Alpha-methylacyl-CoA racemase (AMACR/P504S) protein expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression

Alpha-methylacyl-CoA racemase (AMACR/P504S) is a useful biomarker of prostate cancer. We evaluated the expression of AMACR in upper urinary tract urothelial carcinomas with respect to associations with tumour stage, grade and metastasis-free survival. A total of 268 tumours were investigated immunohistochemically using a tissue microarray technique. AMACR expression was noted in 127 of 261 (48.7%) evaluated tumours and was associated with high tumour stage [58 of 139 (41.7%) pTa/pT1 vs. 69 of 122 (56.6%) pT2–pT4, P=0.019] and high tumour grade [44 of 137 (32.1%) low vs. 83 of 124 (66.9%) high grade, P<0.001]. In addition, AMACR expression was associated with the presence of tumour necrosis (P<0.001) and marked stromal desmoplasia (P=0.0026). This correlation indicates that increased AMACR expression might be related to hypoxia-induced changes in cancer cell metabolism, such as increased dependence on fatty acid oxidation for energy generation. Progressive disease was observed in 73 of 183 (39.9%) patients with solitary invasive carcinomas and was associated with AMACR expression (P=0.017). Multivariate analysis, however, proved only pT-stage >1 (P<0.001) and high tumour grade (P<0.001) to be independent predictors of patient outcome. In conclusion, AMACR expression correlated with advanced tumour stage and grade and may serve as an additional prognostic indicator in upper urinary tract urothelial cancer.     

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 (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.     

The pathological response to neoadjuvant chemotherapy with FOLFOX-4 for colorectal liver metastases: a comparative study

FOLFOX-4 (folinic acid/5-fluorouracil/oxaliplatin) chemotherapy is used to treat patients with colorectal liver metastases. We aimed to assess hepatic histopathological responses to neoadjuvant FOLFOX-4 chemotherapy in patients with colorectal liver metastases. We selected all patients (n = 54) treated with FOLFOX-4 for colorectal liver metastases between June 2002 and June 2005. Only 25 underwent hepatectomy and formed the study group. Histological responses were assessed in the study group and a matched control group (n = 25) that did not receive neoadjuvant chemotherapy. The median (IQR) body mass index in the study and control groups was 24 (22–26) and 24 (23–25) kg/m², respectively, (P = NS). Complete histological resolution of tumour occurred in six (24%) patients in the study group. Median residual tumour cellularity was less (35 vs 70%) and fibrosis greater (50 vs 5%) in patients in the study group when compared with controls (P < 0.001). The liver surrounding the tumour was steatotic in 17 (68%) patients in the study group and five (20%) controls (P = 0.001). Hepatic sinusoidal dilatation was more pronounced in patients in the study group than in controls (P < 0.001). The response to FOLFOX-4 was associated with tumour necrosis, fibrosis and inflammation. More than two thirds of patients undergoing hepatectomy after FOLFOX-4 had steatosis despite being non-obese.     

Clinicopathological significance of WT1 expression in ovarian cancer: a possible accelerator of tumor progression in serous adenocarcinoma

Recently, oncogenic potential of the WT1 gene has been proposed in some human solid tumors and leukemias. Although previous studies have shown the frequent expression of the WT1 protein in ovarian serous adenocarcinomas (OSAs), its clinicopathologic significance is still unclear. We immunohistochemically examined the expression status of WT1 in 119 OSAs and analyzed the correlation of the intensity of WT1 immunoreactivity with the level of WT1 mRNA expression by quantitative real-time polymerase chain reaction, clinicopathologic variables, expression of p53, Bcl-2, and Ki-67 labeling index (LI). Of 119 OSAs, nuclear WT1 immunoreactivity was positive in 99 (83%), of which 44 (44%) and 55 (56%) exhibited high and low WT1 immunoreactivities, respectively. The quantitative WT1 mRNA levels were significantly correlated with the intensity of WT1 immunoreactivity (P < 0.05). In comparison with WT1-negative OSAs, the WT1-positive OSAs showed a higher grade (P = 0.007), advanced stage (P = 0.018), and higher Ki-67 LI (P < 0.001). Additionally, high WT1 immunoreactivity was correlated with a higher grade (P = 0.003), Ki-67 LI (P = 0.012), Bcl-2 expression (P = 0.003), and poorer patient outcome (5-year survival, 36.5 vs 63.8%, P = 0.008 by log-rank test). The WT1 protein may be an accelerator of the progression of OSA.     

