Combined large cell neuroendocrine carcinoma, lung adenocarcinoma, and squamous cell carcinoma: a case report and review of the literature.

BACKGROUND: Combined large cell neuroendocrine carcinoma (C-LCNEC) has a poor prognosis and there is no consensus about the treatment regimen for both LCNEC and C-LCNEC patients. CASE PRESENTATION: The patient was a 47-year-old female who received surgical resection. The postoperative histology and staging of the tumor suggested C-LCNEC with adenocarcinoma and squamous cell carcinoma and T2aN0M0 stage IB. Next-generation sequencing test showed KIF5B/RET fusion mutation without EGFR, ALK, RB1, and TP53 alterations. Adjuvant chemotherapy with 4-cycle docetaxel plus carboplatin was given and brain metastasis occurred after 10 months. CONCLUSIONS: C-LCNEC with adenocarcinoma and squamous cell carcinoma is rare and highly aggressive cancer. Surgical resection and adjuvant chemotherapy with SCLC regimen may improve the disease-free survival and overall survival. The accumulation of similar cases will clarify the profile and management of the disease.

Gene mutation landscape of a rare patient with acute megakaryoblastic leukemia after treatment of intracranial germ cell tumor.

Introduction: It was first reported that germ cell tumor patients suffer from hematologic malignancies 37 years ago. Since then, the number of relevant reports has increased each year, with most cases being mediastinal germ cell tumor. Theories have been proposed to explain this phenomenon, including a shared origin of progenitor cells, the effects of treatment, and independent development. However, up to now, no widely accepted explanation exists. The case with acute megakaryoblastic leukemia and intracranial germ cell tumor has never been reported before and the association is far less known. Methods: We used whole exome sequencing and gene mutation analysis to study the relationship between intracranial germ cell tumor and acute megakaryoblastic leukemia of our patient. Results: We report a patient who developed acute megakaryoblastic leukemia after treatment for an intracranial germ cell tumor. Through whole exome sequencing and gene mutation analysis, we identified that both tumors shared the same mutation genes and mutation sites, suggesting they originated from the same progenitor cells and differentiated in the later stage. Discussion: Our findings provide the first evidence supporting the theory that acute megakaryoblastic leukemia and intracranial germ cell tumor has the same progenitor cells.

Acute-onset paraneoplastic cerebellar degeneration secondary to neuroendocrine carcinoma with atypical prognosis: a case report.

Paraneoplastic cerebellar degeneration (PCD) is a neurological syndrome that is likely caused by tumor-induced autoimmunity against the cerebellum. Neuroendocrine carcinoma (NEC) is a type of neoplasm with high-grade malignant histology and biological behavior. The prognosis for both PCD and NEC is typically poor. We report a case of PCD secondary to metastatic NEC in the lymph nodes, with an unknown primary origin. The case presented acute cerebellar manifestations with typical neuroimaging findings, but with atypical prognosis after lymph node dissection. Neurological symptoms can provide clues to potential tumors, and early antitumor treatment may have contributed to the positive prognosis of PCD secondary to NEC in the present case.

Lung adenocarcinoma and sequential antineutrophil cytoplasmic antibody-associated vasculitis: a case report.

The relationship between antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and lung cancer remains unclear. A 66-year-old man presented with pulmonary nodules. Histological examination of a specimen from computed tomography-guided percutaneous transthoracic biopsy revealed adenocarcinoma. The patient was treated using cryoablation and systemic chemotherapy. Sixteen months later, the patient presented with fever, nasal inflammation, recurrent lung lesions, elevated serum creatinine levels, and high levels of ANCA. Histological examination of a specimen from ultrasound-guided percutaneous renal biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis. The patient responded to treatment, but granulomatosis with polyangiitis recurred and he later died. This case highlights the possibility of sequential AAV with lung cancer. Although this is relatively rare, further research is needed to better understand the association or pathophysiological link between lung cancer and AAV.

Extensive multifocal and pleomorphic pulmonary lesions in Waldenström macroglobulinemia: A case report.

