[Show abstract][Hide abstract] ABSTRACT: Introduction
Patients with muscle-invasive bladder cancer (MIBC) often undergo various preoperative treatments to improve survival; however, their efficacy and safety remain unclear.
Materials and methods
The anti-tumour effects and adverse events were evaluated in 163 MIBC patients who received systemic chemotherapy (SC, n = 34), intra-arterial chemotherapy (IAC, n = 50), or combined IAC and radiotherapy (IAC+R, n = 79).
Pathological complete responses were observed in 17.6%, 22.0%, and 43.0% of patients in the SC, IAC, and IAC+R groups, respectively, with respective 5-year overall survival rates of 42.0%, 46.7%, and 50.3%. Multivariate analysis showed that successful IAC+R protocol administration was a significant predictor for survival (hazard ratio = 0.16, p = 0.028). The incidence of severe adverse events was higher in the IAC+R group (36.7%) than in the SC (9.8%) and IAC groups (16.0%).
IAC+R was useful for patients with MIBC. Successful completion and optimal patient selection were important for this treatment strategy.
European Journal of Surgical Oncology (EJSO). 09/2014;
[Show abstract][Hide abstract] ABSTRACT: Cardiac metastasis of renal cell carcinoma is an exceptional event, particularly when there is lack of inferior vena cava involvement. Indeed, only a few cases have been reported worldwide thus far. Moreover, discussion of treatment and follow-up strategies for cardiac metastasis of renal cell carcinoma is important because of the high risk of sudden death.
[Show abstract][Hide abstract] ABSTRACT: Key Clinical MessagePelvic organ prolapse (POP) is common among multiparous elderly women. POP related to obstructive anuria is very uncommon, but can be life-threatening if untreated. In this report, the patient survived from a septic shock with multidisciplinary treatment and was completely cured of POP after tension-free vaginal mesh repair.
[Show abstract][Hide abstract] ABSTRACT: Twist has been reported to play crucial roles for malignant aggressiveness; however, detailed pathological significance of Twist in renal cell carcinoma (RCC) is not fully understood. The present study was to clarify clinical significance and molecular functions of Twist in patients with RCC.
International journal of clinical and experimental pathology. 01/2014; 7(6):3158-65.
[Show abstract][Hide abstract] ABSTRACT: Angiogenesis plays an important role in cancer progression in many types of cancer. Evaluation of angiogenesis is often performed, but the optimal methodology for human cancer has not been agreed upon. As adequate evaluation of angiogenesis in cancer tissues might be important for prediction of prognosis and treatment decisions, we evaluated angiogenesis semiquantitatively by assessing microvessel density (MVD) in urothelial cancer of the upper urinary tract (UC-UUT). We compared the performance of three endothelial cell markers (CD31, CD34, and CD105) on formalin-fixed tissues from 122 patients diagnosed with UC-UUT without metastasis. Vascular endothelial growth factor (VEGF)-A expression was also evaluated immunohistochemically. Correlations between MVD with each marker and pT stage, grade, survival, and VEGF-A expression were investigated. Mean (standard deviation) MVD as estimated by immunohistochemical staining with anti-CD31, anti-CD34, and anti-CD105 were 47.1 (17.9)/high-power field (HPF), 70.9 (19.5)/HPF, and 31.2 (16.7)/HPF, respectively. Although all MVDs were significantly associated with pT stage and grade, CD105-MVD showed the strongest association. Similarly, CD105-MVD showed the strongest correlation with VEGF-A expression (r = 0.530, p < 0.001). Although all MVDs were associated with metastasis-free survival and cause-specific survival on univariate analysis, only CD105-MVD was retained as an independent predictor in multivariate analysis including pT stage and grade. CD105-MVD may be the preferred marker for semiquantitative assessment of angiogenesis in patients with UC-UUT.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 08/2013; · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human antigen R (HuR) regulates the stability of mRNA and is associated with cell proliferation, angiogenesis, and lymphangiogenesis. However, the clinical significance and pathological role of HuR in bladder cancer remains unclear. The main objective of this investigation was to clarify the relationships between HuR expression and clinical significance and cancer cell proliferation, angiogenesis, lymphangiogenesis, and expressions of cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF)-A, -C, and -D.
