Biomedical subjects

Caj Haglund

Publications and source records attributed to Caj Haglund.

At least 37 records · Page 2Linked to original sources

PubMed2005

Cytoplasmic HuR expression is a prognostic factor in invasive ductal breast carcinoma.

HuR is a ubiquitously expressed mRNA-binding protein. Intracellular localization of HuR is predominantly nuclear, but it shuttles between the nucleus and the cytoplasm. In the cytoplasm it can stabilize certain transcripts. Because nucleocytoplasmic translocation of HuR is necessary for its activity, it was hypothesized that cytoplasmic HuR expression in cancer cells could be a prognostic marker. To test the significance of HuR in carcinogenesis of the breast, we have investigated HuR expression in a mouse mammary gland tumor model and from 133 invasive ductal breast carcinoma specimens. HuR expression was elevated in the cyclooxygenase-2 transgene-induced mouse mammary tumors, and its expression was predominantly cytoplasmic in the tumor cells. In the human carcinoma samples, high cytoplasmic immunoreactivity for HuR was found in 29% (38 of 133) of the cases. Cytoplasmic HuR expression associated with high grade (P = 0.0050) and tumor size over 2 cm (P = 0.0082). Five-year distant disease-free survival rate was 42% [95% confidence interval (95% CI), 26-58] in cytoplasm-high category and 84% (95% CI, 76-91) in cytoplasm-negative or -low category (P < 0.0001), and high cytoplasmic expression of HuR was an independent prognostic factor in a Cox multivariate model (relative risk 2.07; 95% CI, 1.05-4.07). Moreover, high cytoplasmic HuR immunopositivity was significantly associated with poor outcome in the subgroup of node-negative breast cancer in a univariate analysis (P < 0.0007). Our results show that high cytoplasmic HuR expression is associated with a poor histologic differentiation, large tumor size, and poor survival in ductal breast carcinoma. Thus, HuR is the first mRNA stability protein of which expression associates with poor outcome in breast cancer.

Animals↗

PubMed2005

Immunohistochemical expression of Bcl-2, Ki-67, and p21 in patients with papillary thyroid cancer.

Papillary thyroid cancer (PTC) is a slow-growing tumor with a favorable outcome. Still, some low-risk patients develop local or distant metastases and eventually die from their disease. Many molecular markers are involved in proliferation and apoptosis, including Bcl-2, Ki-67, and p21. Because age over 45 is the most important determinant of a poor survival, we analyzed whether the expression of these tumor proliferation markers differs between young and older PTC patients. Our study comprised 108 PTC patients retrospectively selected by age, i.e. those younger than 35 or older than 55 at diagnosis. Formalin-fixed, paraffin-embedded archival tissue blocks were analyzed for Bcl-2, Ki-67, and p21 protein expression by immunohistochemistry. We showed that expression of Ki-67 increases significantly with age, indicating that tumors in older patients may grow faster. This higher proliferative activity may explain the worse prognosis in these patients. Expression of p21 was higher in large tumors and in tumors extending beyond the thyroid capsule. Expression of Bcl-2 did not correlate with clinical parameters.

Adult↗

PubMed2005

Helicobacter pylori infection and low serum pepsinogen I level as risk factors for gastric carcinoma.

AIM: To study whether examination of CagA antibodies could increase the odds ratio for gastric cancer in a case-control study, and how often other serum markers of gastric cancer risk could be found in Helicobacter pylori -negative patients. METHODS: H pylori CagA and parietal cell antibodies (PCAs), and serum pepsinogen I (SPGI) levels were compared between patients with gastric cancer and controls who received endoscopic examination due to reasons other than gastrointestinal malignancy. RESULTS: The odds ratio (OR) for gastric cancer was 2.9 (95% CI 1.4-5.8) in H pylori + patients, and 2.4 (95% CI 1.2-4.9) in CagA+ patients. When results of H pylori and CagA antibodies were combined, OR increased to 5.0 (95% CI 2.5-10.0). Furthermore, if cardia cancer patients were excluded, the OR increased to 6.8 (95% CI 3.1-14.8). Among patients with a low SPGI level, the OR was 12.0 (95% CI 4.1-35.3). However, the risk was significant only in the older age group. The number of patients with low SPGI was significantly higher in H pylori -/CagA+ patients as compared to other cancer patients. CONCLUSION: Examination of both H pylori and CagA antibodies increases the OR for gastric cancer in our case-control study. CagA antibodies are important in detecting previous H pylori infection in advanced atrophic gastritis or cancer when spontaneous decline of H pylori antibodies occurs. SPGI may be helpful in screening elderly gastric cancer patients.