BACKGROUND: Waldenström macroglobulinemia (WM) is a type of small lymphocytic lymphoma that mainly affects the bone marrow, spleen, and lymph nodes. A subset of patients with WM demonstrates extramedullary involvement (4.4%), and the most frequent extramedullary disease site involved is the lungs (30%). CASE SUMMARY: A 60-year-old male patient who experienced intermittent breath-holding for 6 mo was admitted on August 14, 2017. Chest computed tomography indicated multiple pulmonary cavities in the upper lobes of both lungs, with pulmonary consolidation, ground-glass opacities, patchy infiltrates, fibrous bands, large bullae, and enlarged lymph nodes in the mediastinum. The patient was a heavy smoker (20 cigarettes/d for 40 years). Diagnostic fiberoptic bronchoscopy revealed normal findings. Serological examination revealed a remarkable increase in serum immunoglobulin M levels (30.24 g/L; normal: 0.4-2.30 g/L). A computed tomography-guided percutaneous pulmonary biopsy was performed in the left lower lobe of the lung with pulmonary consolidation and indicated that the alveolar structure disappeared and that a large amount of amyloid-like deposition was present along with the infiltration of very few lymphocytes and plasma cells. The patient was treated with the combined treatment of dexamethasone + rituximab + lenalidomide over four courses. Serum immunoglobulin M did not normalize, and he received ibrutinib + dexamethasone. CONCLUSION: This patient with WM and lung amyloidosis had a wide range of pulmonary lesions and a variety of morphological features, which was a rare case. Yet, some changes might be ascribed to heavy smoking.

Diagnostic value of high b-value (2000 s/mm2) DWI for thyroid micronodules.

The aim of the study was to assess the diagnostic value of high b-value (2000 s/mm) diffusion-weighted imaging (DWI) in differentiating malignant from benign thyroid micronodules.Consecutive patients with thyroid micronodules scheduled for Ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) or surgery were underwent high b-value DWI with 3 b-values: 0, 800, and 2000 s/mm. Signal intensity ratios (SIRs) of thyroid micronodules to adjacent normal thyroid tissue on DWI were measured as SIRb0, SIRb800 and SIRb2000. Apparent diffusion coefficients (ADCs) according to the three different b-values were acquired as: ADCb0-800, ADCb0-2000 and ADCb0-800-2000. The 6 diagnostic indicators were evaluated by receiver operating characteristic (ROC) and diagnostic ability was compared between the high b-value DWI and US.Sixty-two malignant thyroid micronodules (48 patients, 13 men and 35 women, aged 44.8 ±â€Š11.7 years) and 57 benign thyroid micronodules (40 patients, 6 men and 34 women, aged 49.6 ±â€Š12.5 years) were enrolled into the final statistical analysis. Among the alone diagnostic indicators, SIRb2000 had the highest diagnostic ability in differentiating malignant from benign thyroid micronodules with area under curve (AUC) of 0.975, sensitivity of 90.32% and specificity of 96.49%. Compared to US, SIRb2000 had a significantly better diagnostic ability US for thyroid micronodules (P < .001) with dramatically raised positive predict value (96.6% vs 78.9%) and reduced false-positive rate (3.51% vs 26.32%).High b-value (2000 s/mm) DWI can contribute to differentiating malignant from benign thyroid micronodules.

Utility of high b-value (2000 sec/mm2) DWI with RESOLVE in differentiating papillary thyroid carcinomas and papillary thyroid microcarcinomas from benign thyroid nodules.

PURPOSE: The aim of the study was to evaluate the role of high b-value (2000 sec/mm2) diffusion-weighted imaging (DWI) by using Readout Segmentation of Long Variable Echo-trains (RESOLVE) in differentiating papillary thyroid carcinomas (PTCs) and papillary thyroid microcarcinomas (PTMCs) from benign thyroid nodules. MATERIALS AND METHODS: Consecutive patients with thyroid nodules scheduled for surgery underwent high b-value DWI with 3 b-values: 0, 800 and 2000 sec/mm2. Signal intensity ratios (SIRs) of thyroid nodules to adjacent normal thyroid tissue on DWI were measured as: SIRb0, SIRb800 and SIRb2000. Apparent diffusion coefficient (ADC) values based on the 3 different b-values were acquired as: ADCb0-800, ADCb0-2000, and ADCb0-800-2000. The 6 diagnostic indicators were evaluated by receiver operating characteristic (ROC) and diagnostic ability was compared between high b-value DWI and Ultrasound (US). RESULTS: A total of 52 PTCs including 33 PTMCs (38 patients, 8 men and 30 women, aged 45.68 ± 11.93 years) and 62 benign thyroid nodules (46 patients, 7 men and 39 women, aged 48.73 ± 11.98 years) were enrolled into the final statistical analysis. ADCb0-800-2000 had the highest diagnostic ability in differentiating PTCs from benign thyroid nodules with area under curve (AUC) of 0.944, sensitivity of 96.15% and specificity of 85.48%, and PTMCs from benign thyroid nodules with AUC of 0.940, sensitivity of 93.94% and specificity of 85.48%. On the strength of lower false-positive rates than US (14.52% vs. 32.26% for PTCs and 14.52% vs. 32.26% for PTMCs), ADCb0-800-2000 had significantly better diagnostic ability in PTCs (P = 0.002) and PTMCs (P = 0.005). CONCLUSION: High b-value (2000 sec/mm2) DWI can contribute to differentiating PTCs and PTMCs from benign thyroid nodules and can be potentially used as an active surveillance imaging method for PTMCs.

CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells.

Trastuzumab is widely used in the clinical treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer, but the patient response rate is low. CD147 stimulates cancer cell proliferation, migration, metastasis and differentiation and is involved in chemoresistance in many types of cancer cells. Whether CD147 alters the effect of trastuzumab on HER2-positive breast cancer cells has not been previously reported. Our study confirmed that CD147 suppression enhances the effects of trastuzumab both in vitro and in vivo. CD147 suppression increased the inhibitory rate of trastuzumab and cell apoptosis in SKBR3, BT474, HCC1954 and MDA-MB453 cells compared with the controls. Furthermore, CD147 knockdown increased expression of cleaved Caspase-3/9 and poly (ADP-ribose) polymerase (PARP) and decreased both mitogen-activated protein kinase (MAPK) and Akt phosphorylation in the four cell lines. In an HCC1954 xenograft model, trastuzumab achieved greater suppression of tumor growth in the CD147-knockdown group than in the shRNA negative control (NC) group. These data indicated that enhancement of the effect of trastuzumab on HER2-positive cells following CD147 knockdown might be attributed to increased apoptosis and decreased phosphorylation of signaling proteins. CD147 may be a key protein for enhancing the clinical efficacy of trastuzumab.

Epithelioid inflammatory myofibroblastic sarcoma in abdominal cavity: a case report and review of literature.

In this study, we present a rare and difficult case of epithelioid inflammatory myofibroblastic sarcoma (EIMS) in abdominal cavity. A 47-year-old female presented as left upper abdominal pain for 6 months and abdominal distention for 1 month. CT examination showed a solid mass in the left upper intra-abdomen. Grossly, the tumor was found in the mesenterium of colon with the size of 7.5 × 6.5 × 3.5 cm, and was solid and gray-yellowish in the cut surface. Focal myxomatous appearance was observed. Microscopically, stromal myxoid change together with prominant infiltrated lymphocytes, neutrophils and eosinophils were found in the tumor, and the tumor cells were round, epithelioid with vesicular nuclei, large prominant nucleoli and high mitotic rate. Immunohistochemically, strong diffused positive for vimentin, desmin, ALK (nuclear membrane staining pattern) and AAT, focally positive for CD99 and CD30, were showed, Ki67 index was about 20%; Especially, WT-1 and D240 were focally expressed in this tumor. FISH analysis showed rearrangement of ALK, and reverse-transcription polymerase chain reaction (RT-PCR) analysis was used to detect the fusion location of the RANBP2 and ALK gene. The diagnosis of EMIS was made based on its location, typical morphology, the immunohistochemical features especially the nuclear membranous immunostaining of ALK and rearrangement of RANBP2-ALK. The tumor showed higher aggressive behaviors and a poor prognosis. The differential diagnosis and other treatments of EMIS are also discussed in the present study. This finding may increase the case information of EMIS.

Serial Diffusion-Weighted and Conventional MR Imaging in Primary Cerebral Neuroblastoma Treated with Radiotherapy and Chemotherapy. A Case Report and Literature Review.

Primary cerebral neuroblastoma is a rare malignant tumor encountered most commonly in children. The radiological features of this entity are variable and rarely reported. The diffusion-weighted imaging (DWI) findings have not previously reported. We describe serial DWI and conventional MRI in a case of primary cerebral neuroblastoma to assess the imaging features and the role of DWI for monitoring chemoradiotherapy response.

Expression of Y-Box-binding protein 1 in Chinese patients with breast cancer.

