Collision metastasis of breast and thyroid carcinoma to a single cervical lymph node: report of a case.

We herein report a rare case of collision lymph node metastases of breast and thyroid carcinomas. A 49-year-old female had undergone an extensively radical mastectomy of the right breast for inflammatory breast cancer at our hospital. Eleven months later, she presented with enlarged lymph nodes in her right lateral neck and multiple nodules in bilateral thyroid lobes. The patient underwent total thyroidectomy and radical dissection of the bilateral cervical lymph nodes. A histological examination showed multiple foci of papillary thyroid carcinoma (PTC) in the bilateral lobes. Surprisingly, concurrent metastases of breast carcinoma and PTC were shown in one of the lymph nodes from the right jugular region. This rare case of collision metastasis and the related literature are discussed.

Ubc9 expression predicts chemoresistance in breast cancer.

Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays an important role in tumorigenesis. Whether Ubc9 is involved in the chemoresistance of breast cancer remains unknown. In this study, we aimed to evaluate the contribution of Ubc9 in the chemoresistance of breast cancer. Immunohistochemistry (IHC) was used to examine the expression level of Ubc9. Chi-square test, Wilcoxon test, and one-way ANOVA were applied to analyze the relationship between Ubc9 expression, clinicopathologic features, and clinical response to neoadjuvant chemotherapy. The significance of variables for survival was analyzed by the Cox proportional hazards model in a multivariate analysis. Kaplan-Meier survival curves were plotted and log-rank test was performed. The proportion of Ubc9-positive cells was higher in invasive ductal carcinoma than in normal breast tissues [(48.48 ± 17.94)% vs. (5.82 ± 2.80)%, P < 0.001]. High Ubc9 expression was associated with poor differentiation (Χ² = 6.538, P = 0.038), larger tumor size (Χ² = 4.701, P = 0.030), advanced clinical stage (Χ² = 4.651, P = 0.031), lymph node metastasis (Χ² = 9.913, P = 0.010), basal-like phenotype (Χ² = 8.660, P = 0.034), and poor clinical response to neoadjuvant chemotherapy (Χ² = 11.09, P = 0.001). The expected 6-year cumulative disease-free survival rate was 87.32% in patients with low Ubc9 expression compared to 68.78% in those with high Ubc9 expression (Χ² = 4.289, P = 0.038). These data indicate that high Ubc9 expression correlates with poor response to chemotherapy and poor clinical prognosis.

Clinicopathological significance of expression of paxillin, syndecan-1 and EMMPRIN in hepatocellular carcinoma.

AIM: To evaluate the relationship of expression of paxillin, syndecan-1 and EMMPRIN proteins with clinicopathological features in hepatocellular carcinoma (HCC). METHODS: Fifty-one patients who underwent HCC resection were recruited in the study. Paxillin, syndecan-1 and EMMPRIN proteins in HCC tissues were detected with immunohistochemical staining. RESULTS: Of 51 cases of HCC, 23 (45%) exhibited paxillin protein positive expression. Of 42 cases of adjacent non-tumor liver tissues, 24 (57%) exhibited positive expression. Positive paxillin protein expression was associated with low differentiation (r = 0.406, P = 0.004), with the presence of portal vein thrombosis (r = 0.325, P = 0.021), with extra-hepatic metastasis (r = 0.346, P = 0.014). Of 51 cases of HCC, 28 (55%) exhibited syndecan-1 protein positive expression. Of 42 cases of adjacent non-tumor liver tissues, 23 (55%) exhibited positive expression. Positive snydecan-1 protein expression was associated with well differentiation (r = 0.491, P = 0.001), with no extra-hepatic metastasis (r = 0.346, P = 0.014). Of 51 cases of HCC, 28 (55%) exhibited EMMPRIN protein positive expression. Of 42 cases of adjacent non-tumor liver tissues, 21 (50%) exhibited positive expression. Expression of EMMPRIN protein was not associated with serum AFP level, HBsAg status, presence of microsatellite nodule, tumor size, presence of cirrhosis and necrosis, differentiation, presence of portal vein thrombosis, extra-hepatic metastasis, disease-free survival and overall survival (P>0.05). Expression of paxillin protein was correlated conversely with the expression of syndecan-1 protein in HCC (r = -0.366, P = 0.010). CONCLUSION: Expression of paxillin and syndecan-1 proteins in HCC may affect its invasive and metastatic ability of the tumor. There may be a converse correlation between the expression of paxillin and syndecan-1 protein in HCC. Expression of EMMPRIN protein may be detected in HCC, but it may play little role in the invasion and metastasis of HCC.

[Expression of vascular endothelial growth factor C and cyclooxygenase-2 in non-small-cell lung carcinoma and their clinical significance].

OBJECTIVE: To investigate the expression of vascular endothelial growth factor-C (VEGF-C) and cyclooxygenase-2 (COX-2) proteins, and their relationship with biological behaviors of non-small-cell lung carcinoma (NSCLC). METHODS: Immunohistochemical staining was used to detect the expression of VEGF-C and COX-2 proteins in 77 cases of NSCLC. The relationship was analyzed between the expression of VEGF-C, COX-2 and lymphatic vessel density (LVD), tumor size, histological type, differentiation, lymph node metastasis, clinical recurrence and survival time of the patients. RESULTS: Out of 77 cases of NSCLC, 45 cases and 29 cases showed positive expression of VEGF-C and COX-2 proteins, respectively. The expression rates of VEGF-C and COX-2 protein were 58.4% and 37.7%, respectively. The expression of VEGF-C protein was correlated negatively with the degree of differentiation of NSCLC (P < 0.05). The expression of VEGF-C was positively correlated with lymph node metastasis, LVD and tumor size (P < 0.01). The survival time of the patients was negatively correlated with the expression of VEGF-C (P < 0.01). The expression of COX-2 was positively correlated with LVD (P < 0.01). The survival time of the patients was negatively correlated with the expression of COX-2 (P < 0.05). CONCLUSION: The expression of VEGF-C and COX-2 proteins are closely correlated with the biological behaviors of NSCLC, especially VEGF-C protein. Its high expression suggests probable lymph node metastasis and poor prognosis.

