Biomedical subjects

Cord Langner

Publications and source records attributed to Cord Langner.

At least 37 records · Page 2Linked to original sources

PubMed2005

Annoying vacation souvenir: Fish tapeworm (Diphyllobothrium sp.) infestation in an Austrian fisherman.

Diphyllobothriosis is infestation with the fish tapeworm. Although the worldwide incidence has decreased in recent decades, increased travel and the new popularity of dishes involving raw fish (e.g. sushi) may provide a higher risk of infestation in formerly low-risk areas. We report an Austrian fisherman who passed a 75 cm tapeworm segment in his stool. Infestation presumably occurred 14 months earlier during a fishing tour in Alaska. At presentation, the patient was asymptomatic, reported no weight loss and showed neither anaemia nor eosinophilia. He was cured with a single dose of 10 mg/kg body weight praziquantel.

Alaska↗

PubMed2005

HER2 protein overexpression and gene amplification in upper urinary tract transitional cell carcinoma: systematic analysis applying tissue microarray technique.

OBJECTIVES: To investigate HER2 (c-erbB-2) protein overexpression and HER2 gene amplification in upper urinary tract transitional cell carcinoma (TCC) with respect to its association with tumor grade and stage, as well as the prognostic significance. METHODS: A total of 53 consecutive TCC specimens were analyzed immunohistochemically (HercepTest) and with fluorescence in situ hybridization applying a tissue microarray technique. RESULTS: Overall, HER2 immunoreactivity (expression) was detected in 28 of 53 TCC specimens and tended to be stronger in high-stage (8 [36%] of 22 pT1 versus 20 [65%] of 31 pT2-T3; P = 0.06) and high-grade (11 [39%] of 28 low-grade versus 17 [68%] of 25 high-grade; P = 0.054) tumors. Weak overexpression (HercepTest score 2+) was seen in 9 cases (17%) and was associated with angioinvasion (P = 0.02) and had independent prognostic significance with respect to metastasis-free survival (risk ratio 9.6; P = 0.03). Low HER2 amplification was present in four TCC specimens (9%), with HER2/chromosome 17 ratios of 2.03, 2.77, 2.91, and 3.39, and polysomy of chromosome 17 was present in another 3 cases (7%). HER2 amplification and/or polysomy of chromosome 17 prevailed in high-stage (0 [0%] of 20 pT1 versus 7 [27%] of 26 pT2-T3; P = 0.01) and high-grade (1 [4%] of 24 low-grade versus 6 [27%] of 22 high-grade; P = 0.04) tumors, but lacked independent prognostic significance. Of nine TCC specimens with weak HER2 overexpression (HercepTest score 2+), 3 (33%) showed low HER2 amplification and two others had polysomy of chromosome 17. CONCLUSIONS: HER2 overexpression and HER2 gene amplification were infrequent in our series. Thus, only a small number of patients with upper urinary tract TCC might benefit from HER2-targeted (Herceptin) cancer therapy.

Adult↗

PubMed2005

The pT1a and pT1b category subdivision in renal cell carcinoma: is it reflected by differences in tumour biology?

OBJECTIVE: To assess systematically the possible differences in pathology between pT1a and pT1b renal cell carcinomas (RCCs), as the sixth edition of the Tumour-Nodes-Metastasis (TNM) system implemented a subdivision of category pT1 into pT1a (<4 cm) and pT1b (4-7 cm), based on clinical outcome analysis and the approach to therapy. PATIENTS AND METHODS: Conventional histopathology and immunohistochemical expression of several biomarkers were analysed in 66 patients with pT1a and 29 with pT1b RCCs, using a tissue microarray technique. RESULTS: After 2 years of follow-up, none of the 66 patients with pT1a and three of the 29 with pT1b tumours developed progressive disease. The tumour was grade 3 in four (6%) pT1a and 11 (38%) pT1b RCCs. Immunohistochemically, pT1a RCCs were characterized by strong expression of p27 (79%), bcl-2 (67%), MUC1 (87%), insulin-like growth factor (IGF)-I (71%) and CD10 (88%), as well as moderate expression of IGF-I receptor (43%) and low expression of epidermal growth factor receptor (EGFR, 20%). During progression to category pT1b, expression of p27 significantly decreased (54%) and EGFR expression increased (38%). Moreover, membranous staining patterns of MUC1 and CD10 changed from apical to circumferential in clear cell RCCs. p53 (pT1a 23%, pT1b 28%), E-cadherin (10% and 17%), MIB-1 (1.2% and 1.5%) and Skp2 (2% and none) expression seemed to be of minor importance. CONCLUSION: This is the first study to show that the subdivision of category pT1 implemented in the latest issue of the TNM system is reflected by differences in conventional histopathology and expression of biomarkers.