Adult↗

PubMed2005

Association of cyclooxygenase-2 and matrix metalloproteinase-2 expression in human breast cancer.

Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 (MMP-2) associates with reduced survival in human breast cancer. COX-2 may be directly involved with mammary carcinogenesis, since expression of COX-2 is sufficient for formation of breast tumors in transgenic mice, and COX-2 selective inhibitors can suppress tumorigenesis in rodent models of breast cancer. MMP-2 is an extracellular matrix degrading proteolytic enzyme that bas been linked to invasion and metastasis. A direct link between COX-2 and MMP-2 may exist, since inhibition of COX-2 activity can result in reduction of MMP-2 expression and activity. In this study we analyzed protein expression of COX-2 and MMP-2 in tissue array specimens of 278 invasive breast cancers by immunohistochemistry. Immunopositivity of these two markers was correlated with each other and with various clinicopathological parameters including survival. We found high COX-2 expression in 30% and high MMP-2 expression in 83% of the breast cancer specimens, and there was a positive association between the expression of these two factors (p = 0.003). It was especially evident that whenever COX-2 expression was high, MMP-2 expression was almost invariably high (95%). Furthermore, high expression of either COX-2 or MMP-2 associated with decreased disease specific survival when compared with the COX-2 or MPP-2 low group (p = 0.026 and p = 0.021, respectively). Taken together, our results indicate that expression of COX-2 protein is associated with expression of MMP-2 protein in human breast cancer and that both COX-2 and MMP-2 are markers of poor prognosis in breast cancer.

Biomarkers, Tumor↗

PubMed2005

Cytoplasmic HuR expression correlates with epithelial cancer cell but not with stromal cell cyclooxygenase-2 expression in mucinous ovarian carcinoma.

UNLABELLED: Cyclooxygenase-2 (COX-2) expression has been found to associate with poor prognosis in several types of carcinomas. HuR is an mRNA stability protein and it regulates the expression of COX-2. OBJECTIVES AND METHODS: We analyzed the expression of COX-2 and HuR in 64 mucinous ovarian carcinoma specimens by immunohistochemistry. RESULTS: In mucinous tumors, high COX-2 protein expression was found in epithelial cancer cells in 39% (22/56) and in stromal cells in 24% (13/55) of the specimens. The expression of COX-2 in cancer cells correlated with high grade (P = 0.0285), but stromal COX-2 expression had no correlation with any clinical parameter tested. Cytoplasmic HuR protein expression was observed in cancer cells in 47% (27/57) and in stromal cells in 7% (4/56) of the mucinous tumors, and it correlated with COX-2 expression in the cancer cells (P = 0.0162) but not in the stroma. CONCLUSION: Our results support the hypothesis that cytoplasmic HuR is connected to COX-2 expression in ovarian carcinoma, but that its role is restricted to the transformed epithelial cancer cells.

Adenocarcinoma, Mucinous↗

PubMed2005

Cyclooxygenase-2 expression in primary Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine skin tumor. The typical course of MCC is rapid progression of the primary tumor and metastatic dissemination to the regional lymph nodes. Thus far, no biological, prognostic marker has been established for this aggressive neoplasm. Cyclooxygenase-2 (Cox-2) is undetectable in most normal tissues, but it is induced in various cell types by inflammation and carcinogenesis. Although the expression and function of Cox-2 have been studied extensively in several carcinomas, little is known about Cox-2 expression in neuroendocrine carcinomas. The aim of the present report was to study Cox-2 expression in MCC and find out whether this expression correlates with outcome. METHODS: Immunohistochemical analysis for Cox-2 was performed on 22 primary MCC samples. RESULTS: Almost 70% of the samples showed positive staining. Protein expression of Cox-2 was sparse and low in intensity. We found a tendency for enhanced Cox-2 expression in tumors located in sun-exposed areas. Cox-2 expression had no significant statistical correlation with clinical parameters. CONCLUSIONS: MCC expresses Cox-2 in low levels, and the expression did not prove to be a prognostic factor. Furthermore, the low expression suggests that the primary treatment option for MCC is not therapeutic inhibition of Cox-2.

