Insidious malignant triton tumor of the chest wall with late flare-up.

Malignant triton tumor is a rare malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation. Most of these tumors are located in the head, neck, and extremities, and about half of cases are associated with neurofibromatosis type 1 featuring cafe-au-lait spots or cutaneous neurofibromas. We present a 76-year-old man with an insidious chest wall tumor with late progressive painful enlargement and pleural and pulmonary involvement. Complete resection of the affected thoracic wall as well as single separate lesions in the parietal pleura and left upper lung was carried out. The pathological examination confirmed that it was a malignant triton tumor. The patient received adjuvant chemo-radiotherapy but eventually succumbed to disease relapse and distant metastases 6 months after the surgery.

A case of dermatomyositis with secondary Sjögren's Syndrome-diagnosis with follow-up study of technetium-99m pyrophosphate scintigraphy.

PURPOSE: To report a case of dermatomyositis (DM) with secondary Sjögren's syndrome (SS) and propose the clinical application of technetium-99m pyrophosphate ((99m)Tc-PYP) scan. CASE REPORT: A 50-year-old woman had progressive proximal muscle weakness of bilateral thighs, myalgia, tea-colored urine, and exercise intolerance for 6 months. Physical examination showed malar rash, V-sign, periungual erythema, and mechanic hands. Neurological assessment showed symmetric pelvic-girdle weakness, myopathic face, waddling gait, but preserved deep tendon reflex and sensory functions. DM was diagnosed on the basis of typical rashes and serum creatinine kinase elevation (7397 IU/L). Aside from myopathic symptoms, dry eye and mouth were reported. Thorough autoantibody searches showed positive anti-SSA/Ro antibody (198 U/ml). Both Schirmer's test and sialoscintigraphy were positive, leading secondary SS as diagnosis. Initial (99m)Tc-PYP scan revealed increased radiouptake in the muscles of bilateral thighs, compatible with clinical assessment. Followup scan three months later shows abnormal but attenuated radiouptake at bilateral thighs, in the presence of nearly-complete clinical recovery. CONCLUSION: DM with secondary SS in adult is a unique disease entity, with predominantly myopathic symptoms and satisfactory therapeutic response as its characteristics. Our serial muscle imaging studies suggest that (99m)Tc-PYP scan is at once anatomically-specific and persistently-sensitive to microstructural damages within inflammatory muscles, enabling clinician to monitor disease activity and therapeutic response.

Synergistic anticancer activity of triptolide combined with cisplatin enhances apoptosis in gastric cancer in vitro and in vivo.

Cisplatin is an anticancer agent that is effective against several types of cancer, including gastric cancer. However, its therapeutic application is limited by its toxicity in normal tissues and complications caused in patients. In this study, we attempted to clarify how triptolide, an active component extracted from the traditional Chinese herbal medicine Tripterygium wilfordii Hook F (TWHF), enhances cisplatin-induced cytotoxicity in gastric cancer SC-M1 cells. After low-dose combined treatments with triptolide and cisplatin, a decrease in viability with a concomitant increase in apoptosis was observed in SC-M1 cells but not in normal cells. Apoptosis induced by the combined treatments was accompanied by loss of mitochondrial membrane potential and release of cytochrome c. Triptolide increased the cisplatin-induced activation of caspase-3 and caspase-9 and the downstream cleavage of PARP in SC-M1 cells. Results of these in vitro experiments indicated that triptolide enhanced cytotoxicity in cisplatin-treated SC-M1 cells and that this effect is mediated by apoptosis through a mitochondrial pathway. Furthermore, using a SCID mouse xenograft model, we demonstrated that the combined treatment completely suppressed tumor growth via down-regulation of proliferating cell nuclear antigen expression without significant side effects. These results suggest that lower concentrations of cisplatin and triptolide used in combination may produce a synergistic anticancer effect that warrants further investigation for its potential clinical applications.

Widespread expression of prostate apoptosis response-4 in nasopharyngeal carcinoma.