All expressions were examined by immunohistochemical techniques in 122 formalin-fixed specimens of bladder cancer patients. HuR expression was evaluated separately with cytoplasmic and nuclear staining. Cell proliferation, angiogenesis and lymphangiogenesis were measured as the percentage of Ki-67-positive cell (proliferation index, PI), CD34-stained vessels (microvessel density, MVD), and D2-40-stained vessels (lymph vessel density, LVD). Relationships between each HuR expression and clinicopathological features, prognosis, and expressions of COX-2 and VEGFs were analyzed by multi-variate analyses. HuR expression was also investigated in 10 mice of N-Butyl-N-[4-hydroxybutil] nitrosamine (BBN) induced bladder cancer model.
In human tissues, high cytoplasmic expression was seen in 5% and 25.4% of normal and cancer cells, respectively. Nuclear HuR expression bore no significant relationship to any pathological features. However, cytoplasmic HuR expression appeared positively associated with pT stage and grade (P<0.001). In mouse tissues, similar trends were confirmed. Cytoplasmic expression correlated with PI, MVD, and LVD, as well as expression of VEGF-A and -C, but not VEGF-D. High cytoplasmic expression of HuR was a significant predictor of metastasis and cause-specific survival, and was identified as a prognostic correlative factor for metastasis (hazard ratio, 4.75; P = 0.028) in a multivariate analysis model that included pathological features.
Cytoplasmic HuR appears to play important roles in cell proliferation, progression, and survival of bladder cancer patients. Its expression was associated with angiogenesis, lymphangiogenesis, and expressions of VEGF-A and -C.
PLoS ONE 03/2013; 8(3):e59095. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The biological activities of prostaglandin E2 are mediated through their specific receptors, E prostanoid receptors (EPRs). This family comprises 4 subtypes (EP1R-4R), and has been associated with cancer development and progression. In urological cancers, expression of EP2R and EP4R can be significant predictors of survival for renal cell carcinoma (RCC). On the other hand, EP1R, EP2R, and EP4R are known to be associated with carcinogenesis and malignant aggressiveness in prostate cancer. In addition, EP4R has been associated with tumor progression and prognosis in urothelial cancer of the upper urinary tract. There is a general agreement that non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of several malignancies including colorectal cancer. However, NSAIDs often cause gastrointestinal injury and nephropathy. On the other hand, cyclooxygenase (COX)-2-selective inhibitors can reduce the progression of cancer via the suppression of cell proliferation angiogenesis without decreasing adverse reactions. However, COX-2-selective inhibitors might increase the risk of cardiovascular disease, including myocardial infarction. More selective and detailed control of COX-2-mediated signals is thus needed to improve anti-tumor effects and to decrease adverse reactions. EPRs are expected to serve as new therapeutic targets in urological cancer, because they are more selective in malignant phenotypes. Finally, we speculate that some EPRs inhibitors may reduce adverse events and exert more intense effects on urological cancer.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To clarify the detailed pathologic roles of prostaglandin E(2) in prostate cancer tissues, the present study investigated the clinical significance and prognostic roles of the density of tumor-associated stromal cells expressing specific receptors for prostaglandin E(2), termed "E-prostanoid (EP)1-4 receptors (EP1R-4Rs)." METHODS: The expression of each receptor was immunohistochemically examined in 114 formalin-fixed biopsy specimens. Correlations with clinicopathologic features were investigated in these specimens. Angiogenesis and lymphangiogenesis were measured by the percentage of CD34-stained vessels (microvessel density) and D2-40-stained vessels (lymph vessel density). The relationships between the density of each EPR-stained cells and the microvessel density or lymph vessel density were evaluated in 62 prostate cancer tissues obtained by radical surgery for more detailed analysis in a wider area of prostate cancer tissue. RESULTS: The density of tumor-associated cells with EP2R expression was positively associated with the N (P < .001) and M (P = .002) stages. Similarly, EP3R-positive stromal cell density was significantly associated with the N (P = .033) and M (P = .026) stages. The density of EP2R- and EP3R-stained cells correlated with the microvessel density (r = 0.42, P < .001) and lymph vessel density (r = 0.36, P = .012), respectively. A greater density of EP2R-stained cells was recognized as an independent predictor of progression (hazard ratio 7.26, P = .002) on multivariate analysis. CONCLUSION: EP2R- and EP3R-stained cells might play important roles in tumor progression, angiogenesis, and lymphangiogenesis in prostate cancer. The density of EP2R-stained stromal cells could offer a useful predictor of biochemical recurrence after radical surgery.