Aged↗

PubMed2004

Preoperative hCGbeta and CA 72-4 are prognostic factors in gastric cancer.

In gastric cancer, the role of tumour markers in assessment of prognosis is unconfirmed. In our study, we evaluated the prognostic significance of serum tumour markers carcinoembryonic antigen (CEA), CA 19-9, CA 72-4, CA 242 and free beta subunit of human chorionic gonadotropin (hCGbeta) in gastric cancer. Preoperative serum samples were obtained from 146 patients with gastric cancer, including 29 with stage I, 11 with stage II, 42 with stage III and 64 patients with stage IV cancer. Quantitation of CEA, CA 19-9, CA 72-4 and CA 242 in serum was performed with commercial assays. HCGbeta was measured with an in-house immunofluorometric assay based on monoclonal antibodies specific for the free beta-subunit of hCG. Survival analysis was performed with Kaplan-Meier life-tables and log-rank test, and with multivariate Cox regression analysis. Disease-specific cumulative 2-year survival rate was 40%. Serum levels of CEA, CA 72-4, CA 242 and hCGbeta showed significant correlation with stage (p<0.027); for CA 19-9 the association was of borderline significance (p=0.056). Of the studied markers, CA 19-9, CA 72-4, CA 242 and hCGbeta were found to be prognostic factors in univariate analysis (p< 0.022). In multivariate analysis, stage had the statistically most significant association with prognosis followed by hCGbeta, tumour histology according to the Laurén classification and by CA 72-4. In gastric cancer, tumour markers hCGbeta and CA 72-4 are independent prognostic factors in addition to stage and histological type of the tumour.

Adult↗

PubMed2004

Expression of trypsinogen-1, trypsinogen-2, and tumor-associated trypsin inhibitor in ovarian cancer: prognostic study on tissue and serum.

PURPOSE: The purpose is to study the prognostic significance of tissue expression of trypsinogen-1, trypsinogen-2, and tumor-associated trypsin inhibitor (TATI) and serum concentration of trypsinogen-2, trypsin-2-API (complex of trypsin-2 with alpha-1-proteinase inhibitor), and TATI in epithelial ovarian cancer. EXPERIMENTAL DESIGN: Expression of trypsinogen-1, trypsinogen-2, and TATI was determined by immunohistochemistry with monoclonal antibodies in tissue sections of tumors from 119 patients with untreated primary epithelial ovarian cancer. Preoperative serum concentrations of trypsinogen-2, trypsin-2-API and TATI were analyzed using specific immunoassays. RESULTS: Fifty-four percent of the tumors expressed trypsinogen-1, 45% expressed trypsinogen-2, and 30% expressed TATI. In patients with stage III and IV disease, TATI tissue expression (P = 0.002) and elevated TATI concentration in serum (P = 0.048) were associated with adverse cancer-specific and progression-free survival in univariate analysis. In multivariate analysis, TATI tissue expression (P = 0.005), tumor grade (P = 0.0001), histological type (P = 0.02), and stage (P = 0.0005) were independent prognostic factors for adverse cancer-specific survival and TATI tissue expression (P = 0.006) and grade (P = 0.0003) for progression-free survival. In multivariate analysis of all patients and those with advanced disease, serum trypsin-2-API concentration was an adverse prognostic factor for cancer-specific and progression-free survival, and it was independent of stage and histological type of the tumor (P <or= 0.01). CONCLUSIONS: Tissue expression of TATI and an elevated preoperative serum concentration of trypsin-2-API are strong independent prognostic factors in advanced epithelial ovarian cancer. These results suggest that trypsin expression plays a role in the progression of ovarian cancer. TATI and trypsin-2-API are of potential use as an aid for stratification of randomized studies and for selecting treatment strategies.

Adult↗

PubMed2004

Elevated cyclooxygenase-2 expression is associated with altered expression of p53 and SMAD4, amplification of HER-2/neu, and poor outcome in serous ovarian carcinoma.