CCL18 from tumor-associated macrophages promotes angiogenesis in breast cancer.

The infiltration of tumor-associated macrophages (TAMs) is associated with extensive angiogenesis, which contributes to a poor prognosis in breast cancer. However, anti-angiogenic therapy with VEGF-specific monotherapy has been unsuccessful in treating breast cancer, and the molecular mechanisms associated with chemoresistance remain unclear. Here, we investigated whether CCL18, a chemokine produced by TAMs, can stimulate angiogenesis in breast cancer, as well as the underlying mechanisms. Double immunohistochemical staining for CCL18 and CD34/CD31/vWF was performed in 80 breast cancer samples to study the correlation between CCL18+ TAMs and microvascular density (MVD). Cocultures of TAMs with human umbilical vein endothelial cells (HUVECs) were used to model the inflammatory microenvironment, and CCL18-induced angiogenesis was evaluated both in vitro and in vivo. We demonstrated that CCL18+ TAM infiltration positively associated with MVD in breast cancer samples, which was correlated with tumor metastasis and poor prognosis. We confirmed, both in vitro and in vivo, that CCL18 and VEGF synergistically promoted endothelial cell migration and angiogenesis. Conversely, blocking CCL18 or VEGF with neutralizing antibodies synergistically inhibited the promigratory effects of TAMs. Silencing PITPNM3, a putative CCL18 receptor, on the surface of HUVECs abrogated CCL18-mediated promigration and the enhancement of HUVEC tube formation, independently of VEGFR signaling. Moreover, CCL18 exposure induced the endothelial-mesenchymal transformation and activated ERK and Akt/GSK-3ß/Snail signaling in HUVECs, thereby contributing to its pro-angiogenic effects. In conclusion, our findings suggest that CCL18 released from TAMs promotes angiogenesis and tumor progression in breast cancer; thus, CCL18 may serve as a novel target for anti-angiogenic therapies.

[Expression and clinical significance of vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 in non-small cell lung carcinoma].

BACKGROUND & OBJECTIVE: Vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor receptor 3 (VEGFR-3) play important roles in lymphangiogenesis of malignant tumors; their expression are closely related to lymphatic metastasis of malignant tumors. This study was designed to investigate the expression and clinical significance of VEGF-C and VEGFR-3 in non-small cell lung cancer (NSCLC). METHODS: The expression of VEGF-C and VEGFR-3 in 77 specimens of NSCLC were detected by immunohistochemistry; their correlations to lymphatic vessel density (LVD), tumor size, histological type, differentiation, lymphatic metastasis, clinical recurrence, and survival time of the patients were analyzed. RESULTS: Positive rate of VEGF-C was 58% in NSCLC, and that of VEGFR-3 was 42%. The expression of VEGF-C protein was negatively correlated with the differentiation of NSCLC (r=-0.32, P=0.018). The expression of VEGF-C and VEGFR-3 were related to lymphatic metastasis, LVD, tumor size, and survival time of the patients. The expression of VEGF-C was positively related with that of VEGFR-3 (r=0.23, P=0.045). CONCLUSION: The expression of VEGF-C and VEGFR-3 are closely related with lymphatic metastasis and prognosis of NSCLC; their high expression indicate high risk of lymphatic metastasis and poor prognosis.

[Expression and significance of nitric oxide synthase mRNAs and proteins in giant cell tumors of bone].

BACKGROUND & OBJECTIVE: Recent studies have indicated that nitric oxide (NO) plays an important role in carcinogenesis and tumor progression. Activity of nitric oxide synthase (NOS) has been detected in normal bone cell lines. There was no report about relation of expression of NOS in giant cell tumors(GCT) of bone with its pathological grading and tumor recurrence. This study was designed to investigate the relationship amoung expression of NOS mRNAs, NOS proteins, pathological grading and tumor recurrence. METHODS: In situ hybridization (ISH) with cDNA probe was used to determine 14 frozen GCT specimens for constitutive NOS(cNOS) mRNA and inducible NOS(iNOS) mRNA. Immunohistochemical (IHC) staining with multiclonal antibodies was used to determine 42 paraffin-embedded GCT specimens for protein expression of NOS1, NOS2, and NOS3. RESULTS: (1)In 14 frozen GCT specimens, the positive expression rates of cNOS and iNOS mRNAs of multinuclear giant cells (MGC) were 78.6% and 57.1%; the positive expression rates of cNOS and iNOS mRNAs in mononuclear cells (MC) were both 35.7%. (2)The positive expression rate of cNOS mRNA in MGC of groups grading II and III was significantly higher than that of group grading I (P=0.008). (3) In 42 paraffin-embedded GCT specimens, the positive expression rates of NOS1, NOS2, and NOS3 protein were 85.7%, 59.5%, and 31.0% in MGC, 54.8%, 28.6%, and 14.3% in MC, respectively. (4)The positive expression rate of NOS1 protein in MC of groups grading II, III was significantly higher than that of group grading I (P=0.006). (5)The positive expression rate of NOS1 protein in MC of the recurrent group was significantly higher than that of the non-recurrent group (P=0.018). The positive expression rate of NOS3 protein in MGC of recurrent group was significantly higher than that of the non-recurrent group (P=0.041). CONCLUSION: The expression of NOS in GCT,especially cNOS in MC, is closely related to the pathological grading and the recurrence of GCT.