Patterns of invasion and histological growth as prognostic indicators in urothelial carcinoma of the upper urinary tract

The biological significance of squamous and glandular differentiation and different patterns of invasion in upper urinary tract urothelial carcinoma is unclear. We reviewed 268 cases of consecutive upper urinary tract carcinomas with respect to the presence of squamous and/or glandular differentiation and different patterns of invasion (nodular, trabecular, and infiltrative) and correlated data with patient outcome. Squamous or glandular differentiation occurred in 47/268 (18%) tumors and its presence correlated with high tumor stage (P<0.001) and grade (P<0.001). Invasive patterns were nodular in 49/227 (22%), trabecular in 95/227 (42%), and infiltrative in 83/227 (37%) tumors. The nodular pattern prevailed in low stage (P<0.001) and low-grade (P<0.001) tumors, whereas the infiltrative pattern prevailed in high stage (P<0.001) and high-grade (P<0.001) tumors. Multivariate analysis proved that tumor stage (P<0.001) and the infiltrative pattern (P<0.001) are independent predictors of metastasis-free survival, whereas tumor grade and squamous and glandular differentiation lacked independent influence on patient outcome. In conclusion, the infiltrative pattern of invasion significantly correlated with advanced disease and poor patient outcome. In contrast, the presence of squamous and/or glandular invasion did not prove independent influence on patient outcome. The pattern of invasion should be commented upon separately in the pathology report.     

Overexpression of carbonic anhydrase IX (CAIX) is an independent unfavorable prognostic marker in endometrioid ovarian cancer

Carbonic anhydrase IX (CAIX) is a strictly membranous expressed metalloenzyme involved in cell adhesion, pH homeostasis, and cancer progression. This study was designed to assess the role of CAIX in primary ovarian cancer. Two hundred five well-characterized primary ovarian carcinomas were analyzed on a tissue microarray. CAIX expression was determined by immunohistochemistry using a four-step scoring system. Moderate and strong membranous CAIX expression was found in 37 out of 205 (18%) of all assessable ovarian cancer specimens. High levels of CAIX expression were related to mucinous and endometrioid phenotype of ovarian carcinomas (p < 0.05). There was no association between CAIX overexpression and tumor stage, grading, and mitotic count of ovarian carcinomas (p > 0.05). In univariate Cox regression analysis, advanced tumor stage (p < 0.01), high tumor grade (p = 0.017), high mitotic count (p = 0.025), and high CAIX expression levels (p = 0.031) were correlated to shorter overall patient survival. High pT stage (p = 0.036) and CAIX overexpression were connected to poor clinical outcome in endometrioid ovarian carcinomas. Multivariate Cox regression hazard analysis comprising tumor stage, tumor grade, mitotic count, and CAIX expression revealed pT2/3 stage and CAIX overexpression (scores 2 and 3) as independent prognostic markers in ovarian cancer (p < 0.01, each) as well as in the subgroup of endometrioid carcinomas (p < 0.05, each). In conclusion, CAIX is overexpressed in a substantial proportion of mucinous and endometrioid ovarian carcinomas and connected to poor patient outcome. Our data support the potential therapeutic benefit of newly developed targeting antibodies in advanced ovarian cancer.     