PURPOSE AND EXPERIMENTAL DESIGN: Cyclooxygenase-2 (COX-2) is frequently expressed in human adenocarcinomas and inhibition of COX-2 suppresses tumor formation in various animal models of carcinogenesis. We analyzed expression of COX-2 protein in human serous ovarian carcinomas by immunohistochemistry (n = 442) and by Western blotting (n = 12) and COX-2 mRNA by reverse transcriptase PCR (n = 12). COX-2 immunoreactivity was correlated to clinicopathological variables and to expression of p53 and SMAD4 as detected by immunohistochemistry and to amplification of HER-2/neu as detected by in situ hybridization. RESULTS: COX-2 mRNA expression was detected in 75% (9 of 12) and COX-2 protein in 42% (5 of 12) of the serous ovarian adenocarcinoma specimens as detected by reverse transcriptase-PCR and Western blot analysis, respectively. Moderate to strong (elevated) immunoreactivity for COX-2 was detected in 70% (310 of 442) of the tumors. Elevated COX-2 expression associated with reduced disease-specific survival (P = 0.0011), high histological grade (P < 0.0001), residual tumor size > 1 cm (P = 0.0111), and age > 57 years (P = 0.0099). Tumors with altered immunostaining pattern for p53 or SMAD4 expressed more frequently elevated levels of COX-2 when compared with the tumors with normal staining pattern of these tumor suppressor genes (P < 0.0001 and P = 0.0004, respectively). In addition, elevated COX-2 expression associated with amplification of HER-2/neu oncogene (P = 0.0479). CONCLUSIONS: Our results suggest that elevated expression of COX-2 associates with reduced survival in serous ovarian carcinomas and that expression of COX-2 may be induced in these tumors by loss of tumor suppressor genes such as p53 and SMAD4 and by amplification of HER-2/neuoncogene.

Adolescent↗

PubMed2004

Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms). Part I-general overview.

The incidence of neuroendocrine tumours of the gastroenteropancreatic system seems to have increased during the past decade. New diagnostic and therapeutic procedures have aroused the interest of physicians, though most see very few cases of such diseases. A group of members of the Nordic Neuroendocrine Tumour Group decided to compile some guidelines to facilitate the diagnosis and treatment of patients with these tumours. Part I of these guidelines discusses the principles of histopathology, biochemical and radiological diagnosis as well as therapeutic options.

Antineoplastic Agents↗

PubMed2004

Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms). Part II-specific NE tumour types.

Part II of the guidelines contains a description of epidemiology, histopathology, clinical presentation, diagnostic procedure, treatment, and survival for each type of neuroendocrine tumour. We are not only including gastroenteropancreatic tumours but also bronchopulmonary and thymic neuroendocrine tumours. These guidelines essentially cover basic knowledge in the diagnosis and management of the different forms of neuroendocrine tumour. We have, however, tried to give more updated information about the epidemiology and histopathology, which is essential for the clinical management of these tumours.

Gastrointestinal Neoplasms↗

PubMed2004

Expression of cyclin A in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare and aggressive primary neuroendocrine carcinoma of the skin. Large tumours, in particular, show rapid progression and metastatic dissemination, while smaller tumours show less aggressive behaviour. Cyclin A is considered to play a central role in cell cycle control. Its overexpression has been found to correlate with prognosis in many types of carcinomas and sarcomas. Twenty-six MCC patients with complete clinical data were selected. Formalin-fixed paraffin-embedded primary tumour samples were immunohistochemically stained for cyclin A. Correlation between expression of cyclin A and primary tumour size, invasion of subcutaneous tissue, local recurrence, metastasis and survival was statistically analysed. Twenty-five samples expressed cyclin A, and the mean value of positive cells was 25%. Our findings demonstrate that even small and superficial MCC show overexpression of cyclin A. There was no statistical correlation between cyclin A expression and the above-mentioned variables. Cyclin A does not seem to be useful as a prognostic tool. Consequently, size of the primary tumour (>/=2 cm) remains the primary prognostic tool. As a result every tumour, even those small in size, should be considered aggressive and treated radically and rapidly.

Aged↗

PubMed2004

Malignancy in pheochromocytomas.

A catecholamine-secreting tumor arising from the chromaffin cells of the sympathoadrenal system was first termed pheochromocytoma by Poll in 1905. The term refers to the dysky (pheo) color (chromo) of the cut surface of the tumor when exposed to dichromate. Pheochromocytomas most commonly arise from the adrenal medulla. Extraadrenally located pheochromocytomas are called paragangliomas, and arise from the paraganglion system. An adrenal pheochromocytoma is usually a rounded, gray-white, firm tumor 3 to 5 cm in diameter. When larger, they can adhere to adjacent structures, although still not metastasizing. Most pheochromocytomas are benign. However, approximately 10% of these tumors metastasize. It is almost impossible to differentiate a benign from a malignant tumor only by histological criteria. Classically only metastasized tumors are considered malignant for certain. Many attempts have been made to find markers that would predict the future behavior of an unmetastasized pheochromocytoma. In this overview of malignancy in pheochromocytomas, different steps of the tumorigenesis and several markers associated with them are discussed.