BACKGROUND: Prostate apoptosis response-4 (Par-4) augments apoptosis in various tumors, either during apoptotic insult or by ectopic overexpression. However, investigation of Par-4 expression in nasopharyngeal carcinoma (NPC) is lacking. METHODS: Specimens from patients with NPC, hypopharyngeal carcinoma (HPC), or oral cavity cancer were examined for Par-4 expression using immunohistochemistry. NPC cell proliferation and apoptosis were analyzed using immunohistochemical staining for Ki67, B-cell lymphoma 2 (Bcl-2), and in situ terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick end-labeling (TUNEL) assay, respectively. RESULTS: Par-4 was ubiquitously expressed in NPC biopsies (96.2%, 25/26) and was significantly higher than in HPC (47.6%, 50/105, p < .0001) and oral cavity cancers (38.7%, 12/31, p < .0001). Remarkably, apoptosis of NPC cells was absent and Par-4 expression was associated with obvious expression of Bcl-2 and Ki67 in all patients tested with NPC. CONCLUSIONS: Immunohistochemistry results showed widespread expression of Par-4 in NPC and revealed sustainable proliferation of NPC cells regardless of Par-4 expression.

The clinicopathological analysis of 303 cases with malignant lymphoma classified according to the World Health Organization classification system in a single institute of Taiwan.

Several reports have shown a different distribution of malignant lymphoma (ML) in Asian and Western populations. The purpose of our survey was to elucidate whether there are substantial differences in the frequencies of subtypes of ML between different geographical areas. All entities diagnosed as ML between June 1995 and December 2007 were selected according to the 2008 World Health Organization (WHO) classification and searched for clinical outcomes. The cases were retrieved and reviewed by a panel of clinical haematologists and haematopathologists. A total of 303 patients with ML were identified for retrospective analysis. Of the 303 patients with ML, 278 patients (91.7%) had non-Hodgkin's lymphoma (NHL), and 25 (9.2%) had Hodgkin's lymphoma. Of the 278 patients with NHL, 223 (73.6%) had lymphoma of B-cell lineage, and 55 (18.1%) had lymphoma of T-cell lineage. One hundred and thirty-seven patients were diagnosed with diffuse large B-cell lymphoma, which was the most common B-cell lineage subtype and accounted for 45.2% of patients with NHL. Peripheral T-cell lymphomas were the most frequent subset of the T-cell neoplasms, comprising 10.6% of ML. Extranodal involvement was found in 125 (44.9%) of the 278 patients with NHL, and the lymph node was the site of primary involvement in 153 patients (55.1%). Fifty-nine (47.2%) of the 125 patients with extranodal presentation had gastrointestinal tract involvement. Outcome was worse in patients with extranodal NHL than in those with nodal NHL through the entire follow-up period; the difference in survival rates was significant. Our findings clarify the applicability and prognostic relevance of the WHO classification system and provide further information about the incidence of various lymphoma subtypes in Taiwan. Primary extranodal NHL was associated with a worse prognosis and distinct characteristics compared with nodal NHL. The outcome of different types of extranodal NHL should be investigated further.

Expression of Epstein-Barr nuclear antigen 1 in gastric carcinoma cells is associated with enhanced tumorigenicity and reduced cisplatin sensitivity.

Epstein-Barr nuclear antigen 1 (EBNA-1) is consistently expressed in all EBV-associated gastric carcinomas. We explored its biological effects in gastric carcinoma cells by expressing the protein in two Epstein-Barr virus (EBV)-negative gastric carcinoma cell lines (SCM1 and TMC1). EBNA1-expressing SCM1 and TMC1 cells displayed no significant differences in growth rates, respectively, compared to those of vector-transfected SCM1 and TMC1 cells in vitro. However, EBNA1 was able to enhance tumorigenicity, the growth rate and the malignant histopathological grade in a xenograft nude mice test. We also evaluated whether EBNA1 caused EBNA1-expressing cells to have enhanced tumorigenicity in an immunocompetent host. We showed that EBNA1-expressing LL/2 cells (derived from lung carcinoma of a Swiss mouse) had enhanced tumorigenicity and growth ability in the immunocompetent allograft Balb/c mice test. These results support the expression of EBNA1 in EBV-associated gastric carcinoma being able to provide advantages of EBV-mediated cell growth and transformation, and to enhance the malignant potential in vivo. In a clonogenic assay, we showed that EBNA1 could reduce the sensitivity of gastric carcinoma cells (SCM1 cells) harboring wild-type p53 to cisplatin, but this was not found in mutant p53-bearing TMC1 cells. In addition, we demonstrated that EBNA1-expressing SCM1 cells, but not EBNA1-expressing TMC1 cells, were associated with reduced expression levels of p53. These findings are compatible with EBNA1 efficiently competing with p53 for binding to ubiquitin-specific protease 7, which causes p53 to degrade by the ubiquitin/proteasome system. These findings suggest that EBNA1 expression is able to reduce the p53 protein level, resulting in the inhibition of its functional activities. Finally, our results suggest that EBV infection with EBNA1 expression in gastric carcinomas provides advantages for host cell survival, growth ability and transformation potential involving escape from immunosurveillance and a reduction in the sensitivity to DNA damage or other apoptotic stress stimuli mediated by suppression of the wild-type p53 protein level; these are distinct from the pathogenesis of EBV-negative gastric carcinomas.