Immunohistochemical expression of p63, p53 and MIB-1 in urinary bladder carcinoma. A tissue microarray study of 158 cases

P63 is a member of the p53 family, which plays a role in the differentiation of urothelium and is supposed to play a role in urothelial carcinogenesis. P53 and MIB-1 are recognised in many studies as predictive markers of progression, but few studies in the literature have examined p63. The aims of our study were to explore the expression of p63 in bladder carcinomas and to compare this expression to p53 and MIB-1, as well as to stage and grade. Tissue microarrays were performed on 158 urothelial carcinomas (56 pTa, 45 pT1 and 57≥pT2). Immunohistochemical studies were performed with p63, p53 and MIB-1 antibodies. In our study we observed that p63 immunostaining is present in all cell layers in papillary urothelial neoplasm of low malignant potential (PUNLMP), but partially lost in non-invasive papillary urothelial carcinoma low grade (NILGC) and in pT1/≥pT2 bladder cancers. P53 and MIB-1 displayed lower expression in PUNLMP/NILGC vs non-invasive papillary urothelial carcinoma high grade (NIHGC)/pT1, but there was no correlation between the expression of p63, p53 and MIB-1. Our study demonstrates that p63 expression distinguishes between PUNLMP/NILGC and NIHGC/pT1 (p=4.10⁵). A statistical difference disserving pTa and pT1/≥pT2 with a statistical significance (p<10⁻⁶) could also be observed. P63 should be considered as an additional biomarker that might help pathologists to classify their patients.     

Prognostic role of CD44 cell adhesion molecule expression in primary and metastatic renal cell carcinoma: a clinicopathologic study of 125 cases

Possible prognostic utility of CD44 in renal cell carcinoma (RCC) prompted a comparison of its expression in primary and metastatic RCC. A total of 164 paraffin-embedded tissues of primary RCC and metastatic RCCs from 125 patients were immunostained with CD44 (standard form) antibody. It consisted of 86 primary RCCs (50 with subsequent metastasis [MET+] and 36 with no known metastasis [MET−]) during follow up and 78 metastatic RCCs (39 metastatic RCCs only and 39 with matched RCC primary from RCC MET + category). Immunoreactivity for CD44 was scored semiquantitatively as 0, 1, or 2 (0, <5%; 1, 5–50%; 2, ≥50%). Expression of CD44 was significantly higher in metastatic RCCs compared to primary RCCs (p = 0.036). CD44 immunoreactivity in the primary RCC (MET− and MET+) correlated with progression-free survival (p = 0.027). In metastatic RCCs, CD44 immunoreactivity also correlated with survival after detection of first metastasis (p = 0.011). In multivariate analysis, stage (p = 0.0001) and CD44 immunoreactivity (p = 0.03) in primary RCC were independent predictors of progression-free survival. Our study suggests that CD44 status in RCC provides useful prognostic information both in primary and metastatic RCCs and may have applicability in stratifying patients for therapeutic decisions.     

Histological grading in a large series of advanced stage ovarian carcinomas by three widely used grading systems: consistent lack of prognostic significance. A translational research subprotocol of a prospective randomized phase III study (AGO-OVAR 3 protocol)

While there is no doubt that histologic grading is applicable in early stage ovarian carcinoma, it is still in controversial discussion concerning advanced stage ovarian carcinoma. It was the aim of this study to assess the three most widely used grading systems for ovarian carcinoma in terms of prognostic significance, concordance rates, and reproducibility in a large number of advanced stage ovarian carcinomas of all types after standardized chemotherapy. Representative hematoxylin and eosin slides from 334 cases of stage IIB–IV ovarian carcinoma (prospective randomized, multi-center, phase III study) were used. The first round was grading of all cases according to FIGO, GOG, and Silverberg by one author. The second round (after 1 year) was 30 randomly selected cases graded by three authors. None of the three grading systems was prognostically significant (FIGO p = 0.38; GOG p = 0.70; Silverberg p = 0.92). The concordance rates between the three systems were as follows: FIGO/GOG 95.5%, κ = 0.929; Silverberg/FIGO 69.9%, κ = 0.533; Silverberg/GOG 66.8%, κ = 0,481. Grading of advanced stage ovarian carcinomas was of no value for estimation of prognosis in this homogeneously treated patient group. Alternative methods should be defined, which might help to separate patients with high risk of tumor progression from others with low risk.     