Adrenal Gland Neoplasms↗

PubMed2004

Serum HCG beta and CA 72-4 are stronger prognostic factors than CEA, CA 19-9 and CA 242 in pancreatic cancer.

OBJECTIVE: In pancreatic cancer, the extent of the spread of the disease is considered to be the strongest prognostic factor. In addition, tumor markers, particularly CA 19-9, may also provide prognostic information. In this study, we evaluated the prognostic value of serum tumor markers CEA, CA 19-9, CA 242, CA 72-4 and hCG beta in pancreatic cancer. METHODS: Preoperative serum samples were obtained from 160 patients with pancreatic cancer, including 10 with stage I, 25 with stage II, 24 with stage III and 101 patients with stage IV cancer. Quantitation of CEA, CA 19-9, CA 242, and CA 72-4 in serum was performed with commercial assays. HCG beta was measured with an in-house immunofluorometric assay based on monoclonal antibodies specific for the free beta-subunit of hCG. Survival analysis was performed with univariate Kaplan-Meier life-tables and log-rank test, and with multivariate Cox regression analysis. RESULTS: Of the tumor markers studied, CA 19-9 was most frequently elevated. Overall 2-year survival was 10%. Stage, tumor location and size, curative resection, and CEA, CA 72-4 and hCG beta were all found to be prognostic factors (p < 0.026) in univariate analysis. In multivariate analysis, each marker had independent prognostic value (p < 0.011) when analyzed individually but adjusting for stage. When all the covariates were included in the same model, the strongest prognostic factor was hCG beta followed by CA 72-4 and stage. The other clinical characteristics and serum tumor markers contributed insignificant prognostic information. CONCLUSIONS: All the tumor markers studied (CEA, CA 19-9, CA 242, CA 72-4, and hCG beta) had prognostic value in pancreatic cancer, and hCG beta, CA 72-4, and stage were the strongest independent prognostic factors in this study.

Adult↗

PubMed2004

Estimating the probability of cancer with several tumor markers in patients with colorectal disease.

OBJECTIVE: The purpose of this study was to evaluate and compare serum tumor markers, carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4 and hCGbeta, and their value in the diagnosis of malignant colorectal disease. METHODS: The serum concentrations of the markers were measured in 204 patients with colorectal cancer and in 104 inpatients with benign colorectal disease. The combined use of the markers was evaluated with a logistic regression analysis. RESULTS: When all five markers were evaluated in the same model, only CEA and CA 72-4 provided significant diagnostic information (p < 0.001), indicating that their combination improves the accuracy. The probability of cancer for each patient was calculated entering CEA and CA 72-4 in the logistic regression model. Receiver-operating characteristic curves were constructed, and the difference in the area under the curve (AUC) values was determined between the markers and the calculated probability of cancer. Of the individual markers, the highest AUC was observed for CEA (AUC = 0.746). The difference in the AUC between CEA and CA 72-4 (AUC = 0.716) was insignificant (p = 0.492), but between CEA and the other three markers it was significant (p < 0.015). The calculated probability of cancer index, based on a combination of CEA and CA 72-4, had a significantly higher AUC (AUC = 0.804) than CEA alone (AUC = 0.746; p = 0.046). CONCLUSIONS: The diagnostic value of CA 72-4 was additive to that of CEA in colorectal cancer, and both markers contributed with significant diagnostic information. As a diagnostic test, the probability of cancer calculated with logistic regression provided higher accuracy than any of the markers alone, implying that it might be a useful diagnostic tool.

Adult↗

PubMed2004

Prognostic value of syndecan-1 expression in breast cancer.