Adult↗

PubMed2005

Kit (CD117) immunoreactivity is rare in renal cell and upper urinary tract transitional cell carcinomas.

OBJECTIVE: To investigate the presence of Kit (CD117), a transmembrane tyrosinase-kinase receptor, in primary and metastatic renal cell carcinomas (RCCs) and upper urinary tract transitional cell carcinomas (TCCs). MATERIALS AND METHODS: In human neoplasia, overexpression of Kit has been related to cell proliferation, differentiation, adhesion and control of apoptosis. If present, Kit may provide a suitable target for tumour therapy. Formalin-fixed and paraffin-embedded specimens of 180 primary and 58 metastatic RCCs and 54 upper urinary tract TCCs were immunostained for Kit (CD117) using a tissue microarray technique. RESULTS: In RCCs, immunoreactivity for CD117 was detected in only two of 23 (9%) chromophobe tumours, whereas all 137 conventional and 20 papillary subtypes, and metastatic RCC tissues, lacked CD117 immunoreactivity. In TCCs, CD117 expression of <10% cancer cells was found in two of 53 (4%) cases. Stromal mast cells served as a positive control and showed specific immunostaining. CONCLUSION: Kit immunoreactivity is infrequent in both RCCs and upper urinary tract TCCs. Thus, routine screening of tumour tissues for Kit by immunohistochemistry appears to be cost-ineffective and cannot be recommended. Moreover, the lack of substantial Kit immunoreactivity in both primary and metastatic carcinomas does not provide a rationale to investigate imatinib mesylate therapy in clinical trials including patients with advanced disease.

Adult↗

PubMed2004

Biological significance of p27 and Skp2 expression in renal cell carcinoma. A systematic analysis of primary and metastatic tumour tissues using a tissue microarray technique.

p27 (p27/kip1) is involved in cell-cycle control, and loss of p27 expression may result in tumour development and/or progression. Association with Skp2 targets p27 for degradation. Using a tissue microarray technique, 171 primary renal cell carcinomas (RCCs) and 58 RCC metastases were immunostained for p27 and Skp2. p27 Immunoreactivity was noted in 83 of 129 (64%) clear cell, 6 of 22 (27%) chromophobe and 15 of 20 (75%) papillary tumours as well as 44 of 58 (76%) metastases. In clear cell cancers, high p27 expression (> or =50% of tumour cells) decreased with rising tumour stage (50% pT1/pT2 versus 20% pT3; P<0.001) and grade (44% G1/G2 versus 21% G3/G4; P=0.008). None of 22 chromophobe cancers showed high expression in contrast to 46 of 129 (36%) clear cell tumours (P<0.001). Skp2 expression was noted in 8 of 129 (6%) clear cell cancers and 11 of 55 (20%) metastases (P=0.008). Immunoreactivity increased with rising tumour stage (1% pT1/pT2 versus 11% pT3; P=0.03) and grade (1% G1/G2 versus 15% G3/G4; P=0.004) and was associated with sarcomatoid morphology (P<0.001). In multivariate analysis, patients with low p27 expression and Skp2 immunoreactivity in clear cell cancers had a less favourable outcome. In conclusion, p27 and Skp2 proved to be additional biomarkers in renal cancer pathology with both prognostic and diagnostic impact.

Adult↗

PubMed2004

Prognostic value of keratin subtyping in transitional cell carcinoma of the upper urinary tract.