Expression of CD62L on Donor CD4<Superscript>+</Superscript> T Cells in Allografts: Correlation with Graft-Versus-Host Disease after Unmanipulated Allogeneic Blood and Marrow Transplantation

Introduction  The aim of this study was to investigate the association of donor CD4⁺ T cells expressing CD62L with transplant outcomes. Materials and Methods  We report a prospective analysis of 31 patients who were treated with a Bu/Cy regimen, followed by unmanipulated blood and marrow transplantation. Results  Median number (range) of CD4⁺CD62L⁺, CD4⁺CD45RA⁺CD62L⁺, and CD4⁺CD45RO⁺CD62L⁺ cells infused were 0.31(0.05–1.10)×10⁸/kg, 0.22(0.03–0.95)× 10⁸/kg, and 0.17(0.01–0.81)×10⁸/kg, respectively. The incidence of grades II to IV aGVHD was 36%. In a multivariate analysis, infusion of >0.22 × 10⁸ CD4⁺CD45RA⁺CD62L⁺ cells infused/kg increased the risk of grades II to IV aGVHD (HR = 4.741, 95% CI = 1.037–21.662, P = 0.045). Thirteen of 31 patients experienced cGVHD, the risk of cGVHD was increased in patients receiving >0.45 × 10⁸ CD4⁺CD45RA⁺ cells infused/kg (HR = 4.614, 95% CI = 1.265–16.829, P = 0.021). Conclusion  Our results suggest that a high cell dose of CD4⁺CD45RA⁺CD62L⁺ cells increase the incidence of grades II–IV aGVHD. A high number of CD4⁺CD45RA⁺ cells infused were associated with increased risk of cGVHD in our transplant settings. Ying-Jun Chang: performed research, analysis and interpretation of data, and drafting of the article, and gave final approval of the version to be published; Xiang-Yu Zhao: performed research, analysis and interpretation of data, and drafting of the article and gave final approval of the version to be published; Ming-Rui Huo: performed research, analysis and interpretation of data, and drafting of the article and gave final approval of the version to be published; Xiao-Jun Huang: involved in conception and design, revising the article critically, and final approval of the version to be published.     

Seroprevalence and sources of Toxoplasma infection among indigenous and immigrant pregnant women in Taiwan

Investigation on seroprevalence and risk factors of Toxoplasma gondii infections among indigenous and immigrant pregnant women in Mid-Taiwan showed that anti Taxoplasma-specific IgG antibody counts were significantly higher in indigenes (40.6%) than in immigrants (18.2%), with an odds ratio of OR = 3.34 (95% CI: 1.93–4.80). The titre of Taxoplasma-specific IgG was also significantly higher in indigenes than in immigrants (P < 0.001). Differences of living styles for Toxoplasma infection between the two groups were drinking untreated water (OR = 2.34, 95% CI: 1.36–4.02), consumption of raw/undercooked meats (OR = 10.11 95% CI: 4.92–20.78), especially raw/undercooked pork (P = 0.000), or raw/undercooked viscera (OR = 9.16, 95% CI: 2.97–27.94), contact with cats (OR = 5.69, 95% CI: 2.83–11.47), or soil (OR = 2.55 95% CI: 1.72–3.80). Differences of risk factors for Toxoplasma infection in terms of positive IgG in the two groups were consumption of raw/undercooked meats (P = 0.005) especially raw/undercooked pork (P = 0.004), and contact with cats (P = 0.013) or soil (P = 0.028). It is concluded that seroprevalence of Toxoplasma infection is higher in indigenous pregnant women and related to their living styles. To prevent congenital toxoplasmosis, health education seems required.     

The importance of precise pT diagnosis for prognostic prediction of uterine cervical cancer—a single institutional report at a Japanese comprehensive cancer hospital