Primary spinal epidural Ewing sarcoma: a case report and review of the literature.

Primary extraosseous Ewing sarcoma is a rare entity, especially in the spinal epidural site. Less than 20 cases have been reported in the literature. Here, we present a previously healthy 12-year-old boy who complained of low back pain, progressive gait disturbance and weakness of right lower extremity for nearly one month before admission. Magnetic resonance imaging showed one solitary posterior extradural mass, measuring 4 x 2.2 x 2.1 cm, with severe cord compression at the level from T7 to T9. The mass appeared hypo-intense on both T1-weighted and T2-weighted images and homogeneous contrast enhancement after injection of gadolinium. He underwent laminectomies of T8 and T9 and complete resection of the tumor. The pathology confirmed a diagnosis of Ewing sarcoma after immunohistochemical staining. His profound neurological deficits recovered well and no recurrence was discovered after adjuvant chemotherapy and radiotherapy. The relevant literature is reviewed and the limited cases are also analyzed.

Association of cortactin, fascin-1 and epidermal growth factor receptor (EGFR) expression in ovarian carcinomas: correlation with clinicopathological parameters.

Cortactin, fascin-1 and EGFR are recognized as important factors in tumor progression. We tested the hypothesis that cortactin, fascin-1 and EGFR expression correlates with clinicopathological parameters of the four most common ovarian surface epithelial carcinomas--serous cystadenocarcinoma, mucinous cystadenocarcinoma, endometrioid adenocarcinoma, and clear cell carcinoma. Immunohistochemical analysis of cortactin, fascin-1 and EGFR was performed using tissue microarrays of 172 specimens comprising 69 serous cystadenocarcinomas, 44 mucinous cystadenocarcinomas, 45 endometrioid adenocarcinomas and 14 clear cell carcinomas. All ovarian carcinomas showed significant expression of cortactin, fascin-1 and EGFR in staining intensity, tumor percentages and immunostaining scores. In addition, higher immunostaining scores of fascin-1 correlated with more advanced cancer stages (TNM), poorer histological differentiation and poorer survival rate of mucinous cystadenocarcinoma. Similarly, higher immunostaining scores of cortactin correlated with T stages and histological differentiation of serous cystadenocarcinoma. The immunostaining scores of EGFR did not correlate with TNM stages, tumor differentiation or prognosis in the four ovarian surface epithelial carcinomas. Our findings suggest that cortactin and fascin-1 may serve as good biomarkers in evaluating aggressiveness of ovarian serous and mucinous cystadenocarcinoma. And the pharmacological inhibitors of fascin-1 activity may slow down tumor progression and prolong survival time in patients with mucinous cystadenocarcinoma.

Primary malignant fibrous histiocytoma of the thyroid: review of the literature with two new cases.

Primary malignant fibrous histiocytoma of thyroid is extremely rare. Only three cases have been reported. We report two cases of this rare disease. Case 1 was a 70-year-old woman who had Graves' disease and a growing 3.5-cm thyroid nodule with constrictive symptoms. Fine-needle aspiration cytology showed suspicious atypical cells. She had a total thyroidectomy; frozen section showed sarcoma. Final pathology showed malignant fibrous histiocytoma. Case 2 was a 67-year-old woman who had a 5-cm thyroid nodule that rapidly grew, causing tracheal deviation. A diagnostic lobectomy and pathology showed malignant fibrous histiocytoma. She then had a completion total thyroidectomy. Neither patient had metastatic lesions found by whole body gallium scans, computerized tomographic scans, and neck sonography. Both patients had postoperative radiotherapy and were alive and without recurrence at 6 months follow-up.

Matriptase and survivin expression associated with tumor progression and malignant potential in breast cancer of Chinese women: tissue microarray analysis of immunostaining scores with clinicopathological parameters.

