Long non-coding RNA LINC00346 regulates proliferation and apoptosis by targeting miR-128-3p/SZRD1 axis in glioma.

OBJECTIVE: Long non-coding RNAs (lncRNAs) participate in multiple processes of malignant tumors, including glioma. In this study, we aimed to explore the effect of LINC00346 on glioma and its underlying mechanism. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were used to analyze the expression patterns and survival risk of LINC00346, miR-128-3p and SUZ RNA binding domain containing 1 (SZRD1) in glioma tissues. The binding sites were predicted by bioinformatic databases, and then, validated by Dual-Luciferase assay and RNA immunoprecipitation (RIP). qRT-PCR and Western blot were performed to evaluate the gene expression levels. CellTiter-Glo® and colony formation assays were used to detect the proliferation of glioma cells. Flow cytometric analysis was used to evaluate the apoptosis of glioma cells. The xenograft models were established to investigate the impact of LINC00346 on tumor growth in vivo. RESULTS: We found that both LINC00346 and SZRD1 expression were negatively related to the poor overall survival rate in glioma patients. However, miR-128-3p showed the opposite effect of survival outcomes. LINC00346 knockdown remarkably restrained cell proliferation both in vitro and in vivo, as well as inducing apoptosis by acting as a molecular sponge of miR-128-3p. Moreover, miR-128-3p bound to SZRD1 3'-UTR in a sequence-specific manner. In addition, LINC00346 knockdown significantly inhibited the expression of SZRD1 and the inhibition could be reversed by miR-128-3p mimics. Furthermore, cell proliferation and apoptosis affected by LINC00346 were partially rescued by modulating miR-128-3p or SZRD1 expression. CONCLUSIONS: LINC00346/miR-128-3p/SZRD1 axis played a crucial role in modulating the malignant progression of glioma, which may serve as a prognostic indicator and a probable therapeutic target for glioma.

[Targeted-knockdown of Yes-associated protein inhibits the Warburg effect and the invasion of laryngeal cancer cells].

Objective: To investigate the migration and invasion behaviors of Hep-2 after the targeted knockdown of yes-associated protein (YAP). Methods: Hep-2 cells were knock-downed for YAP by shRNA as YAP-shRNA group, Hep-2 treated with non-specific shRNA as YAP-NC group, and Hep-2 with no treatment as control. Glucose uptake and lactate production in the cells were examined to assess Warburg effect. The migration and invasion behaviors of cells in three groups were observed. The expressions of vimentin and E-cadherin were detected by RT-PCR and Western Blot. The statistical software GraphPad Prism 7.0 was used to analyze significance of data. Two tailed Student' s t-tests was used to determine significance when only two groups were compared. P values of less than 0.05 was considered statistically significant. Results: Downregulation of YAP led to a obvious decrease in glucose uptake [(18.51±1.72)%] and lactate production [103.40±8.32] in Hep-2 cells compared with control [(41.20±1.11)% and 743.69±19.49, t=19.20 and 52.33, respectively, both P<0.01] and YAP-NC group [(39.60±0.78)% and 705.22±17.20, t=19.34 and 54.56, respectively, both P<0.01]. Compared with the control group (78.32±4.04) and YAP-NC group (77.28±3.11), the scratch healing ability of Hep-2 cells was significantly decreased in YAP-shRNA group (44.71±4.68). The P value was less than 0.01 (t=9.42 and 10.04). The number of cells with YAP-shRNA (33.30±4.19) passing through compartments was remarkable fewer than the control group (133.71±6.72) and YAP-NC group (126.32±4.21). The P value was less than 0.01 (t=21.96 and 27.13). The expression of E-cadherin protein in cells of YAP-shRNA group (6.16±0.11) was up-regulated compared with control (0.97±0.10, t=35.70, P<0.01) and YAP-NC group (1.13±0.09, t=36.28, P<0.01), while the expression of vimentin protein in cells of YAP-shRNA group (1.08±0.09) was down-regulated compared with control (5.67±0.12, t=29.91, P<0.01) and YAP-NC group (5.51±0.12, t=29.04, P<0.01). Conclusions: The down-regulation of YAP in Hep-2 inhibits the migration and invasion of cells via suppressing Warburg and EMT program.