[Show abstract][Hide abstract] ABSTRACT: The prognosis of patients with advanced and recurrent urothelial cancer (UC) is poor. Although cisplatin (CDDP)-containing chemotherapy is the most effective regimen in these patients, there is no other established chemotherapeutic regimen. We administered combination therapy with low-dose gemcitabine (GEM) and paclitaxel (PTX), named low-dose gemcitabine-paclitaxel (LD-GP) therapy, as salvage therapy for these patients. The aim was to evaluate the anti-tumoral effects, relief of pain, and toxicity of LD-GP therapy in patients with resistance to CDDP-containing therapy.
Thirty-five patients with advanced UC, previously treated with CDDP-containing regimens, were treated with LD-GP therapy (GEM, 700 mg/m(2) + PTX, 70 mg/m(2) on day 1 and 8, repeated every 28 days). Pain was measured on a visual analog scale before and after treatment. Pain relief and survival were compared between this and other treatment regimens.
None of the patients had complete response to LD-GP therapy. Partial response and stable disease were seen in 25.7 and 62.9 % of patients, respectively. Kaplan-Meier curves showed better survival in patients with LD-GP therapy than with others (p = 0.034). Twenty-eight patients (80.0 %) had adequate pain relief, and only two patients needed to increase their analgesics. Other regimens demonstrated pain relief in 30.4 % of patients. Common toxicities included leukopenia, with five patients requiring granular colony-stimulating factor therapy (14.3 %). The most common non-hematologic toxicity was fatigue (n = 7, 17.1 %).
LD-GP therapy is feasible and well tolerated as salvage therapy in patients with advanced UC with resistance to CDDP-containing therapy.
Cancer Chemotherapy and Pharmacology 08/2012; 70(3):451-9. · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Squamous cell carcinoma (SCC) of the bladder is a relatively rare malignancy and the standard treatment is surgical resection. Prognosis of unresectable and recurrent SCC of the bladder is poor because no effective treatment is available at present. Here, we describe the response of one patient with this cancer to combination chemotherapy of gemcitabine and paclitaxel. A 47-year-old man with recurrent bladder SCC underwent radical cystectomy, but initially refused any adjuvant therapy. The pathological diagnosis was pT3. The patient was treated with three cycles of methotrexate, vinblastin, epirubicin, and cisplatin but with no response (no decrease in tumor volume). Subsequently, he received the combination chemotherapy of gemcitabine (GEM, 700 mg/m(2) on days 1 and 8) and paclitaxel (PTX, 700 mg/m(2) on days 1 and 8) per each 28-day cycle. After five cycles, the tumor volume had decreased from 562 to 101 cm(3) (18.0%). The combination therapy was reduced to GEM monotherapy, but the tumor volume increased to 573 cm(3). GEM+PTX administration was re-instituted; however, the patient died 21 months after recurrence. The combination GEM+PTX chemotherapy was applied at the outpatient treatment and caused no severe side-effects. Although the maintenance chemotherapy of GEM+PTX did not induce complete remission, it improved quality of life and had no serious side-effects, making it a promising combination chemotherapy for recurrent SCC of the bladder. Although further studies are necessary to determine its therapeutic efficacy, we suggest that this combined therapy is a useful option in the treatment of this disease including recurrent cases.
Anticancer research 12/2011; 31(12):4465-8. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To clarify the clinical and prognostic significance of cortactin and phosphorylated cortactin in patients with sarcomatoid renal cell carcinoma (SRCC).
We retrospectively reviewed the data from 31 patients with SRCC and 33 with conventional renal cell carcinoma matched for clinicopathologic features. The immunoreactive score for cortactin, pY421 cortactin, and pY466 cortactin were measured using immunohistochemistry. The relationships between each immunoreactive score and the clinicopathologic features and survival were investigated.
The immunoreactive score of p421 cortactin, but not that of cortactin and pY466 cortactin, was significantly greater in SRCC than in conventional renal cell carcinoma (P < .001). The expression of pY421 cortactin in SRCC correlated with the pT stage and metastasis (P < .001). The expression of pY466 cortactin showed a similar trend with pT stage (P = .043) but not with metastasis. Although both of pY421 cortactin and pY466 cortactin were identified as useful predictors for survival in univariate analyses, only pY421 cortactin expression was considered an independent predictor in patients with SRCC (odds ratio 4.53, 95% confidence interval 1.07-19.12, P = .040) in the multivariate analysis model, including pT stage and metastasis.