To investigate the prognostic value of keratin subtyping in invasive transitional cell carcinomas (TCCs), we performed a systematic study applying 15 different monoclonal keratin antibodies on 53 upper urinary tract TCCs using a tissue microarray technique. Immunoreactivity was correlated with pT stages and tumour grades using the Fisher's exact test. Impact on disease-free survival was analysed using the Kaplan-Meier method and compared by the log-rank test. Immunoreactivity for keratins 5/6, 6, 7, 8, 13, 14, 17, 18, 19, 20, low molecular weight (LMW) keratins (8, 18) and high molecular weight (HMW) keratins (1, 5, 10, 14) was detected in varying quantities. Regarding semi-quantitative assessment, a prognostic impact was found for keratins 5/6, 7, 8, 13, 17, 20 and HMW keratins, with reduced expression or loss of immunoreactivity being significantly associated with disease progression. With respect to analysis of staining patterns, the retention of a basally accentuated labelling for keratin 5/6 and HMW keratin as well as a superficially accentuated labelling for keratin 20 was significantly associated with a favourable outcome. In conclusion, this investigation is the first to demonstrate a possible prognostic value for keratin subtyping in invasive (upper urinary tract) TCCs with respect to metastasis-free survival. Further studies, however, are needed to substantiate our results.

Adult↗

PubMed2004

Minimally invasive management of dysontogenetic hepatic cysts.

BACKGROUND: Liver cysts occur with a prevalence of 4%-7% in the general population. Laparoscopic surgery is effective for solitary cysts and in selected patients with polycystic liver disease (PLD). We present our experience in the laparoscopic management of dysontogenetic cysts. PATIENTS AND METHODS: Between 1994 and 2002, 36 patients were referred to our centre for the management of dysontogenetic cystic liver disease. Management was laparoscopic in 16 cases. Indications were solitary giant cysts (n=9) and PLD (n=7). RESULTS: Laparoscopic procedures were completed in 15 patients. Mean operating time was 90 min. There were no deaths. In one case there was an intraoperative complication: bleeding from a superficial hepatic vein necessitated conversion to an open procedure. There were two postoperative complications: one patient with biliary leakage, which was managed conservatively, and one patient with a pneumothorax caused by the cava catheter installed for anaesthesia. Median follow-up was 36 months. There was no symptomatic recurrence. CONCLUSION: Laparoscopy can be recommended as the procedure of choice for symptomatic solitary giant cysts and PLD Gigot type I.

Adult↗

PubMed2004

Wilson disease.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. Since daily copper intake exceeds the body's requirements, effective means of excreting excess copper are essential. These are accomplished by ATP7B, a new member of the cation-transporting p-type ATPase family, which is mainly expressed in the liver and mediates both copper secretion into plasma (coupled with ceruloplasmin synthesis) and its excretion into bile. Thus far, more than 200 mutations of the WD gene have been detected, causing impairment of ATP7B function and, ultimately, copper accumulation. Excess copper, however, induces free-radical reactions and lipid peroxidation. Resultant liver damage leads to steatosis, inflammation, cirrhosis, and, occasionally, fulminant liver failure. The diagnosis of WD is commonly made on the basis of typical clinical and laboratory findings, including low serum ceruloplasmin, increased urinary copper excretion, and increased hepatic copper content. Since liver morphology is non-specific, and copper histochemistry may lead to both false-negative and false-positive results, the pathologist usually only suspects the disease or assists in its confirmation. Although the value of molecular genetic testing is limited due to the high number of possible gene mutations, polymerase chain reaction may be useful for the evaluation of family members of homozygous index patients.

Copper↗

PubMed2004

Keratin immunohistochemistry in renal cell carcinoma subtypes and renal oncocytomas: a systematic analysis of 233 tumors.

Keratin immunohistochemistry represents a widely applied differential diagnostic tool in surgical pathology. To investigate the value of keratin subtyping for the diagnosis among histological subtypes of renal cell carcinoma and oncocytomas, we performed a detailed immunohistochemical study, applying 22 different monoclonal keratin antibodies on a large series of 233 renal tumors [125 conventional, 22 chromophobe, and 20 papillary (12 type-1, 8 type-2 tumors) cancers and 66 oncocytomas] using a tissue microarray technique. Immunoreactivity for keratin 7, 8, 18, and 19 was present in all tumor entities, albeit in varying quantities. With antibodies directed against keratins 8 and 18, oncocytomas showed a distinct perinuclear and punctate dot-like pattern, which was not observed in renal cancer specimens. The only tumors showing immunoreactivity for keratin 20 were two type-2 papillary cancers. All other monospecific keratin antibodies yielded consistently negative results. Overall, in contrast to some recent publications, keratin subtyping generally appeared to be of additional value only for the differentiation of renal epithelial tumors. Hence, with respect to differential diagnostic value, Hale's colloidal iron stain and vimentin immunostaining are still the most useful tools in renal tumor pathology.