The purpose of this study was to investigate the expression of Y-Box-binding protein 1 (YB-1) in breast cancer and its correlation with clinicopathological characteristics and prognosis. Paraffin sections were retrospectively collected from 239 cases of stage I-III breast cancer patients and 30 healthy females who received surgery between January 2000 and December 2004 in the Chinese People's Liberation Army General Hospital. The protein expression of YB-1 was detected by immunohistochemistry. The expression difference between the two groups and the correlation between YB-1 expression and clinicopathological characteristics and breast cancer prognosis were analyzed. Within the breast cancer group, YB-1 was expressed in the cytoplasm in 100.0% (239/239) of cases and in the nucleus in 36.8% (88/239) of cases. Within the control group of normal breast tissue, YB-1 was expressed in the cytoplasm in 100.0% (30/30) of cases and in the nucleus in 16.7% (5/30) of cases. The expression of YB-1 in the nucleus of breast cancer cells was significantly higher than that in normal breast tissue (P = 0.029). The expression of YB-1 in the nucleus of breast cancer cells positively correlated with the Scarff-Bloom-Richardson grade (P = 0.007) and HER-2 expression (P = 0.005), negatively correlated with ER expression (P = 0.004), and was independent of the age, menstrual status, pathological type, tumor size, lymph node status, presence of thrombosis, PR expression, and EGFR expression. The 5-year disease-free survival (DFS) and overall survival (OS) of patients with positive YB-1 expression in the nucleus were significantly lower than those of patients who were negative for nuclear YB-1 expression, and the difference was statistically significant (DFS 65.9% vs. 82.1%, P = 0.000; OS 79.5% vs. 92.1%, P = 0.000). Multivariate analysis suggested that the expression of YB-1 in the nucleus is an independent prognostic factor that affects DFS and OS in breast cancer patients (DFS P = 0.015; OS P = 0.035). In conclusion, the expression of YB-1 in the nucleus is related to carcinogenesis and the development of breast cancer. Therefore, YB-1 is an important molecular marker that can be used to predict breast cancer prognosis.

[Serrated lesions of colon and their malignant potential].

OBJECTIVE: To study the serrated lesions of colon and to compare the malignant potential between traditional serrated adenomas (TSA) and conventional adenomas (CAD). METHODS: A total of 5347 cases of colorectal polyps encountered in five regional hospitals during a five-year period were retrospectively reviewed. The serrated lesions were classified on the basis of histologic examination. One hundred and eighty-seven cases of CAD (including 160 cases of tubular adenoma and 27 cases of villous adenoma) and 36 cases of invasive adenocarcinoma were randomly selected as the controls. The degree of dysplasia and expressions of Ki-67, p53 and beta-catenin in TSA and CAD were compared. RESULTS: Amongst the 5347 colorectal polyps studied, 258 cases (4.8%) of serrated lesions were found, which included 112 cases (43.4%, 112/258) of hyperplastic polyp, 78 cases (30.2%, 78/258) of TSA and 26 cases (10.1%, 26/258) of sessile serrated adenoma. Sixty-two cases of TSA were identified from 3 hospitals, in which moderate dysplasia was found in 13 cases. High-grade intraepithelial neoplasia and ICA were found in 6 cases (9.6%). Compared with the 187 cases of CAD, moderate dysplasia were found in 27 cases and high-grade intraepithelial neoplasia and invasive adenocarcinoma were found in 25 cases (13.3%, χ(2) = 19.373, P = 0.000). There was statistically significant difference between TSA and CAD in the degree of dysphasia. The expression of Ki-67, p53 and beta-catenin in TSA and CAD showed no significant difference (P > 0.05). CONCLUSIONS: The incidence of serrated lesions is lower in northern Chinese population than that in Caucasians. TSA has obvious malignant potential; but the rate associated with high-grade intraepithelial neoplasia and invasive adenocarcinoma is lower than that in CAD.

[PAR-1 regulation of intracellular Ca²(+) mobilization in pulmonary giant cell carcinoma cell line PLA801D/PLA801C].