OBJECTIVE: Syndecan-1 is a cell surface heparan sulphate proteoglycan which participates in cell proliferation, cell migration and cell-matrix interactions. Epithelial syndecan-1 expression is reduced in several malignant tumours, but in breast and pancreatic cancer, increased expression has also been described. Loss of epithelial syndecan-1 has been associated with poor prognosis in some forms of cancer, but previous findings in breast cancer have been contradictory. The objective of this study was to evaluate the prognostic value of the immunohistochemical expression of syndecan-1 in a series of 200 patients with invasive breast cancer with a median follow-up of 17 years. METHODS: Formalin-fixed paraffin-embedded specimens were stained using a monoclonal antibody against syndecan-1. RESULTS: Syndecan-1 was expressed in the epithelium in 61% and in the stroma in 67% of the tumours. Epithelial syndecan-1 expression was associated with negative oestrogen receptor (ER) status (p < 0.01), and stromal syndecan-1 expression with positive ER status (p = 0.02). The breast cancer-specific 10-year overall survival for patients with epithelial syndecan-1 expression was 65%, compared with 82% for those with loss of epithelial expression (p = 0.02). Ten-year survival was 66% for those expressing stromal syndecan-1 and 83% for those lacking stromal expression (p = 0.15). Patients with both epithelial and stromal expression had a 10-year survival of only 56%, compared to 78% in patients with other expression pattern combinations (p < 0.002). In Cox multivariate analysis, only axillary involvement and tumour size were significant predictors of breast cancer-specific survival. CONCLUSION: Concomitant expression of syndecan-1 in both epithelium and stroma may be a predictor of unfavourable prognosis in breast cancer, and in contrast with previous studies, loss of epithelial syndecan-1 was associated with a more favourable prognosis.

Adult↗

PubMed2003

Cytoplasmic HuR expression correlates with poor outcome and with cyclooxygenase 2 expression in serous ovarian carcinoma.

Cyclooxygenase-2 (COX-2) expression has been shown to associate with poor prognosis in ovarian cancer, and an mRNA stability protein HuR has been shown to enhance expression of COX-2 in tissue culture conditions. We found cytoplasmic immunoreactivity for HuR protein in 52% (233 of 445) of serous-type ovarian carcinoma specimens, and it associated with high COX-2 expression (P = 0.0045) and with clinicopathological variables, including poor prognosis (P < 0.0001) and high grade (P < 0.0001). In ovarian cancer cells in vitro, a small interfering RNA against HuR and leptomycin B, an inhibitor of nucleocytoplasmic translocation of HuR, inhibited COX-2 expression. Our results show that cytoplasmic HuR expression associates with poor outcome in ovarian cancer, and one plausible explanation for this finding may be related to the ability of HuR to induce COX-2 expression.

Adolescent↗

PubMed2003

Expression of the free beta-subunit of human chorionic gonadotropin in renal cell carcinoma: prognostic study on tissue and serum.

Expression of the free beta-subunit of human chorionic gonadotropin (hCGbeta) in malignant tumors is frequently associated with aggressive disease. We have shown previously that the pretreatment serum concentration of hCGbeta is an independent prognostic variable in patients with renal cell carcinoma (RCC). We now compare the serum levels with the expression of hCGbeta antigen and mRNA in tumor tissue and studied whether these are associated with the clinical outcome. Serum samples were collected before surgery from patients with RCC (n = 256) and from 84 apparently healthy controls. HCGbeta in serum was measured by a time-resolved immunofluorometric assay. Tissue expression was detected by immunohistochemical staining of a tissue microarray (TMA) comprising 229 samples, and in selected cases by reverse transcription polymerase chain reaction (RT-PCR) of hCGbeta mRNA (n = 20) from tumor tissue. The prognostic value of hCGbeta in serum and tissue and the association with usual clinicopathological variables was analyzed by the Kaplan-Meier method, the log-rank test, Cox multiple hazard regression, Mann-Whitney U-test or Kruskal-Wallis test. The serum concentrations of hCGbeta were increased in 27% of the RCC patients and patients with increased hCGbeta levels had significantly shorter survival time than those with levels below the median (cut-off 1.2 pmol l(-1), p = 0.0044). HCGbeta antigen was detected in 15% (35 of 229) of the tumors by immunohistochemistry, and hCGbeta mRNA in 8 of 20 samples (40%) by RT-PCR. Tissue positivity for hCGbeta antigen was not associated significantly with mRNA expression, serum concentrations of hCGbeta or survival. In multivariate analysis tumor stage, grade, size and serum hCGbeta were independent prognostic variables. The serum concentration of hCGbeta is an independent prognostic variable in RCC. Tissue expression of hCGbeta detected by immunohistochemistry occurs in 15% of RCCs but it is not significantly associated with prognosis. Expression at the mRNA level seems to be associated with other predictors of adverse outcome.

Adult↗