Our results have demonstrated that phosphorylation of cortactin is a key process in malignant aggressiveness, and its expression is a useful predictor of cause-specific survival and could be a useful potential therapeutic target in patients with SRCC.
[Show abstract][Hide abstract] ABSTRACT: Urachal cancer is a rare malignancy and the standard treatment is surgical resection. The prognosis of recurrent and metastatic urachal cancer is extremely poor because there is no established chemotherapy regimen. Here, the response of one patient with recurrent urachal cancer to combination chemotherapy of gemcitabine (GEM) and cisplatin (CDDP) (GC) is described. And the chemo- and radiotherapeutic regimens available for such patients are reviewed. A 67-year-old man diagnosed with stage IIIA urachal cancer underwent complete surgical resection. However, pelvic recurrence was detected on computed tomography (CT) 5 months after surgery. GC therapy was started immediately and resulted in a pronounced reduction in pelvic mass after three cycles. However, a follow-up CT scan taken 5 months later showed growth of the pelvic mass and new liver metastasis. He received GC therapy again, which resulted in reduction of the pelvic and liver metastatic masses after two cycles. However, the patient refused another course of GC therapy due to severe side-effects. Subsequent progression of the disease included spread in both regions, followed by death 16 months after recurrence. Various treatment strategies offer relatively long survival of patients with urachal cancer including those with recurrence and metastasis. Although further studies are necessary to determine its therapeutic efficacy, GC therapy may be a useful option in the treatment of urachal tumors, including recurrent tumours.
Anticancer research 06/2011; 31(6):2335-8. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The clinical significance of prostaglandin E2 receptor (EPR) expression in renal cell carcinoma (RCC) tissues remains unclear. Patients and Μethods: Four subtypes of EPRs were examined in 112 human RCC tissues by immunohistochemical and Western blot analysis. The relationships between EPR immunoreactivity score (IS) and various pathological features and survival were then analyzed.
The IS of EP4R was significantly higher (p < 0.001) in cancer cells (mean = 2.7 and SD = 2.1) than in normal kidney tissues (1.8 and 1.2). EP4R expression correlated with pT stage, metastasis, and grade. EP2R expression was also associated with metastasis. Expressions of both EP2R and EP4R were found to be significant predictors for cause-specific survival on Kaplan-Meier survival analysis (p = 0.006 and 0.023, respectively).
EP2R and EP4R may play important roles in malignant behavior. EP4R in particular was closely associated with pathological features, implicating this receptor as a potential therapeutic target in patients with RCC.
Anticancer research 02/2011; 31(2):597-605. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Androgen insensitivity syndrome, gonadectomy, estrogen supplementation a 23-year-old single female visited our gynecological clinic because of primary amenorrhea. The patient's breast development was good. However the patient had thin pubic hair and blind-ending vagina. Serum levels of estrogen E2, testosterone, luteinizing hormone (LH) and follide stimulating hormone (FSH) were 37.0, 497 pg/ml, 22.0 and 8.7 mIU/ml, respectively. Chromosomal analysis was a karyotype of 46, XY. There was no uterus and no ovaries. However, there were bilateral inguinal elastic masses which were gonads. The patient was diagnosed with complete androgen insensitivity syndrome and bilateral gonadectomy was performed. The postoperative course was good and the patient is receiving estrogen replacement therapy.
[Show abstract][Hide abstract] ABSTRACT: The expression of matrix metalloproteinase-7 (MMP-7) correlates with the malignant potential of various tumors and patient survival. We investigated the clinical and prognostic significance of MMP-7 expression in cancer cells and endothelial cells in human renal cell carcinoma (RCC).
We reviewed tissue samples of 156 patients with RCC who had undergone radical operation. MMP-7 expression was examined by immunohistochemistry. Sections containing MMP-7-positive vessels were also stained for CD34. The density of MMP-7-positive vessels was determined by a computer-aided image analysis system. Multivariate analysis was done to assess relevant variables for invasion, metastasis, and cause-specific survival.