Adenoma, Oxyphilic↗

PubMed2004

Immunohistochemical analysis of Mallory bodies in Wilsonian and non-Wilsonian hepatic copper toxicosis.

Patients with Wilson's disease (WD), Indian childhood cirrhosis (ICC), and idiopathic copper toxicosis (ICT) develop severe liver disease morphologically characterized by ballooning of hepatocytes, inflammation, cytoskeletal alterations, and Mallory body (MB) formation, finally leading to mostly micronodular cirrhosis. The pathogenesis of MBs in copper toxicosis is still unresolved. Immunohistochemical analysis of MBs in different types of copper intoxication revealed that keratin, p62, and ubiquitin are integral components. Thus MBs associated with copper intoxication resemble those present in alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). p62 is a multifunctional immediate early gene product that, on the one hand, is involved in stress-induced cell signaling (particularly that of oxidative stress) by acting as an adapter protein linking receptor-interacting protein (RIP) with the atypical protein kinase C. On the other hand, p62 binds with high affinity to polyubiquitin and ubiquitinated proteins. In conclusion, p62 accumulation in WD, ICC, and ICT and deposition in MBs indicates a central role of protein misfolding induced by oxidative stress in copper-induced liver toxicity. By sequestering potentially harmful misfolded ubiquitinated proteins as inert cytoplasmic inclusion bodies (e.g., as MBs), p62 may be a major player in an important cellular rescue mechanism in oxidative hepatocyte injury.

Adolescent↗

PubMed2004

Value of p53 as a prognostic marker in histologic subtypes of renal cell carcinoma: a systematic analysis of primary and metastatic tumor tissue.

OBJECTIVES: To investigate the histologic subtypes of renal cell carcinoma (RCC) with respect to differences in immunoreactivity for p53 and its impact on prognosis. The prognostic significance of p53 in RCC remains to be defined. METHODS: A total of 188 primary RCC and 58 RCC metastasis specimens were stained immunohistochemically for p53 overexpression using a tissue microarray technique. p53 overexpression was analyzed semiquantitatively with respect to its association with pT stage, grade, histologic subtype, and sex using the chi-square test or Fisher's exact test. The impact on metastasis-free survival was analyzed using the Kaplan-Meier method and log-rank test. For conventional RCC, a multivariate analysis, including pT stage, grade, and p53 immunoreactivity was performed. RESULTS: Sufficient tumor tissue was present in 184 (97.9%) of 188 primary and 56 (96.6%) of 58 metastatic cases. p53 overexpression was found in 42 (22.8%) of 184 primary RCC specimens and in 29 (51.8%) of 56 metastasis specimens (P = 0.0001). p53 overexpression for papillary, chromophobe, and conventional RCC was 70.0%, 27.3%, and 11.9%, respectively (P <0.0001). No association of p53 immunoreactivity with the other parameters investigated was found. Regarding prognosis, a statistically significant difference in metastasis-free survival between p53-positive and p53-negative tumors was found only for conventional RCC (P = 0.0005) and not for the other subtypes (P = 0.19). Multivariate analysis proved grade (P <0.0001), pT stage (P = 0.01), and p53 overexpression (P = 0.01) to be independent prognostic factors for conventional RCC. CONCLUSIONS: p53 overexpression was significantly more frequent in "nonconventional" RCC subtypes, especially papillary RCC, compared with conventional RCC in our study. However, p53 immunoreactivity is a prognostic marker only for conventional RCC.

Adult↗

PubMed2004

Prognostic impact of p63 and p53 expression in upper urinary tract transitional cell carcinoma.

