overexpressed in many different cancer tissues. Our study was to investigate the expression of MMSET in serous ovarian carcinoma and to evaluate its clinical significance in patients with serous ovarian carcinoma. Immunohistochemistry was performed to determine the expression of MMSET in 132 serous ovarian carcinoma, 32 normal ovarian and fallopian tube specimens. The high expression of MMSET was observed in 49.2% (65/132) in patients with serous ovarian carcinoma. MMSET high expression correlated with the advanced extent of serous ovarian carcinoma and poor outcome. MMSET may serve as a new molecular marker to predict the prognosis of serous ovarian carcinoma in the clinic.

Evaluation of chemotherapy response with serum squamous cell carcinoma antigen level in cervical cancer patients: a prospective cohort study.

MRI does not always reflect tumor response after chemotherapy. Therefore, it is necessary to explore additional parameters to more accurately evaluate tumor response for the subsequent clinical determination about radiotherapy or radical surgery. A training cohort and an external validation cohort were used to examine the predictive performance of SCC-ag to evaluate tumor response from teaching hospital of Harbin Medical University. The study included 397 women with SCC (age: 28-73 years). Patients consecutively enrolled between August 2008 and January 2010 (n = 205) were used as training cohort. Patients consecutively enrolled between February 2010 and May 2011 (n = 192) were used as validation cohort. A multivariate regression analysis of the data from the training cohort indicated that serum SCC-ag level is an independent factor for neo-adjuvant chemotherapy (NACT) response. Analysis of the data from the validation cohort suggested that chemotherapy response could be more accurately predicted by SCC-ag than by magnetic resonance imaging (MRI) (sensitivity (Se): 0.944 vs. 0.794; specificity (Sp): 0.727 vs. 0.636; positive predictive value (PPV): 0.869 vs. 0.806; negative predictive value (NPV): 0.873 vs. 0.618; the area under ROC curve (AUC): 0.898 vs. 0.734). Combining SCC-ag with MRI was more powerful than MRI alone (Se: 0.952 vs. 0.794; Sp: 0.833 vs. 0.636; PPV: 0.916 vs. 0.806; NPV: 0.902 vs. 0.618; AUC: 0.950 vs. 0.734). Our study indicates that serum SCC-ag level is a sensitive and reliable measure to evaluate cervical cancer response to chemotherapy. Using SCC-ag in combination with MRI findings further improves the predictive power.

Overexpression of MMSET in endometrial cancer: a clinicopathologic study.

BACKGROUND AND OBJECTIVES: Endometrial cancer is a common gynecologic malignancy. It has been reported that overexpression of multiple myeloma SET (MMSET) promoted cellular adhesion, clonogenic growth, and tumorigenicity in other carcinomas. Therefore, the authors expected to investigate whether MMSET overexpression is an independent prognostic marker in endometrial cancer. METHODS: Immunohistochemistry was performed to examine the expression of MMSET in 161 endometrial cancer specimens and 62 normal endometrium specimens. The correlation of MMSET expression with clinicopathological parameters was assessed using χ(2) analysis. Patients' survival was analyzed using the Kaplan-Meier and log-rank tests. Cox regression was used for the multivariate analysis of prognostic factors. RESULTS: MMSET immunoreactivity was overexpressed in endometrial cancer compared with normal endometrium (P < 0.001). Moreover, MMSET expression was correlated with FIGO stage, histological grade, depth of myometrial invasion, lymph node metastasis, and vascular/lymphatic invasion. Furthermore, Patients with positive MMSET expression had significantly poorer overall survival and disease-free survival compared with patients with negative expression of MMSET (both P < 0.001, log-rank test). Multivariate Cox regression analysis revealed that positive MMSET expression was an independent prognostic factor for both OS and DFS of patients with endometrial cancer (P = 0.008 and P = 0.048, respectively). CONCLUSIONS: Overexpression of MMSET may contribute to the progression of endometrial cancer and also may serve as a new biomarker to predict the prognosis of endometrial cancer.

Elevated expression of MAC30 predicts lymph node metastasis and unfavorable prognosis in patients with epithelial ovarian cancer.