A novel bioprinting method and system for forming hybrid tissue engineering constructs.

Three dimensional (3D) bioprinting is a promising approach to form tissue engineering constructs (TECs) via positioning biomaterials, growth factors, and cells with controlled spatial distribution due to its layer-by-layer manufacturing nature. Hybrid TECs composed of relatively rigid porous scaffolds for structural and mechanical integrity and soft hydrogels for cell- and growth factor-loading have a tremendous potential to tissue regeneration under mechanical loading. However, despite excessive progress in the field, the current 3D bioprinting techniques and systems fall short in integration of such soft and rigid multifunctional components. Here we present a novel 3D hybrid bioprinting technology (Hybprinter) and its capability enabling integration of soft and rigid components for TECs. Hybprinter employs digital light processing-based stereolithography (DLP-SLA) and molten material extrusion techniques for soft and rigid materials, respectively. In this study, poly-ethylene glycol diacrylate (PEGDA) and poly-(ε-caprolactone) (PCL) were used as a model material for soft hydrogel and rigid scaffold, respectively. It was shown that geometrical accuracy, swelling ratio and mechanical properties of the hydrogel component can be tailored by DLP-SLA module. We have demonstrated the printability of variety of complex hybrid construct designs using Hybprinter technology and characterized the mechanical properties and functionality of such constructs. The compressive mechanical stiffness of a hybrid construct (90% hydrogel) was significantly higher than hydrogel itself (∼6 MPa versus 100 kPa). In addition, viability of cells incorporated within the bioprinted hybrid constructs was determined approximately 90%. Furthermore, a functionality of a hybrid construct composed of porous scaffold with an embedded hydrogel conduit was characterized for vascularized tissue engineering applications. High material diffusion and high cell viability in about 2.5 mm distance surrounding the conduit indicated that culture media effectively diffused through the conduit and fed the cells. The results suggest that the developed technology is potent to form functional TECs composed of rigid and soft biomaterials.

Antibody-directed coupling of endoglin and MMP-14 is a key mechanism for endoglin shedding and deregulation of TGF-ß signaling.

Endoglin is a transforming growth factor ß (TGF-ß) coreceptor that serves as a prognostic, diagnostic and therapeutic vascular target in human cancer. A number of endoglin ectodomain-targeting antibodies (Abs) can effectively suppress both normal and tumor-associated angiogenesis, but their molecular actions remain poorly characterized. Here we define a key mechanism for TRACON105 (TRC105), a humanized monoclonal Ab in clinical trials for treatment of advanced or metastatic tumors. TRC105, along with several other endoglin Abs tested, enhance endoglin shedding through direct coupling of endoglin and the membrane-type 1 matrix metalloproteinase (MMP)-14 at the cell surface to release the antiangiogenic factor, soluble endoglin (sEng). In addition to this coupling process, endoglin shedding is further amplified by increased MMP-14 expression that requires TRC105 concentration-dependent c-Jun N-terminal kinase (JNK) activation. There were also notable counterbalancing effects on canonical Smad signaling in which TRC105 abrogated both the steady-state and TGF-ß-induced Smad1/5/8 activation while augmenting Smad2/3 activation. Interestingly, TRC105-induced sEng and aberrant Smad signaling resulted in an excessive migratory response through enhanced stress fiber formation and disruption of endothelial cell-cell junctions. Collectively, our study defines endoglin shedding and deregulated TGF-ß signaling during migration as major mechanisms by which TRC105 inhibits angiogenesis.

A high resolution genomic portrait of bladder cancer: correlation between genomic aberrations and the DNA damage response.