OBJECTIVES: To analyze p63 and p53 immunoreactivity of upper urinary tract transitional cell carcinoma with respect to prognosis. p63 is required for the differentiation of normal urothelium and is expressed in both non-neoplastic urothelium and transitional cell carcinoma of the bladder. METHODS: A total of 53 upper urinary tract transitional cell carcinoma specimens were investigated immunohistochemically using a tissue microarray technique. p63 and p53 immunoreactivity was analyzed digitally with respect to associations with pT stage and grade and impact on disease-free survival. RESULTS: p63 expression was detected in 51 (96.2%) of 53 cases. Normal expression (greater than 90% of tumor cell nuclei) was observed in 1 (4.5%) of 22 Stage pT3 compared with 13 (41.9%) of 31 Stage pT1-T2 tumors (P = 0.003) and 4 (16%) of 25 G3 compared with 10 (35.7%) of 28 G2 tumors (P = 0.13). p53 overexpression (more than 10% of tumor cell nuclei) was found in 10 (18.9%) of 53 cases, including 2 (6.5%) of 31 Stage pT1-T2 and 8 (36.4%) of 22 Stage pT3 (P = 0.011) and 0 of 28 G2 and 10 (40%) of 25 G3 tumors (P <0.001). Metastatic disease was observed in 14 (26.4%) of 53 patients, including none of 14 with normal p63 expression compared with 14 (35.9%) of 39 with decreased (less than 90% of tumor cell nuclei) p63 expression (P = 0.02) and 5 (50%) of 10 patients with p53 overexpression compared with 9 (20.9%) of 43 patients with p53-negative tumors (P = 0.01). Multivariate analysis proved Stage pT3 was the only independent prognostic factor. CONCLUSIONS: Decreased p63 immunoreactivity and p53 overexpression were significantly associated with advanced tumor stages and poor prognosis. However, neither parameter was an independent prognostic factor in multivariate analysis.

Adult↗

PubMed2004

Expression of p27 and its ubiquitin ligase subunit Skp2 in upper urinary tract transitional cell carcinoma.

OBJECTIVES: To analyze p27 and S-phase kinase-associated protein 2 (Skp2) expression in upper urinary tract transitional cell carcinoma (TCC) with respect to biologic significance. p27 (p27/kip1) is involved in cell cycle control, and loss of p27 protein expression may result in tumor development and/or progression. The association of p27 with the ubiquitin ligase subunit Skp2 targets p27 for degradation. METHODS: A total of 53 upper urinary tract TCC specimens were investigated immunohistochemically using a tissue microarray technique. The immunoreactivity of p27 and Skp2 was analyzed with respect to associations with pT stage, grade, and prognosis. RESULTS: Non-neoplastic renal tissue showed p27 immunoreactivity in tubule epithelium and pelvic urothelium, but lacked immunoreactivity for Skp2. In the TCC specimens, p27 immunoreactivity was noted in 47 (89%) of 53 cases. High p27 expression (50% or greater of tumor cell nuclei) tended to decrease with rising tumor stage (14 [45%] of 31 with pT1-pT2 versus 4 [18%] of 22 with pT3; P = 0.076), but was independent of tumor grade (11 [39%] of 28 grade 2 versus 7 [28%] of 25 grade 3-4; P = 0.56). Skp2 immunoreactivity was noted in 32 (60%) of 53 tumors. Skp2 expression increased with rising tumor stage (9 [41%] of 22 pT1 versus 23 [74%] of 31 pT2-pT3; P = 0.023) and tumor grade (12 [43%] of 28 grade 2 versus 20 [80%] of 25 grade 3; P = 0.043) and was associated with angioinvasion (P = 0.017). In multivariate analysis, tumor stage proved to be the only independent prognostic factor regarding disease-free survival. CONCLUSIONS: p27 and Skp2 are additional biomarkers in urogenital pathologic findings. The statistically significant association of Skp2 expression with high-grade TCC, as well as the lack of expression in non-neoplastic tissue, suggests that Skp2 could be a promising target for future cancer therapy strategies.

Adult↗

PubMed2004

Expression of MUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic immunohistochemical analysis of 188 cases.