The proportion of MMP-7-expressing tumor cells were significantly higher (P < 0.001) than that of normal cells. MMP-7-positive vessels were considered blood vessels based on staining for CD34, and their density was increased in tumor areas. The proportion of MMP-7-expressing cancer cells and density of MMP-7-positive vessels correlated with grade, pathologic tumor stage, and metastasis. Multivariate analysis showed that MMP-7 expression on cancer cells correlated with pathologic tumor stage only, whereas MMP-7-positive vessel density correlated with metastasis only. The elevated status of MMP-7 in cancer tissues was an independent predictor for cause-specific survival (odds ratio, 8.61; P = 0.040) by multivariate analysis.
Our results showed that MMP-7 influences tumor progression by regulating invasion and angiogenesis. Multivariate analysis showed that MMP-7 status of cancer tissues was strong predictor of poor prognosis. Our results suggest that MMP-7 targeting treatment may be a potential target against RCC.
Clinical Cancer Research 01/2007; 12(23):6998-7003. · 7.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lymph node metastasis is an important prognostic factor in many types of cancer. Recently several specific markers for lymphatic endothelium were developed that facilitate the quantification of lymphangiogenesis in human cancer tissues. We investigated the clinical and prognostic significance of lymphangiogenesis in patients with transitional cell carcinoma of the upper urinary tract.
We measured lymph vessel density and relative lymphatic vascular area in 125 specimens by quantitative immunohistochemical staining for D2-40 antibody (DakoCytomation, Glostrup, Denmark). These parameters were examined in the intratumor and peritumor areas, and measured using image analysis software.
Peritumor lymph vessel density and peritumor lymphatic vascular area correlated with lymph node metastasis and tumor grade. In the intratumor area lymphatic vessels were detected in only 16.0% of specimens. However, the presence of intratumor lymphatic vessels was associated with lymph node metastasis (p = 0.002). Multivariate analysis identified high peritumor lymphatic vascular area and the presence of intratumor lymphatic vessels as significant and independent factors of metastasis-free survival after surgery (OR = 5.11, p = 0.020 and OR = 2.92, p = 0.025, respectively). Multivariate analysis also identified the presence of intratumor lymphatic vessels as the only independent predictive factor of cause specific survival (OR = 3.89, p = 0.049).
Lymphangiogenesis may have important roles in tumor metastasis and survival in patients with transitional cell carcinoma of the upper urinary tract. Quantification of lymphatic vessels, especially peritumor lymphatic vascular area and intratumor lymphatic vessels, was useful for predicting metastasis-free survival. In addition, the presence of intratumor lymphatic vessels was an independent predictor of cause specific survival.
The Journal of Urology 08/2006; 176(1):348-53. · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prostaglandin E2 receptor, EP4 receptor (EP4R), plays an important role in the development of transitional cell carcinoma of the upper urinary tract (TCC-UUT). However, the clinical significance of other EP receptors (EP1R-3R) is not clear. Furthermore, the pathological function of EP receptors in such patients is not understood. In the present study, we examined the expression of EP1R-3R in 101 TCC-UUT tissues by immunohistochemistry. Furthermore, we defined the relationship between cyclooxygenase (COX)-2 and EP receptor expression, proliferation index (PI), microvessel density (MVD), and expression of metalloproteinase-2 (MMP-2), urokinase-type plasminogen activator (uPA), and exon v6 containing CD44 isoform (CD44 v6) by multivariate analysis. The expression of EP1R, EP2R, and EP3R was positive in 20 (19.8%), 26 (25.7%), and 14 (13.9%) tumor samples, respectively. Expression of these receptors was not associated with pathological findings or survival. COX-2 and EP4R were independently associated with MVD and MMP-2, and uPA or PI and MMP-2, respectively. Other EP receptors were not influenced by any factors. Our results suggest that EP1R-3R play a minimal role in cancer progression in patients with TCC-UUT. On the other hand, EP4R regulates tumor progression via cancer cell proliferation and MMP-2, distinct from COX-2.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 07/2006; 448(6):822-9. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lymph vessel density (LVD) and microvessel density (MVD) correlate with the malignant potential of tumors and patient survival. Vascular endothelial growth factors (VEGF)-A, VEGF-C, and VEGF-D could modulate LVD and MVD. We investigated the clinical and prognostic significance of LVD and MVD on lymphangiogenic and angiogenic function of VEGF-A, VEGF-C, and VEGF-D in human bladder cancer.