Meningioma-associated protein (MAC30), first described to be overexpressed in meningiomas, exhibits altered expression in certain human tumors. The definite role of MAC30 is not clear now, and few studies have documented the value of MAC30 in epithelial ovarian cancer (EOC). The aim of this study was to investigate the expression of MAC30 in EOC and to evaluate its clinical significance in patients with EOC. A total of 266 patients with EOC who undergone complete cytoreductive surgery from November 2003 to September 2006 were eligible for this study. The expression of MAC30 in epithelial ovarian tumor tissues was examined immunohistochemically. High expression of MAC30 was observed in 66.17 % of EOC. The high MAC30 expression group had more advanced stages, poorer histological grade, lymph node metastasis, and recurrence than those with low MAC30 expression. Moreover, the presence of lymph node metastasis was significantly associated with MAC30 expression (OR 2.888, 95 % CI 1.428-5.838, P = 0.003). In addition, it was also shown that high MAC30 expression significantly correlated with poorer overall survival and progression-free survival (both P < 0.001). Multivariate Cox regression analysis revealed that MAC30 expression status was an independent prognostic factor for both overall survival and progression-free survival (P = 0.001 and P = 0.002, respectively) of patients with EOC. Our study provides evidence that patients with expression of MAC30 in EOC have high malignant potential, and MAC30 may serve as a new molecular marker to predict the lymph node metastasis and prognosis of patients with EOC in the clinic.

Elevated expression of astrocyte elevated gene-1 (AEG-1) is correlated with cisplatin-based chemoresistance and shortened outcome in patients with stages III-IV serous ovarian carcinoma.

AIMS: To correlate astrocyte elevated gene-1 (AEG-1) expression with the clinicopathological features and outcome of patients with stages III-IV ovarian serous carcinoma, and to clinically assess the involvement of AEG-1 in acquired cisplatin resistance. METHODS AND RESULTS: The frequency and intensity of immunohistochemical AEG-1 expression increased in a step-wise fashion from normal to chemosensitive to chemoresistant tissues. These observations were confirmed by Western blot analysis. AEG-1 expression level was correlated with lymph nodal metastasis, histological differentiation, residual tumour size and response to primary chemotherapy. Five-year progression-free survival (PFS) and overall survival (OS) rates were lower in the high-expression group than that in the low-expression group. AEG-1 overexpression was an independent but poor prognostic factor in the OS and PFS of these patients, as determined by multivariate Cox regression analysis. Multivariate logistic regression analysis revealed that the presence of cisplatin-based chemoresistance was significantly associated with expression level of AEG-1 and the degree of residual disease (P = 0.0001 and P = 0.0027, respectively). CONCLUSION: Our findings indicate that tumour AEG-1 overexpression is associated with poor prognosis and cisplatin resistance in advanced serous ovarian cancer.

LAPTM4B overexpression is a novel independent prognostic marker for metastatic ovarian tumors.

OBJECTIVE: Metastatic ovarian tumors are a series of lethal carcinomas that almost always have bad prognosis. Their prognoses, however, vary depending on the primary tumor malignancies of each. It has been reported that LAPTM4B, a novel tumor-associated gene, might indicate a worse prognosis when it was overexpressed in other carcinomas. Therefore, the authors expected to investigate whether LAPTM4B overexpression is an independent prognostic marker in metastatic ovarian tumors. METHODS: Immunohistochemistry was used to assess LAPTM4B expression in metastatic ovarian tumors from 102 patients. Subsequently, univariate and multivariate survival analyses with Cox regression were performed to determine the association between LAPTM4B expression and prognosis. To identify any differences in prognosis between the 2 groups of patients with differing primary malignancies, the log-rank test was used. RESULTS: The median overall and progression-free survival rates of patients with tumors of gastrointestinal tract origin were 0.97 and 0.51 years, respectively, and both were statistically significantly lower than those of patients with tumors of breast origin (P < 0.0001), which were 2.68 and 1.96 years, accordingly. Of 102 patients, 77 were classified as having a high expression of LAPTM4B, and LAPTM4B expression had a significant association with the prognosis of metastatic ovarian tumors (P < 0.01); no statistically significant interaction between LAPTM4B expression and primary malignancies was detected (P > 0.1). On the other hand, medians of overall survival and progression-free survival of patients with tumors of gastrointestinal tract origin were significantly lower than those of patients with tumors of breast origin (P < 0.0001). CONCLUSIONS: Patients with metastatic ovarian tumors of breast origin had significantly better prognosis than those with the disease from gastrointestinal tract primary malignancies. LAPTM4B overexpression might be an independent prognostic marker of metastatic ovarian tumors.