OBJECTIVE: The aim of this study was to examine the expression of matriptase and survivin in breast carcinoma and correlate with clinicopathological parameters. METHODS: Immunohistochemical analysis of matriptase and survivin were performed in tissue microarray slides of 290 cases, including 11 normal breast tissue; 27 fibrocystic disease; 17 fibroadenoma; 6 atypical ductal hyperplasia; 39 ductal carcinoma in situ, low grade (DCIS, low grade); 39 ductal carcinoma in situ, high grade (DCIS, high grade); 27 invasive ductal carcinoma, grade I (IDC, grade I); 78 invasive ductal carcinoma, grade II (IDC, grade II); and 46 invasive ductal carcinoma, grade III (IDC, grade III). RESULTS: The average immunostaining scores of matriptase were 44.1 in normal breast tissue, 52.7 in fibrocystic disease, 76.5 in fibroadenoma, 81.7 in atypical ductal hyperplasia, 133.7 in low-grade DCIS, and 155.8 in high-grade DCIS. Among 151 breast IDC cases, the average immunostaining scores of matriptase were 172.7 in grade I, 211.7 in grade II, and 221.2 in grade III. Additionally, the average immunostaining scores of surviving also correlate with tumor grades and stages. CONCLUSIONS: Higher expressions of matriptase and survivin correlate significantly with clinicopathological parameters in breast cancer and the malignant potential in premalignant lesions. In addition, higher survivin expression had poorer prognosis of breast IDC cases.

EMMPRIN and fascin overexpression associated with clinicopathologic parameters of pancreatobiliary adenocarcinoma in Chinese people.

The aim of this study was to test whether expression of EMMPRIN and fascin correlates with clinicopathologic parameters of pancreatobiliary adenocarcinoma. Immunohistochemical analysis of EMMPRIN and fascin was performed in 100 surgical specimens obtained from Chinese patients, including 18 well-differentiated, 62 moderately differentiated, and 20 poorly differentiated pancreatic and biliary adenocarcinomas. Neither EMMPRIN nor fascin was detectable in normal pancreatic and biliary glandular epithelia. However, EMMPRIN and fascin immunoreactivity was observed on the cell membrane and within the cytoplasm in pancreatobiliary adenocarcinomas. Higher immunostaining scores of EMMPRIN and fascin were strongly associated with advanced grades of pancreatobiliary adenocarcinomas (36.1 and 51.3 for grade I, 95.5 and 110.1 for grade II, and 133.7 and 165.8 for grade III). In addition, higher immunostaining scores of EMMPRIN and fascin were associated with advanced T stages (29.8 and 43.6 for T1, 86.3 and 93.2 for T2, 107.6 and 117.6 for T3, and 129.5 and 156.5 for T4). Higher EMMPRIN and fascin scores were associated with shorter survival times and more advanced M and N stages of pancreatiobiliary adenocarcinomas. A higher expression of EMMPRIN and fascin was found to correlate well with histologic grades and clinical stages of pancreatobiliary adenocarcinomas.

Matriptase expression in the normal and neoplastic mast cells.

Matriptase, a type II transmembrane serine protease, is distributed in almost all normal human epithelium. Several studies have demonstrated that matriptase expression is correlated with tumor progression in epithelium-derived cancer cells. Mast cells, which originate from pluripotent hematopoietic cells in the bone marrow, can produce and store almost cellular-specific neutral serine proteases, such as tryptase and chymase, and are functionally involved in both the immediate hypersensitivity response and anaphylactic shock. Mast cells are significantly increased in several neoplasms, indicating that they most likely play a role in degrading the tissue matrix. Recently, trypsin has been revealed to activate the latent matriptase on the surface of several human cancer cell lines, suggesting that matriptase and trypsin cooperatively function in extracellular proteolysis. In our study, almost all mast cells in tissues throughout the body stained positive for matripase. Matripase was also found in neoplastic mast cells. To our knowledge, this is the first time that matriptase has been shown to be expressed by mast cells. Therefore, we suggest that this expression of matriptase may not only be useful as an additional marker for mast cells but also be involved in their physiopathological function.

Association of cortactin and fascin-1 expression in gastric adenocarcinoma: correlation with clinicopathological parameters.