We previously reported that the majority of Japanese pathologists misunderstand the International Union against Cancer-pT2 criteria for uterine cervical cancer (UCC). We compared the prognosis of originally diagnosed pT2 (ori-pT) UCC cases at our hospital with reclassified pT2 (re-pT) cases to assess the importance of making a correct pT diagnosis. There were 43 International Federation of Gynecology and Obstetrics (FIGO) II (i.e., cT2) and/or ori-pT2 UCC cases who received surgery without neoadjuvant chemotherapy at Shikoku Cancer Center from 1991 to 2003. The cases (seven ori-pT1 and 36 ori-pT2; 43 cN0 with six pN1) were reclassified as 22 re-pT1 and 21 re-pT2. Fifteen of the 23 ori-pT2a cases (65%) were re-pT1 because their vaginal extension had only been intraepithelial. The difference in the 5-year survival rate (5Y-SR) was not significant between the ori-pT1 and ori-pT2 cases using Fisher's exact test (F test): P = 0.236 > 0.05, whereas 5Y-SR of re-pT1 cases was significantly higher than re-pT2, including pN1 cases and excluding them (F test: P = 0.00164 < 0.01 and P = 0.0108 < 0.05, respectively). The 5Y-SR of ori-pT2-re-pT1 (overdiagnosed pT2) was significantly higher that of ori-pT2-re-pT2 (true pT2) including pN1 cases and excluding them (F test: P = 0.00694 < 0.01 and P = 0.0305 < 0.05, respectively). These results indicated that pT2 of UCC could be frequently misdiagnosed at an institutional level, and that misdiagnosed pT2 might impair the evidence-based medicine of UCC. Multi-institutional assessment of the accuracy of pTNM is recommended, because it is not likely that this is an endemic problem to our hospital.     

LYVE-1 upregulation and lymphatic invasion correlate with adverse prognostic factors and lymph node metastasis in neuroblastoma

Neuroblastoma (NB) accounts for 15% of all childhood cancer deaths. The majority of patients have widespread lymphatic and/or haematogenous metastases at diagnosis, but lymphangiogenesis has not been well documented. Sixty-seven NBs were immunostained for the lymphatic endothelial marker, LYVE-1, and the lymphatic density (LD) and lymphatic invasion (LI), were counted in LYVE-1-expressing lymphatics. LYVE-1-stained lymphatic vessels and LI were present in 26/67 (39%) and 14/67 (21%) of the NBs, respectively. Central LD (CLD) and LI were higher in NBs from stage 4 (p = 0.012, p = 0.004, respectively), high-risk group (p = 0.030, p = 0.002), NBs with high mitosis karyorrhexis index (MKI) (p = 0.011, p = 0.005), unfavourable histology group (p = 0.040, p = 0.017) and distant lymph node metastasis (LNM) (p < 0.001 for each). Marginal LD (MLD) was higher in patients with LNM (p < 0.001). CLD and MLD correlated with LI (p < 0.001 each). Total LYVE-1 protein levels, quantified by a sensitive enzyme-linked immunosorbent assay (n = 55), were also higher in NBs from patients with stage 4 disease (p = 0.046), high-risk group (p = 0.028), MYCN-amplified NBs (p = 0.034) and LNM (p = 0.038). Kaplan–Meier analysis showed that the presence of CLD was associated with both worse OS at 5 years (77% [95% CI: 62–87%] versus 60% [95% CI: 32–80%], p = 0.062) and EFS (74% [95% CI: 58–85%] versus 43% [95% CI: 15–69%], p = 0.070) and LI with OS (71% [95% CI: 57–81%] versus 56% [95% CI: 26–78%], p = 0.055). Significant upregulation of LYVE-1 and the presence of LI in patients with stage 4 and high-risk disease, MYCN-amplification and LNM suggests that LYVE-1 may have value as predictors of outcome.     

High expression of phosphorylated 4E-binding protein 1 is an adverse prognostic factor in esophageal squamous cell carcinoma