AEG -1 overexpression: a novel indicator for peritoneal dissemination and lymph node metastasis in epithelial ovarian cancers.

OBJECTIVE: Despite advances in chemotherapy and cytoreductive surgery, ovarian cancer remains the most lethal gynecological malignancy with a 5-year survival rate of 25% to 30% in advanced stage disease. Our purpose is to evaluate whether astrocyte elevated gene-1 (AEG-1) is a novel predictor of peritoneal dissemination and lymph node metastasis in epithelial ovarian cancer (EOC), which was not previously studied by others. MATERIALS AND METHODS: Through immunohistochemical and Western blot analysis, AEG-1 expression was evaluated in 25 normal ovarian and 157 EOC specimens. The relationship between AEG-1 expression and EOC metastasis was determined by univariate and multivariate analyses. RESULTS: Western blotting analysis revealed that AEG-1 was overexpressed in metastatic tissues from patients with ovarian cancers. Immunohistochemistry results showed that 83 (95.4%) presented peritoneal dissemination; 41 (47.1%) had lymph node metastasis among 87 patients with AEG-1 overexpression. Univariate and multivariate logistic regression analyses demonstrated that AEG-1 overexpression correlated with peritoneal dissemination and lymph node metastasis in EOC. We further found that the positive and specificity predictive value of AEG-1 staining were better for peritoneal metastasis, whereas the negative and sensitivity predictive value of AEG-1 staining were better for lymph node metastasis. The odds ratio of high-to-low expression for peritoneal dissemination was 8.541 (95% confidence interval, 2.561-37.461), and that for lymph node metastasis was 9.581 (95% confidence interval, 2.613-23.214). CONCLUSIONS: The present findings indicate that AEG-1 is overexpressed in a great portion of EOC patients with peritoneal dissemination and/or lymph node metastasis and may be clinically useful for predicting metastasis in EOC. Our findings might provide some benefits for metastatic EOC patients in the clinic.

Comparison of PET-CT images with the histopathological picture of a resectable primary tumor for delineating GTV in nonsmall cell lung cancer.

OBJECTIVE: This study was designed to investigate the feasibility of a method derived from fused positron emission tomography-computed tomography (PET-CT) images for the delineation of gross tumor volume (GTV) in nonsmall cell lung cancer (NSCLC) and to explore the correlation between PET-CT and histopathological findings. METHODS: Thirty-seven patients were enrolled in this study; all patients were evaluated by PET-CT and underwent surgery within 1 week after the scan. The radiation oncologist, together with the radiologist, first delineated the GTV-based CT and then with an experienced nuclear medicine physician contoured the same GTV using the distinctive visual 'halo' in fused PET-CT images. The characteristics of the halo phenomenon were analyzed, including the standardized uptake value (SUV). The excised surgical specimens were labeled and the maximum diameter of the tumor in the right-left axis of the tissue blocks was measured on consecutive histopathology slides; the histopathological slice images were scanned using a digital pathology scanner after staining with hematoxylin and eosin. RESULTS: The mean SUV of the external margins of the halos was 2.41±0.73 (range 1.4-4.1); the histopathological type and T-stage significantly influenced the SUV of the external margin of the halos (P=0.004 and 0.027). The correlation coefficients of maximum diameter in the right-left axis and in the anterior-posterior axis between fused PET-CT images and histopathology were 0.935 and 0.943, respectively; the values between CT imaging and histopathological examination were 0.82 and 0.763. CONCLUSION: There is a correlation between GTV based on the'halo' of fused PET-CT images and the excised surgical specimen of primary tumor.It may be feasible to use the 'halo' characteristics in fused PET-CT images to delineate GTV in NSCLCs, but its reliability should be further investigated to establish an accurate spatial imaging-pathology correlation for primary tumors delineation in NSCLCs.