Cortactin and fascin-1 are important factors in tumor progression. We tested the hypothesis that cortactin and fascin-1 expression correlates with clinicopathological parameters of gastric adenocarcinoma. Immunohistochemical analysis of cortactin and fascin-1 was done using tissue microarrays of 100 surgical specimens, including 20 well-differentiated, 20 moderately differentiated, and 60 poorly differentiated gastric adenocarcinomas. Among the 20 well-differentiated gastric adenocarcinomas, 15 cases (75%) showed negative or weak staining (1+); 5 cases (25%) had moderate (2+) or strong (3+) cortactin expression. Among the 60 poorly differentiated gastric adenocarcinomas, more than three-quarters of the cases (76.7%) had moderate or strong cortactin expression; 14 cases (23.3%) had weak staining. Of 20 well-differentiated gastric adenocarcinoma cases, 14 (70%) showed negative or weak staining of fascin-1, whereas nearly one-third (30%) had moderate or strong expression. Among the 60 poorly differentiated gastric adenocarcinomas, 32 (53.3%) exhibited moderate or strong fascin-1 expression; fewer than half of the cases showed negative or weak staining. Higher intensity of cortactin and fascin-1 staining correlated directly with more-advanced cancer stages (TNM) and inversely with survival rates. Our findings suggest the possibility that pharmacological inhibitors of cortactin and fascin-1 activity may slow down tumor progression and prolong survival time in patients with gastric adenocarcinomas.

Overexpression of fascin-1 in advanced colorectal adenocarcinoma: tissue microarray analysis of immunostaining scores with clinicopathological parameters.

OBJECTIVE: Fascin-1 is an actin-binding protein that promotes cell proliferation, adhesion and motility. We tested the hypothesis that fascin-1 expression correlates with clinicopathological parameters of colorectal adenocarcinomas. METHODS: Immunohistochemical analysis of fascin-1 was performed in tissue microarrays of 91 surgical specimens, including 32 well, 33 moderately, and 26 poorly differentiated colorectal adenocarcinomas; and in 22 specimens from colorectal adenomas with dysplasia. RESULTS: Scattered fascin-1 expression was demonstrated in 9 control specimens of normal colonic glandular epithelia. Higher fascin-1 immunostaining scores were significantly associated with advanced dysplasia in colorectal adenomas (mild 4.2 +/- 1.3, moderate 13.5 +/- 5.3, and severe 22.5 +/- 6.7) and high-grade histopathological differentiation of colorectal adenocarcinomas (grade I 88.6 +/- 9, grade II 101 +/- 11, and grade III 144 +/- 13). Higher immunostaining scores of fascin-1 were also significantly associated with advanced T stage (T1: 42 +/- 10, T2: 60 +/- 12, T3: 108 +/- 12, and T4: 142 +/- 15). Higher fascin-1 scores were related with more advanced M and N stages of colorectal carcinomas, but not significant correlation. CONCLUSIONS: Higher expression of fascin-1 correlates significantly with tumor grades and TNM stages in colorectal adenocarcinomas and also with levels of dysplastic change in colorectal adenomas.

STI571 sensitizes nasopharyngeal carcinoma cells to cisplatin: sustained activation of ERK with improved growth inhibition.

Previously, we demonstrated that c-kit and stem cell factors (SCF) commonly co-expressed in primary and metastatic nasopharyngeal carcinomas (NPC), and in HONE-1 NPC cells with tyrosine autophosphorylation of c-kit. These findings suggest that the SCF/c-kit signaling may contribute to pathogenesis of NPC. Therefore, the efficacy of STI571 treatment alone and when combined with cisplatin on HONE-1 cells were evaluated. STI571 induced growth inhibition at the IC50 concentration (14.9 microM). When the concentration was at or higher than 30 microM, the induction of cell apoptosis was observed. The effects of STI571 were shown to be mediated by the sustained activation of ERK but did not involve the inhibition of c-kit signal activity. When the STI571 (5 microM) and cisplatin (5 microg/ml) treatments were combined, there were further inductions of ERK activation resulting in obviously enhanced growth inhibition and induction of cell apoptosis. In a xenograft model, STI571 (50 mg/kg/day) showed only a limited ability to inhibit HONE-1 cell growth, but when combined with cisplatin (3 mg/kg/twice a week) treatment, there was a significant improvement in growth inhibition compared with STI571 or cisplatin treatment alone. Our results provide experimental support for the advanced NPC therapeutic trials using the combined STI571 and cisplatin treatment.

Association of EMMPRIN and fascin expression in renal cell carcinoma: correlation with clinicopathological parameters.