MUC1 (epithelial membrane antigen) is a membrane-associated mucin known to interfere with both cell-cell and cell-matrix adhesions. Overexpression has been associated with poor prognosis in a variety of cancers. We investigated the expression of MUC1 (using two different antibodies, MA695 and E29) and E-cadherin in renal cell carcinomas (137 conventional, 23 chromophobe, 20 papillary, and eight unclassified tumors) with respect to diagnostic and prognostic significance using a tissue microarray technique. Immunoreactivity was correlated with histological subtype, pT-stage, and grade using the chi2 test or the Fisher's exact test, respectively. Impact on disease-free survival was analyzed using the Kaplan-Meier method and the log-rank test. Immunoreactivity of more than 10% of cancer cells with MA695, E 29, and E-cadherin antibodies was found in 112/133 (84%), 86/133 (65%), and 7/131 (5%) conventional, 20/22 (91%), 19/22 (86%), and 21/22 (95%) chromophobe, 13/20 (65%), 8/20 (40%), and 3/20 (15%) papillary as well as 5/8 (63%), 5/8 (63%), and 4/8 (50%) unclassified carcinomas, respectively. The two different MUC1 antibodies yielded comparable staining results. A diffuse cytoplasmic staining pattern for MUC1 was found exclusively in chromophobe carcinomas, whereas conventional and papillary subtypes showed predominantly membranous staining (P<0.0001). Regarding papillary carcinomas, MUC1 was predominantly associated with type 1 (P=0.0001), and E-cadherin with type 2 (P=0.049) tumors. The cellular staining pattern of MUC1 in conventional tumors was related to pT-stage (P=0.002) and tumor grade (P=0.001): Low-stage (pT1/pT2) and grade (G1/G2) tumors showed a predominantly apical membranous staining, high-stage (pT3a/pT3b) and grade (G3/G4) tumors a predominantly circumferential membranous staining (with or without additional diffuse cytoplasmic immunoreactivity), which, in the conventional subtype, was associated with poor prognosis (P<0.0001). In conclusion, MUC1 and E-cadherin are diagnostically and prognostically useful markers in renal tumor pathology, especially when cellular staining patterns are considered.

Adult↗

PubMed2004

Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice.

BACKGROUND & AIMS: Because the mechanisms leading to bile duct damage in sclerosing cholangitis are unknown, we aimed to determine the pathogenesis of bile duct injury in multidrug resistance gene (Mdr2) (Abcb4) knockout mice (Mdr2(-/-)) as a novel model of the disease. METHODS: Mdr2(-/-) and wild-type controls (Mdr2(+/+)) were studied at 2, 4, and 8 weeks of age. Liver histology, ultrastructure, immunofluorescence microscopy (to study inflammatory cells, tight junction protein ZO-1, basement membrane protein laminin, fluorescence-labeled ursodeoxycholic acid), immunohistochemistry (for alpha-smooth muscle actin, nitrotyrosine), sirius red staining, bacterial cultures of intra-abdominal organs, and polymerase chain reaction (PCR) for Helicobacter bilis DNA were compared between both genotypes. Hepatic cytokine expression was determined by reverse-transcription PCR. RESULTS: Bile ducts of Mdr2(-/-) showed disrupted tight junctions and basement membranes, bile acid leakage into portal tracts, induction of a portal inflammatory (CD11b, CD4-positive) infiltrate, and activation of proinflammatory (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta) and profibrogenic cytokines (transforming growth factor [TGF]-beta1). This resulted in activation of periductal myofibroblasts, leading to periductal fibrosis, separating the peribiliary plexus from bile duct epithelial cells and, finally, causing atrophy and death of the bile duct epithelium. Bacterial translocation was not increased and H. bilis was not detectable in Mdr2(-/-). CONCLUSIONS: Sclerosing cholangitis in Mdr2(-/-) mice is a multistep process with regurgitation of bile from leaky ducts into the portal tracts, leading to induction of periductal inflammation, followed by activation of periductal fibrogenesis, finally causing obliterative cholangitis owing to atrophy and death of bile duct epithelial cells.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2004

Steroid hormone receptor expression in renal cell carcinoma: an immunohistochemical analysis of 182 tumors.