One major challenge in cancer research is to understand the complex interplay between the DNA damage response (DDR), genomic integrity, and tumor development. To address these issues, we analyzed 43 bladder tumor genomes from 22 patients using single nucleotide polymorphism (SNP) arrays, and tissue expression of multiple DDR proteins, including Timeless and its interaction partner Tipin. The SNP profiles confirmed and extended known copy number alterations (CNAs) at high resolution, showed clustering of CNAs at nine common fragile sites, and revealed that most metachronous tumors were clonally related. The occurrence of many novel uniparental disomy regions (UPDs) was of potential functional importance in some tumors because UPDs spanned mutated FGFR3 and PIK3CA alleles, and also homozygous deletion of the CDKN2A tumor suppressor locus. The DDR signaling as evaluated by phospho-epitope-specific antibodies against Ser139-phosphorylated H2A histone family member X (γH2AX), ataxia telangiectasia mutated (ATM), and ATM- and Rad3-related (ATR) was commonly activated in tumors with both moderate and high extent of accumulated genomic aberrations, the latter tumors showing a more frequent loss of ATM expression. Strikingly, the tumor genomes exhibiting the most complex alterations were associated with a high Ki67-proliferation index, abundant Timeless but not Tipin expression, aberrant p53 expression, and homozygous CDKN2A deletions. Of clinical relevance, evaluation of a tissue microarray (TMA; n=319) showed that abundant Timeless expression was associated with risk of progression to muscle-invasive disease (P<0.0005; hazard ratio, 2.4; 95% confidence interval, 1.6-3.8) and higher T stage (P<0.05). Univariate analysis confirmed this association (P=0.006) in an independent cohort (n=241) but statistical significance was not reached in a multivariate model. Overall, our results are consistent with DDR activation preceding the accumulation of genomic aberrations. Tumors with extensive genomic rearrangements were associated with inactivation of CDKN2A, excessive proliferation, and robust Timeless expression, the latter also correlating with the risk of disease progression. Moreover, we provide evidence to suggest that UPDs likely contribute to bladder tumorigenesis.

Immunostaining of glutamine synthetase is a sensitive and specific marker for diagnosing focal nodular hyperplasia in needle biopsy.

AIMS: Focal nodular hyperplasia (FNH) has characteristic histological features which may not be seen in needle biopsy specimens. We investigate the diagnostic role of glutamine synthetase (GS) in needle biopsy specimens. METHODS: Sixty-one hepatic tumours were categorised into 20 'definite' FNHs, 13 'probable' FNHs, and 28 cases without specific diagnosis. Needle biopsy specimens of 92 non-tumourous lesions, 25 well-differentiated hepatocellular carcinomas (WDHCCs), and 4 high-grade dysplastic nodules (HGDNs) and resection specimens of 10 macroregenerative nodules were also selected for immunohistochemical stain of GS for comparison. RESULTS: All 20 'definite' FNHs, nine 'probable' FNHs, and five cases without specific diagnosis expressed typical map-like staining pattern of GS. The demographic data of these five cases were similar to those of FNH. All cases of chronic hepatitis B and C, cirrhosis, macroregenerative nodule and peritumourous liver tissue showed normal pericentral/periseptal pattern. Fifteen of 25 WDHCCs and one HGDN showed diffuse pattern. Ten WDHCCs and two HGDNs showed negative staining. One HGDN showed mosaic pattern. CONCLUSIONS: Immunohistochemical staining of GS increases the diagnostic sensitivity of FNH in needle biopsy, especially in those without typical morphology. It also helps in differentiating FNH from other tumourous and non-tumourous lesions.

Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma.