We reviewed tissue samples from patients with nonmetastatic bladder cancer who had undergone transurethral resections (n = 126). The densities of D2-40-positive vessels (LVD) and CD34-positive vessels (MVD) were measured by a computer-aided image analysis system. Expression of VEGF-A, VEGF-C, and VEGF-D was examined by immunohistochemistry; survival analyses and their independent roles were investigated using multivariate analysis models.
LVD was associated with tumor grade but not with pT stage. LVD was associated with metastasis-free survival (log rank P = 0.039), but was not an independent prognostic factor. Although MVD affected survival, the combination of high LVD and high MVD in tumors was an independent predictor of metastasis-free survival. Although VEGF-C expression was positively associated with both LVD and MVD, VEGF-D was associated only with LVD. VEGF-A expression was associated with MVD in univariate analysis, however, it was not an independent factor.
Lymphangiogenesis and angiogenesis influence metastasis-free survival, and are regulated by VEGF-C and/or VEGF-D. Our results suggest that LVD and MVD are useful tools for the selection of postoperative management and treatment strategies in patients with bladder cancer.
Clinical Cancer Research 03/2006; 12(3 Pt 1):800-6. · 7.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic allograft nephropathy (CAN), associated with late-allograft dysfunction is caused by alloantigen-dependent and -independent mechanisms, and eventually leads to interstitial fibrosis (ci). Activation of complement cascade is considered to be a poor prognostic marker of graft survival. This study was designed to examine the relationship between the expression of C4d and heat-shock protein 47 (HSP47, a collagen-specific chaperone) in the development of interstitial fibroproliferative lesions in CAN.
Sixty-three renal allograft biopsy specimens, obtained from 48 patients, were examined for the expression of C4d, HSP47, CD68 and alpha-smooth muscle actin (alpha-SMA) by immunohistochemistry. Double-staining was performed to determine the colocalization of C4d and HSP47. The relationship of between the expression of C4d, HSP47, CD68 and alpha-SMA and the clinical and histopathological parameters were statistically analysed.
No expression of C4d was noted in the tubulointerstitium including peritubular capillary (PTC) of the control kidney. C4d was expressed in PTC in one-third of allograft renal tissues with morphological evidences of CAN. The interstitial cells around the fibrotic areas of the PTC of CAN were positive for the expression of HSP47. The deposition of C4d in PTC correlated with interstitial expression of HSP47 around the PTC. Most HSP47 expressing cells were phenotypically altered myofibroblasts, as determined by the dual staining of alpha-SMA.
The increased expression of HSP47 positively correlated with the expression of C4d in PTC, and might contribute to the progression of interstitial ci in CAN.
[Show abstract][Hide abstract] ABSTRACT: Urokinase-type plasminogen activator (uPA) has an important role in tumor progression through the degradation of extracellular matrix. In addition, uPA receptor (uPAR) and plasminogen activator inhibitors (PAIs), composed of PAI-1 and 2, are also known to affect such activities. Tumor associated macrophage (TAM) is an important regulator of tumor progression that is associated with the uPA system in various cancers. However, to our knowledge the clinical significance of PAI-2 and the relationship between the uPA system and TAM in human renal cell carcinoma (RCC) tissues have not been investigated. We investigated and clarified these issues.
The subjects of the current study were 106 consecutive surgically resected specimens from patients with RCC. The expression of uPA, uPAR, PAI-1 and PAI-2 was determined by immunohistochemistry. We also examined the relationships among these molecules, survival and TAM.
The mean immunoreactive scores (range 0 to 6) of uPA, uPAR, PAI-1 and PAI-2 were 3.09, 2.22, 1.99 and 0.56, respectively. These scores correlated with the grade and presence of metastasis. The expression of uPA, uPAR and PAI-1 but not PAI-2 correlated negatively with cause specific survival. Of uPA family members multivariate analysis showed that PAI-1 independently influenced cause specific survival. TAM counts correlated with PAI-1 only (p <0.001).
Our results suggest that PAI-1 is an important regulator of tumor progression and survival, and PAI-1 may modulate them via TAM. On the other hand, PAI-2 has a minimum role in survival. Our results may help discussions of treatment strategy in patients with RCC.
The Journal of Urology 09/2005; 174(2):461-5. · 3.75 Impact Factor