PURPOSE: Steroid hormone receptor expression has an essential role in cancer of the prostate and breast but there is only limited experience with renal cell carcinoma (RCC), especially regarding prognostic and therapeutic impact. MATERIALS AND METHODS: A total of 188 cases of RCC were stained immunohistochemically for the expression of estrogen (ER), progesterone (PR) and androgen (AR) receptors using a tissue microarray technique. Nuclear steroid hormone receptor immunoreactivities were analyzed semiquantitatively with respect to associations with histological subtype, pT stage, grading and gender using Fisher's exact test. Impact on disease-free survival was analyzed using the Kaplan-Meier method. RESULTS: Sufficient tumor tissue was present in 182 of the 188 RCCs. AR expression was found in 27 of 182 tumors (14.8%) in 24 male and 3 female patients. AR expression was significantly associated with stage pT1 compared with pT3 (p <0.0001), and grades 1 and 2 compared with grade 3 (p = 0.0005). Regarding progression-free survival, AR positive RCCs showed a significantly better prognosis than AR negative cases (log rank test, p = 0.027). No difference of AR immunoreactivity could be detected between histological subtypes. Only 2 of the 182 cases (1.1%) showed ER and PR immunoreactivity in less than 10% of tumor cell nuclei. CONCLUSIONS: While ER and PR expression was the exception, AR expression was found in almost 15% of the tumors and it was significantly associated with low stage, well or moderately differentiated tumors and a favorable outcome, decreasing with tumor growth and dedifferentiation. However, these results do not support a potential role of hormonal therapy for metastatic RCC.

Adult↗

PubMed2004

Analysis of insulin-like growth factors and insulin-like growth factor I receptor expression in renal cell carcinoma.

The expression of insulin-like growth factors I (IGF-I) and II (IGF-II) and insulin-like growth factor-I receptor (IGF-IR) was studied in 137 clear cell, 23 chromophobe, and 20 papillary renal cell carcinomas (RCCs) using a tissue microarray technique. IGF-I immunoreactivity was detected in 110 (82.1%) of 134 clear cell, 8 (36%) of 22 chromophobe, and 3 (15%) of 20 papillary RCCs (P < .001). IGF-IR immunoreactivity was detected in 39 (29.5%) of 132 clear cell, 9 (41%) of 22 chromophobe, and 19 (95%) of 20 papillary RCCs (P < .001). In contrast, all tumors lacked IGF-II expression. Expression of IGF-I and IGF-IR was not related to tumor stage, grade, or prognosis. The IGF system is expressed differentially among different tumor types. The expression of IGF-I together with its receptor, IGF-IR, provides evidence for the existence of an autocrine-paracrine loop of tumor cell stimulation in RCC and makes this type of cancer a candidate for therapeutic strategies aimed to interfere with the IGF pathway.

Adult↗

PubMed2003

IGF-1R, IGF-1 and IGF-2 expression as potential prognostic and predictive markers in colorectal-cancer.

Insulin-like growth factors (IGF-1 and IGF-2) and the IGF-1 membrane receptor (IGF-1R) have been found to play a critical role in the carcinogenesis of several tumors, among them colorectal cancer (CRC). To study the prognostic impact of these molecules, a total number of 713 cases of CRC were examined for the expression of IGF-1, IGF-2, and IGF-1R. The results were correlated with other clinicopathological data and clinical follow-up. IGF-1 expression was noted in 53 (7.5%), IGF-2 in 88 (12.6%), and IGF-1R in 698 (99.6%) of the cases. There were significant associations between the two growth factors ( P<0.00001), between IGF-1 and Ki-67 proliferation activity ( P<0.05), and between IGF-2 and tumor stage ( P<0.005). IGF-2 positivity was significantly correlated to a worse clinical outcome ( P<0.005) only in univariate, but not in multivariate, survival analysis. A similar trend was obtained for patients with IGF-1-positive CRC, but reached statistical significance only in limited tumor stages (pT1/pT2; P<0.01). Although the synchronous expression of IGF-1, IGF-2, and IGF-1R in a subset of CRC is consistent with an auto-/paracrine loop of cancer cell autostimulation, the prognostic effect of IGF-1 and IGF-2 expression seems to be of limited value. However, the identification of IGF-positive CRC might be beneficial for predictive reasons, as new molecular therapeutic approaches are aimed at the IGF system and related pathways.

Adenocarcinoma↗