Perivascular epithelioid cell tumours (PEComas) are a family of tumours including classic angiomyolipoma, lymphangioleiomyomatosis, and clear epithelioid cell tumours reported under a variety of names such as epithelioid angiomyolipoma, pulmonary and extrapulmonary clear cell sugar tumour, and PEComa. Our previous comparative genomic hybridization study of PEComas demonstrated recurrent chromosomal aberrations including deletions on chromosome 16p, where the TSC2 gene is located. In this study, we focused on the alteration of chromosome 16p, including TSC2. We collected ten sporadic and two tuberous sclerosis complex-associated PEComas, as well as 14 sporadic classic hepatic and renal angiomyolipomas (AMLs) as controls. We used 16 microsatellite markers distributed along chromosome 16p to test for allelic imbalances on chromosome 16p and at TSC2, and two markers for TSC1. Furthermore, we carried out immunohistochemical staining for phospho-p706K, phospho-AKT, and phospho-S6 to evaluate the effect of TSC2 alterations on the mTOR signalling pathway. Loss of heterozygosity (LOH) was found in 11 PEComas and involved the region of the TSC2 locus in seven. Six classic angiomyolipomas had allelic changes at chromosome 16p. Microsatellite instability was detected in two PEComas. The incidence of genetic aberrations was significantly higher in the PEComa group. Only one PEComa showed LOH at the TSC1 locus. Eleven PEComas and 13 AMLs revealed elevated phospho-p70S6K accompanied by reduced phospho-AKT. Five PEComas and eight classic angiomyolipomas were positive for phospho-S6. The phosphorylation profile indicates functional activation of the mTOR pathway through a disrupted TSC1/2 complex. Our observations of frequent deletion of TSC2 and the mTOR signalling pathway provide evidence that the oncogenetic lineage of PEComa, as a distinct TSC2-linked neoplasm, is similar to that of angiomyolipoma.

The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases.

AIMS: To demonstrate the diagnostic utility of MOC31, BerEP4, renal cell carcinoma marker (RCC Ma) and CD10 in the classification of RCC and renal oncocytoma, based upon a comprehensive immunohistochemical analysis. METHODS AND RESULTS: Immunohistochemistry was performed on 328 samples consisting of 256 clear cell/conventional, 27 papillary, 28 chromophobe, five collecting duct, five unclassified RCCs and seven renal oncocytomas using antibodies MOC31, BerEP4 and antibodies against cytokeratins (KL-1, CAM5.2, 34betaE12, cytokeratin 7), RCC Ma, epithelial membrane antigen, E-cadherin, CD10, CD15 and vimentin. Multivariate analysis showed that MOC31, BerEP4, RCC Ma and CD10 have discriminatory value. MOC31 and BerEP4 chiefly labelled distal tubules of normal kidney while RCC Ma and CD10 labelled the proximal tubules. Twenty-three chromophobe RCCs (82%) were reactive for MOC31, while only four clear cell RCCs and three papillary RCCs were positive for this marker. Clear cell RCCs were characterized by a high positive rate for CD10 (82%) and a low positive rate for BerEP4 (27%). Papillary RCCs frequently coexpressed RCC Ma and BerEP4 (51%). All renal oncocytomas were negative for MOC31 and CD10. CONCLUSIONS: MOC31 has diagnostic merit in discerning chromophobe RCC. The CD10+/BerEP4- profile and RCC Ma+/BerEP4+ profile achieve moderate sensitivity and good specificity for clear cell RCC and papillary RCC, respectively. The non-reactivity for both MOC31 and CD10 is helpful in distinguishing renal oncocytoma from RCC. When properly selected, antibodies have immunohistochemical diagnostic utility for the classification of renal cortical epithelial tumours.

Expression of apoptosis-related markers and HER-2/neu in thymic epithelial tumours.

AIMS: To correlate the expression of a series of apoptotic and oncogene markers (including p53, Bcl-2, BAX, Bcl-XL, p21WAF,1/CIP1, cyclin D1, HER-2/neu) in thymic epithelial tumours with histological type, stage and resectability and to determine whether the information on HER-2/neu would be valuable in identifying patients who are eligible for anti-HER-2/neu treatment. METHODS AND RESULTS: Immunohistochemical stains were performed on 16 cases of non-neoplastic thymus, 63 thymomas and 17 thymic carcinomas. Fluorescence in-situ hybridization (FISH) for HER2 was performed to validate the gene amplification. Eighteen thymomas were positive for p53 and 14 of them were low-expressors, with positive cells below 10%. All thymic carcinomas revealed over-expression of p53 with positive cells either between 10% and 50% or >50%. The expression of p53 correlated with histological type and stage in thymoma. In both thymoma and thymic carcinoma, there was a statistically significant correlation between p53 status and resectability, with low expressors having a higher likelihood of being resectable. Thymic carcinomas, regardless of the histological subtypes, uniformly expressed Bcl-2, while thymomas showed no or only weak cytoplasmic immunoreactivity. Most thymomas and thymic carcinomas were negative for Bcl-XL, p21WAF,1/CIP1 and cyclin D1. The expression of BAX was inconsistent among different histological types. Nine thymic carcinomas revealed membranous positivity for HER-2/neu, but no HER2 gene amplification could be demonstrated by FISH in any of the cases. CONCLUSIONS: p53 and Bcl-2 are more implicated in the development of thymic carcinoma than thymoma. The higher level of p53 expression and the strong immunopositive pattern of Bcl-2 in thymic carcinomas have potential value in the differential diagnosis and prediction of aggressiveness and resectability. On account of the absence of HER2 amplification, patients would probably not benefit from anti-HER-2/neu treatment.