OBJECTIVES: To investigate molecular mechanisms of PAR-1 regulation on intracellular Ca²(+) mobilization in lung giant cell carcinoma cells in vitro and its involvement in tumor metastasis. METHODS: Free intracellular Ca²(+) ([Ca²(+)]i) was measured in lung giant cell carcinoma PLA801C and PLA801D cells by confocal microscopy. Sense and anti-sense PAR-1 expression vectors were transfected into PLA801C (C+)and PLA801D(D-) cells, respectively. The effects of PAR-1 expression were investigated by thrombin and TRAP-induced mobilization of [Ca²(+)]i in the C+ and D-cells. RESULTS: There were significant differences of the mean values of [Ca²(+)]i between PLA801D (59.55) and PLA801C cells (35.46, P < 0.01). The mean [Ca²(+)]i of C+ cells (45.77) was significantly higher than that of its control CV cells (35.46, P < 0.05), and the mean [Ca²(+)]i of D-cells (48.42) was significantly lower than that of its control DV cells (59.55, P < 0.05). The peaks of [Ca²(+)]i of C+ and CV cells were 48.19 ± 9.84 and 45.64 ± 9.87 (P < 0.05) respectively at 80 s and 100 s after thrombin treatment, but were 111.31 ± 25.00 and 52.93 ± 11.21 (P < 0.05) respectively at 60 s after TRAP treatment. The peaks of [Ca²(+)]i of D- and DV cells were 40.71 ± 5.89 and 61.07 ± 21.36 (P < 0.05) respectively at 60 s after thrombin treatment, but were 84.98 ± 11.23 and 102.58 ± 21.48 (P < 0.05) respectively at 40 s after TRAP treatment. CONCLUSIONS: The high metastatic potential of PLA801D and PLA801C may be related to [Ca²(+)]i of the tumor cells. PAR-1 may play an important role in the metastasis of lung giant cell carcinoma cells by up-regulating the intracellular Ca²(+).

[Functional aspects of protease-activated receptor 1 in promoting metastasis of lung cancer].

OBJECTIVE: To study the functional aspects of protease-activated receptor 1 (PAR-1) gene involved in tumor metastasis. METHODS: Two human lung giant cell carcinoma cell lines PLA801C (low metastasis potential) and PLA801D (high metastasis potential) were chosen as in-vitro human cancer model systems. Sense and anti-sense expression constructs of PAR-1 gene (pC/PAR1s and pC/PAR1as) were transfected into PLA-801C and PLA-801D cells by lipofection. PAR-1 expression was determined by RT-PCR and western blot analysis. MTT growth, flow cytometry analysis, fibronectin adhesion, and matrigel invasion assays were used to study the effect of PAR-1 expression on the proliferation, adhesion, and invasion of the transfected cells. RESULTS: Appropriate up-regulation or down-regulation of protein expression of PAR-1 was observed in both transfected cell lines (PLA801C and PLA801D) to express PAR-1s or PAR-1as, respectively. Expression of the sense PAR-1 markedly increased cellular proliferation, adhesion and invasion of PLA-801C cells. In contrast, anti-sense PAR-1 significantly inhibited cell growth, adhesion and invasion capabilities, along with cell arrest at G0/G1 phase of the PLA-801D cells. CONCLUSIONS: Successful up- and down- regulation of expression of PAR-1 can be achieved by in-vitro transfection of sense and antisense PAR-1 constructs. PAR-1 may enhance metastasis of lung cancer through its regulation of cellular proliferation, adhesion and invasion. Down-regulation of expression of PAR-1 may provide a new therapeutic strategy against lung carcinoma.

[Expression of PAR-1 in human lung carcinoma and its relationship with tumor metastatic potential].

OBJECTIVE: To explore the correlation between expression of PAR-1 and metastasis of human lung carcinoma. METHODS: Expression levels of PAR-1 were examined in surgically resected lung carcinoma specimens and corresponding lymph nodes by RT-PCR and immunohistochemistry, combined with morphometric methodology and clinicopathologic profiles. RESULTS: Strong PAR-1 staining was detected in the periphery of carcinoma nests, adenocarcinomatous emboli, foci of atypical adenomatous hyperplasia adjacent to the adenocarcinoma and atypical proliferation of duct epithelium of bronchial mucous glands. The expression rates of PAR-1 were 73.8% (59/80) and 63.9% (23/36) by immunohistochemistry and RT-PCR respectively. The percentage of PAR-1 protein expression cells was significantly higher in tumors with metastasis (85.7%, 48/56) than those without (45.8%, 11/24). Morphometric study demonstrated that there were significant differences of PAR-1 protein expression levels between tumors with metastatic and those without, primary and metastatic carcinomas, primary carcinomas and benign lung tissues adjacent to the carcinoma. No significant correlation was found between PAR-1 expression level and tumor size, histological types and tumor grades. The positive rate of PAR-1 mRNA expression in the metastatic group was significantly higher than that of the non-metastatic group (78.3%, 18/23 v.s. 38.5%, 5/13). CONCLUSION: PAR-1 expression may play an important role in determining the malignant phenotypes of lung cancers and significantly contribute to their initiation, progression and metastasis.