EMMPRIN and fascin are important factors in tumor invasion and progression. We tested the hypothesis that expression of EMMPRIN and fascin correlate with clinicopathological parameters of renal cell carcinoma (RCC). Immunohistochemical analysis of EMMPRIN and fascin were performed in tissue microarrays of 100 surgical specimens, including 35 clear-cell RCC (CRCC), 21 clear-cell RCC with granular differentiation (GRCC), 12 chromophobe RCC (ChRCC), 8 papillary RCC (PRCC), 9 carcinoma of the collecting duct of Bellini (CDC), 10 clear-cell RCC with sarcomatoid differentiation (SRCC), and 6 metastatic RCC. Average immunoscores of EMMPRIN were 100.8 in CRCC, 195.2 in GRCC, 298.4 in ChRCC, 219.2 in PRCC, 186.1 in CDC, 226.9 in SRCC, and 151.7 in metastatic RCC. Among all included cases, average EMMPRIN immunoscores were 84.6 in grade I, 130.4 in grade II, 184.3 in grade III, and 223.5 in grade IV. Additionally, average immunostaining scores of fascin were 53.6 in CRCC, 289.3 in GRCC, 193.3 in ChRCC, 151.8 in PRCC, 181.3 in CDC, 275.4 in SRCC, and 131.7 in metastatic RCC. Average fascin immunoscores were 59.3 in grade I, 91.6 in grade II, 130.2 in grade III, and 194.7 in grade IV. Higher EMMPRIN and fascin immunoscores also correlated significantly with TNM stages and survival rates in RCC. Significant correlation was found between EMMPRIN and fascin expression. In conclusion, higher expression of EMMPRIN and fascin correlate significantly with histological grades, clinical stages, and survival rates of RCC.

Decreased matriptase/HAI-1 ratio in advanced colorectal adenocarcinoma of Chinese patients.

Matriptase is a serine protease expressed by tumors of surface epithelial origin. We tested the expressions of matriptase and hepatocyte growth factor activator inhibitor-1 (HAI-1) maybe associated with the progression of colorectal adenocarcinoma. Immunohistochemical analysis of matriptase and HAI-1 was performed in tissue microarray slides of 91 colorectal adenocarcinomas with various degrees. The matriptase scores in moderately (346.7 +/- 10.6) and poorly differentiated (248.1 +/- 12.9) were significantly lower than those in well differentiated (368.4 +/- 9.6) colorectal adenocarcinomas. The matriptase/HAI-1 ratios in poorly (1.8 +/- 0.4) and moderately differentiated (1.8 +/- 0.3) were significantly lower than in well differentiated (2.2 +/- 0.2) colorectal adenocarcinomas. Otherwise, the matriptase scores and matriptase/HAI-1 ratio showed significant reverse correlation with more advanced TNM stages of colorectal adenocarcinomas in Chinese patients. In conclusion, pharmacological inhibitors of matriptase may not be effective treatment for advanced colorectal adenocarcinomas.

Increasing expression of extracellular matrix metalloprotease inducer in renal cell carcinoma: tissue microarray analysis of immunostaining score with clinicopathological parameters.

AIM: Renal tumor cell invasion is responsible for both local tissue destruction and distant metastasis. Invasion is largely mediated by matrix metalloproteases that are thought to be induced by tumor cell-derived extracellular matrix metalloprotease inducer (EMMPRIN) in surrounding fibroblasts. We hypothesized that EMMPRIN and matrix metalloproteinase-9 (MMP-9) are over-expressed in renal cell carcinoma. METHODS: Immunohistochemical analysis of EMMPRIN and MMP-9 was performed in tissue microarrays of 79 renal cell carcinomas including 12 cases of chromophobe renal cell carcinoma (ChRCC), 53 cases of clear cell renal cell carcinoma (CRCC), 8 cases of papillary renal cell carcinoma (PRCC), and 6 cases of carcinoma of the collecting ducts of Bellini (CoRCC). RESULTS: All renal cell carcinomas showed significant immunohistochemical expression of EMMPRIN. The EMMPRIN score in ChRCC (321+/-21) was significantly higher than in other histological subtypes of RCC (166+/-19 for CRCC; 276+/-24 for PRCC; 98+/-17 for CoRCC). MMP-9 was mainly expressed in tumor stromal cells and not in non-cancerous fibrovascular regions. The percent positive staining of MMP-9 at the invasive front of tumor cells was significantly higher in CRCC than in ChRCC, PRCC, or CoRCC. Higher EMMPRIN scores in CRCC were associated with shorter survival time, and correlated with higher T staging and nuclear grading. CONCLUSIONS: Our findings demonstrate for the first time that EMMPRIN is over-expressed in renal cell carcinomas. Increased expression of EMMPRIN in tumor cells is associated with poor prognosis of patients with CRCC.