Cell signaling pathways play important roles in oncogenesis. Among a large number of signaling regulators in different pathways, 4E-binding protein 1 (4E-BP1) was found to be a key factor, which converges several oncogenic signals, phosphorylates the molecules, and drives the downstream proliferative signals. Recent studies showed that high expression of phosphorylated 4E-BP-1 (p-4E-BP1) is associated with poor prognosis, tumor progression, or nodal metastasis in different human cancers, but its prognostic significance in esophageal cancer remains undefined. In this study, we investigated the expression levels of p-4E-BP1 with two different phosphorylation sites Thr^37/46 and Thr⁷⁰ by immunohistochemistry and their prognostic significance in 78 cases of surgically resected esophageal squamous cell carcinoma (SCC) for the first time. We found no correlation of p-4E-BP1 expression with age, gender, preoperative concurrent chemoradiotherapy, tumor grade, pT classification, pN, pM, or pStage. Multivariate Cox regression analysis showed that high expression of p-4E-BP-1 Thr^37/46 was an independent adverse prognostic factor, with a hazard ratio of 1.73 (95% confidence interval = 1.03–2.90) and a p value of 0.038. Stratifying the patients with other prognostic factors, we found that the effect of p-4E-BP1 Thr^37/46 on survival was significant only in patients with relatively early stage disease (pT1/pT2, pN0, or pStage I/II; p = 0.0047, 0.012, and 0.011, respectively). Our data suggest that assessment of p-4E-BP1 expression could identify a subpopulation of earlier stage esophageal SCC patients with poor prognosis. These patients could be possible candidates for future studies on more aggressive treatment or target therapy.     

Neuromuscular adaptation during prolonged strength training, detraining and re-strength-training in middle-aged and elderly people

Effects of a 24-week strength training performed twice weekly (24 ST) (combined with explosive exercises) followed by either a 3-week detraining (3 DT) and a 21-week re-strength-training (21 RST) (experiment A) or by a 24-week detraining (24 DT) (experiment B) on neural activation of the agonist and antagonist leg extensors, muscle cross-sectional area (CSA) of the quadriceps femoris, maximal isometric and one repetition maximum (1-RM) strength and jumping (J) and walking (W) performances were examined. A group of middle-aged (M, 37–44 years, n=12) and elderly (E, 62–77, n=10) and another group of M (35–45, n=7) and E (63–78, n=7) served as subjects. In experiment A, the 1-RM increased substantially during 24 ST in M (27%, P < 0.001) and E (29%, P < 0.001) and in experiment B in M (29%, P < 0.001) and E (23%, P < 0.01). During 21 RST the 1-RM was increased by 5% at week 48 (P < 0.01) in M and 3% at week 41 in E (n.s., but P < 0.05 at week 34). In experiment A the integrated electromyogram (IEMG) of the vastus muscles in the 1-RM increased during 24 ST in both M (P < 0.05) and E (P < 0.001) and during 21 RST in M for the right (P < 0.05) and in E for both legs (P < 0.05). The biceps femoris co-activation during the 1-RM leg extension decreased during the first 8-week training in M (from 29 ± 5% to 25 ± 3%, n.s.) and especially in E (from 41 ± 11% to 32 ± 9%, P < 0.05). The CSA increased by 7% in M (P < 0.05) and by 7% in E (P < 0.001), and by 7% (n.s.) in M and by 3% in E (n.s.) during 24 ST periods. Increases of 18% (P < 0.001) and 12% (P < 0.05) in M and 22% (P < 0.001) and 26% (P < 0.05) in E occurred in J. W speed increased (P < 0.05) in both age groups. The only decrease during 3 DT was in maximal isometric force in M by 6% (P < 0.05) and by 4% (n.s.) in E. During 24 DT the CSA decreased in both age groups (P < 0.01), the 1-RM decreased by 6% (P < 0.05) in M and by 4% (P < 0.05) in E and isometric force by 12% (P < 0.001) in M and by 9% (P < 0.05) in E, respectively, while J and W remained unaltered. The strength gains were accompanied by increased maximal voluntary neural activation of the agonists in both age groups with reduced antagonist co-activation in the elderly during the initial training phases. Neural adaptation seemed to play a greater role than muscle hypertrophy. Short-term detraining led to only minor changes, while prolonged detraining resulted in muscle atrophy and decreased voluntary strength, but explosive jumping and walking actions in both age groups appeared to remain elevated for quite a long time by compensatory types of physical activities when performed on a regular basis. Accepted: 2 May 2000     

CD151 expression can predict cancer progression in clear cell renal cell carcinoma