Comparison between vascular cast and three-dimensional ultrasonography on tumor vessels.

AIM: The aim of this study was to characterize the morphology of renal tumor vessels. METHODS: Twenty-two patients with kidney neoplasm underwent three-dimensional reconstruction prior to surgery. The vascular cast of kidney specimens was obtained after surgery. RESULTS: The vascular cast revealed proliferation, thickening, compression, displacement, and arteriovenous fistulae in tumor vessels, which were consistent with the findings from 3-D ultrasound (chi(2)=12.60, P<.01). CONCLUSION: Most renal cellular carcinomas are rich blood-supplied tumors with distinctive vasculature in the tumor region.

Interaction of p14ARF with Brca1 in cancer cell lines and primary breast cancer.

We report an association between p14ARF and Brca1 in which both proteins co-immunoprecipitate (co-IP) in DU145 cells. The N-terminal 64 residues of p14ARF encoded by exon 1beta are sufficient for this association. Inside the cell, ectopic p14ARF co-localizes with ectopic and endogenous Brca1 in A375 cells. Endogenous p14ARF co-localizes with endogenous Brca1 in DU145 cells but not in H1299 cells. Since p14ARF interacts with B23 in the nucleolus, Brca1 co-localizes with B23 in DU145 but not in H1299 cells. While ectopic ARF potently inhibited DU145 cell proliferation, it had no effect on the proliferation of H1299 cells, suggesting that the interaction between ARF and Brca1 contributes to ARF-mediated tumor suppression. Consistent with this notion, ectopic p14ARF modulates endogenous Brca1 expression in MCF7 breast cancer cells and p14ARF co-localizes with Brca1 in normal breast epithelial cells. This co-localization is enhanced in primary breast cancer. Taken together, the results show that p14ARF associates with Brca1, which may play a major role in tumor suppression.

Expression and correlation of CD44v6, vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9 in Krukenberg tumor.

AIM: To explore the expression and correlation of CD44v6, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and matrix metalloproteinase (MMP)-9 in Krukenberg and primary epithelial ovarian carcinoma. METHODS: The expressions of CD44v6, VEGF, MMP-2 and MMP-9 were detected by immunohistochemical method in 20 cases of normal ovarian tissues, 38 cases of Krukenberg tumor and 45 cases of primary epithelial ovarian carcinoma. RESULTS: The expression of CD44v6 (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: chi(2) = 4.516, P = 0.034; Krukenberg tumor tissue vs normal ovarian tissue: chi(2) = 19.537, P = 0.001) and VEGF (primary epithelial ovarian carcinoma tissue vs normal ovarian tissue: P = 0.026; Krukenberg tumor tissue vs normal ovarian tissue: chi(2) = 22.895, P = 0.001) was significantly higher in primary epithelial ovarian carcinoma tissue and Krukenberg tumor tissue than in normal ovarian tissue. The positive expression rate of MMP-2 and MMP-9 was 0% in the normal ovarian tissue. The positive expression rate of CD44v6 (chi(2) = 10.398, P = 0.001), VEGF (chi(2) = 13.149, P = 0.001), MMP-2 (chi(2) = 33.668, P = 0.001) and MMP-9 (chi(2) = 38.839, P = 0.001) was remarkably higher in Krukenberg tumor than in primary epithelial ovarian carcinoma. The correlation of CD44v6, VEGF, MMP-2, and MMP-9 was observed in primary epithelial ovarian carcinoma and Krukenberg tumor. CONCLUSION: CD44v6, VEGF, MMP-2, and MMP-9 are involved in ovarian carcinoma, gastric cancer and Krukenberg tumor. Detection of CD44v6, VEGF, MMP-2 and MMP-9 may contribute to the diagnosis of ovarian carcinoma, gastric cancer, and Krukenberg tumor.