[Expression of PH20 in primary and metastatic breast cancer and its pathological significance].

OBJECTIVE: To evaluate the expression pattern of PH20 in primary and metastatic breast cancer and its relationship to tumor metastatic potential. METHODS: Anti-PH20 antibody was synthesized by injection of conjugated human PH20 peptides into rabbits. Immunohistochemical study was performed on 53 cases of human breast cancer. Western blot was used to detect PH20 expression in 5 cases of breast cancer with available fresh tissue. Two oligonucleotide probes were prepared for in-situ hybridization using breast tissue microarray. RESULTS: Normal breast tissue did not express PH20 (0/3), while 58.4% (31/53) of breast cancer cases did. The highest expression rate was found in metastatic foci in regional lymph nodes (83.3%), followed by primary breast cancer tissue in cases with lymph node secondaries (70.8%). The breast cancer cases with no any metastasis had an expression rate of 48.2%. The immunohistochemical staining results were further confirmed by Western blotting. In-situ hybridization showed PH20 RNA in 75% of the breast cancer tissue (21/28). Two of the 17 cases of normal breast tissue showed weak expression in some ductolobular units. CONCLUSIONS: The expression of PH20 has a positive correlation with metastatic potential in breast cancer. It is possible that PH20 may play an important role in the invasive growth and metastasis of breast cancer cells, via mechanisms such as digestion of surrounding stromal tissue and release of FGF-2.

[Transplantation of fetal cardiomyocyte regenerates infarcted myocardium in rats].

OBJECTIVE: To investigate the feasibility and efficiency of fetal cardiomyocyte transplantation into the rat model of myocardial infarction. METHODS: Cardiomyocytes were isolated from aborted human embryos aged 12 - 16 weeks and cultured for 5 days to confirm their viability. Rat model of extensive myocardial infarction (MI) was established in 18 male Wistar rats by ligating the descending anterior branch of left coronary artery and the 18 rats were randomly divided into 2 groups: transplantation group (n = 7, 2 x 10(6) fetal cardiomyocytes were transplanted into the myocardial scar) and culture medium injection group (n = 6, culture medium was injected into the myocardial scar) 5 days after extensive MI was caused. Another 6 rats undergoing sham operation were used as controls. Echocardiography was performed before and 60 +/- 3 days after the implantation to assess the left ventricular (LV) remodeling and cardiac function. Then the rats were killed and their heart were harvested to undergo HE staining, immunohistochemical examination with antibody against human alpha-actin smooth muscle (SMA) isoform, and light microscopy. RESULTS: Light microscopy revealed the presence of engrafted human fetal cardiomyocytes in the infarcted myocardium and the presence of nascent intercalated disks connecting the engrafted fetal cardiomyocytes and the host myocardium. The engrafted fetal cardiomyocytes were SMA positive. Serial echocardiography revealed that cell transplantation prevented scar thinning, LV further dilatation and dysfunction while the control animals developed scar thinning, significant LV dilatation accompanied by progressive deterioration in LV contractility. CONCLUSION: Fetal cardiomyocytes can be implanted and survive in the infarcted myocardial cells, thus preventing the scar thinning, and LV further dilatation and dysfunction.

Extracellular matrix protein 1 (ECM1) is over-expressed in malignant epithelial tumors.

The extracellular matrix protein 1 (ECM1) is a secreted protein that has been implicated with cell proliferation, angiogenesis and differentiation. In the present study, we used immunohistochemical staining to examine the expression of ECM1 in a panel of human tumors and found that it was closely correlated with some types of tumors including: invasive breast ductal carcinoma (83%), esophageal squamous carcinoma (73%), gastric cancer (88%) and colorectal cancer (78%). Significantly, ECM1expression was correlated with the metastatic properties of the tumors. Primary breast cancers that had formed metastases were 76% positive while those that had not metastasized were only 33% positive. ECM1 expression was also correlated with PCNA a marker for proliferation, but not with CD34, a marker for endothelial cells. These results indicate that ECM1 tends to be preferentially expressed by metastatic epithelial tumors.