Yoo S H, Lee K, Chae J Y & Moon K C
(2011) Histopathology  58 , 191–197
CD151 expression can predict cancer progression in clear cell renal cell carcinoma Aims: CD151 is known to be implicated in cancer progression and metastasis. The aim was to evaluate the expression of CD151 in clear cell renal cell carcinoma (CCRCC) and to assess its prognostic significance. Methods and results: The expression of CD151 was evaluated in 489 cases of CCRCC by immunohistochemistry. Immunoreactivity was classified into four categories (minimal, 0–10% positive cells; focal, 10–50% positive cells; diffuse moderate, >50% positive cells with moderate staining intensity; diffuse strong, >50% positive cells with strong staining). To determine the statistical significance of CD151 expression in CCRCC, all cases were divided into two groups based on their CD151 expression level: a CD151‐low group (n = 257; minimal and focal) and a CD151‐high group (n = 232; diffuse). Expression of CD151 was correlated positively with pT, pN, pM categories, pathological tumour–node–metastasis (pTNM) stage, nuclear grade, tumour size and patient’s age. The CD151‐high group had significantly shorter cancer‐specific survival (P < 0.001) and progression‐free survival (P < 0.001) times. Furthermore, multivariate analysis showed that CD151 expression was an independent predictor for tumour progression in patients with CCRCC (P = 0.040). Conclusions: High CD151 expression is associated with advanced stage and high nuclear grade in CCRCC. CD151 is a prognostic marker for tumour progression in CCRCC patients.     

Compliance with recommendations and clinical outcomes for formal and informal infectious disease specialist consultations

The purpose of this study was to compare compliance with recommendations and clinical outcomes between formal and informal infectious disease specialist consultations. Six hundred twenty-seven consecutive adult inpatients who received an infectious disease consultation in a university-affiliated hospital were included. After adjusting for quintile of propensity score, we compared compliance with the consultant’s recommendations and clinical outcomes for 443 (70.7%) and 184 (29.3%) formal and informal consultations. Informal and formal consultations were associated with comparable levels of compliance with recommendations for antimicrobial treatment (86.5% vs 88.9%; adjusted odds ratio [aOR], 0.63; 95% confidence interval, 0.34–1.14; P = 0.13) and diagnostic or monitoring tests (72.6% vs 72.0%; aOR, 0.91 [0.53–1.57]; P = 0.73). The rates of early clinical improvement (58.2% vs 58.6%; aOR, 1.11 [0.70–1.74]; P = 0.66), subsequent consultation (34.2% vs 36.3%; aOR, 0.80 [0.53–1.21]; P = 0.29), in-hospital mortality (4.9% vs 8.4%; aOR, 0.55 [0.24–1.24]; P = 0.15), and the median length of stay (23 vs 20 days; aOR of discharge, 0.90 [0.74–1.10]; P = 0.30) did not differ depending on the type of consultation. This study provides observational evidence that informal consultations result in levels of compliance with recommendations comparable to formal consultations, without compromising patient safety. Further study is needed to refine the criteria for requesting or providing informal rather than formal consultations.     

Determinants for the Development of Oropharyngeal Colonization or Infection by Fluconazole-Resistant Candida Strains in HIV-Infected Patients

 A point prevalence study to document oral yeast carriage was undertaken. Risk factors for the development of oropharyngeal colonization or infection by fluconazole-resistant Candida strains in HIV-infected patients were investigated with a case-control design. Cases included all patients with fluconazole-resistant strains (MIC≥64 μg/ml), and controls were those with susceptible (MIC≤8 μg/ml) or susceptible-dependent-upon-dose (MIC 16–32 μg/ml) strains. One hundred sixty-eight Candida strains were isolated from 153 (88%) patients, 28 (16%) of whom had oropharyngeal candidiasis. Overall, 19 (12%) of the patients harbored at least one resistant organism (MIC≥64 μg/ml). Among patients with resistant strains, tuberculosis (P<0.001), esophageal candidiasis (P=0.001), clinical thrush (P<0.001), and a CD4+ cell count <200/mm³ (P=0.03) were more frequent. These patients had also been treated more commonly with antituberculous drugs (adjusted odds ratio [OR] 6.13; 95% confidence interval [CI] 2.11–17.80), ciprofloxacin (OR 6.0; 95% CI 1.23–29.26), fluconazole (OR 4.59; 95% CI 1.55–13.52), and steroids (OR 4.13; 95% CI 1.11–15.39). Multivariate analysis showed that the determinants for fluconazole resistance were therapy with antituberculous drugs (OR 3.61; 95% CI 1.08–12.07;P=0.03) and one of the following: previous tuberculosis (OR 3.53; 95% CI 1.08–14.57;P=0.03) or fluconazole exposure (OR 3.41; 95% CI 1.10–10.54). Findings from this study indicate that treatment with antituberculous drugs, previous tuberculosis, and fluconazole exposure are the strongest determinants for development of oropharyngeal colonization or infection by fluconazole-resistant Candida strains in HIV-infected patients.     

Autoimmune pancreatitis-related diabetes: quantitative analysis of endocrine islet cells and inflammatory infiltrate

In autoimmune pancreatitis (AIP), mechanism(s) of paradoxical glycemic control improvement (GCI) often occurring after pancreatic resection and steroid therapy are not fully elucidated. Using image quantitation, AIP cases (n = 10) with pre- and post-surgical glucose values were compared with chronic pancreatitis (CP) and normal pancreas (NP) regarding percent chromogranin immunohistochemistry (IHC) positivity as a surrogate marker of endocrine endowment; intra-islet T and B lymphocyte and plasma cell enumeration with CD3, CD20, and IgG4 IHC; and CD34 IHC islet vascularity quantitation. Postsurgical GCI, noted in 8/10 (80%) AIP cases, approached statistical significance (P = 0.07) compared to CP. Endocrine endowment reduction, noted by a lower percent of chromogranin + pancreatic parenchyma, was seen in AIP (4.54%) and CP (3.20%) compared to NP (7.95%); only the CP decrease was statistically significant (P = 0.02) since AIP often had ductular endocrine neogenesis. Regression suggested an inverse correlation between endocrine endowment and GCI in AIP (R = 0.62, P = 0.06). AIP islets were smaller and disrupted by inflammatory cell infiltration. Compared to CP, AIP islets had higher CD3 + and CD20 + cell densities. IgG4 + plasma cells were often present at a high density in AIP but typically preserved the islets. Intra-islet CD34 staining showed a lower average vascularity in AIP compared to NP (P = 0.05). This study reaffirms postsurgical GCI in AIP. Prominent intra-islet inflammation and decreased vascularity in AIP may contribute to diabetogenic effects. Endocrine cell neogenesis and relative islet preservation despite islet inflammatory infiltration may explain the paradoxical GCI in AIP.     

Aurora-A/STK-15 is a predictive factor for <Emphasis Type="Italic">recurrent</Emphasis> behaviour in non-invasive bladder carcinoma: a study of 128 cases of non-invasive neoplasms

Aurora-A, a member of serine/threonine kinase, is implied in mitosis and centrosome maturation. Increasing levels of Aurora-A have been shown to be present in several malignancies and especially in bladder cancer. No immunohistochemical marker has shown to be able to predict the clinical outcome of patients with superficial bladder cancer, except MIB-1, as a predictive marker of relapse and progression. The aim was to investigate the expression of Aurora-A and MIB-1 in tissue micro arrays of superficial bladder cancer representative of pTa papillary urothelial neoplasm with different degrees of aggressiveness (low malignant potential [PUNLMP], non-invasive papillary urothelial carcinoma low grade [NILGC], non-invasive papillary urothelial carcinoma high grade [NIHGC] and carcinoma in situ). We analysed predictive values of both markers, their specificity and sensitivity in tumor recurrence. Aurora-A was a sensitive marker to predict tumor recurrence especially for pTa (PUNLMP, NILGC; PUNLMP p < 0.001, NILGC p < 0.001) with statistical significant correlation between immunohistochemical staining and clinical outcome. MIB-1 expression displayed statistical difference p = 0.002 in the PUNLMP group and p = 0.03 in the NILGC group. Aurora-A is a more sensitive marker than MIB-1 to predict relapse in pTa bladder neoplasias. The combination of both markers seems to have a very powerful predictive value of recurrence (p < 0.001).