Influence of 3D-CRT pelvic irradiation on outcome in prostate cancer treated with external beam radiotherapy.

PURPOSE: The role of pelvic irradiation (PRT) in the treatment of prostate cancer remains unclear. We reviewed our institution's experience with three-dimensional conformal external beam radiotherapy (3D-CRT) during the prostate-specific antigen era to determine the influence of PRT on the risk of biochemical recurrence in patients who have a predicted risk of lymph node involvement. METHODS AND MATERIALS: Between March 1985 and January 2001, 1832 patients with clinically localized prostate cancer were treated with definitive 3D-CRT. All treatments involved CT planning to ensure coverage of the intended targets. Treatment consisted of prostate-only treatment, prostate and seminal vesicle treatment, or PRT of lymph nodes at risk followed by a boost. To create relatively homogenous analysis groups, each patient's percentage of risk of lymph node (%rLN) involvement was assigned by matching the patient's T stage, Gleason score, and initial prostate-specific antigen level to the appropriate value as described in the updated Partin tables. Three categories of %rLN involvement were defined: low, 0-5%; intermediate, >5-15%; and high, >15%. Biochemical recurrence was defined as the first occurrence of either the American Society for Therapeutic Radiology and Oncology consensus definition of prostate-specific antigen failure or the initiation of salvage hormonal therapy for any reason. RESULTS: The risk status (%rLN) could be determined for 709 low-risk, 263 intermediate-risk, and 309 high-risk patients. The actuarial freedom from biochemical recurrence (bNED) and the log-rank test for the similarity of the control and treatment survival functions are reported for each risk group. Multivariate analysis demonstrated a statistically significant benefit for the entire population treated with PRT, with a relative risk reduction of 0.72 (95% confidence interval 0.54-0.97). Although the multivariate analysis could not determine the patient population that would most benefit from PRT, the beneficial effect appeared to be most pronounced within the intermediate-risk group. Univariate analysis revealed that the intermediate-risk patients treated with PRT had an improved 2-year bNED rate, 90.1% vs. 80.6% (p = 0.02), and both low-risk and high-risk patients treated with PRT had statistically similar 2-year bNED rates compared with those who did not receive it. CONCLUSION: Pelvic 3D-CRT appears to improve bNED in prostate cancer patients. Additional studies are needed to elucidate the %rLN population for which this treatment should be recommended.

Thymoma is associated with an increased risk of second malignancy.

BACKGROUND: An association between thymoma and second malignancy has been suggested but has not been validated. Whether the relation is due to treatment or to other thymoma-associated conditions is unclear. METHODS: The authors studied 192 consecutive patients with thymoma and compared the incidence of second malignancies with those of 206 patients who underwent thymectomy for nonthymomatous conditions and 1426 patients with nasopharyngeal carcinoma (NPC). Detailed clinicopathologic features of thymoma patients with second malignancies were described. RESULTS: Additional malignancies were detected in 15 of 192 patients (8%) during their clinical courses. The risk for those patients was significantly greater compared with the risk for patients with nonthymomatous conditions (adjusted odds ratio [OR], 3.81; 95% confidential intervals [95%CI], 1.05-13.81; P = 0.042) and patients with NPC (adjusted OR, 4.89; 95%CI, 2.26-10.53; P < 0.0001) after adjustment for age, gender, length of follow-up, myasthenia gravis, and radiation therapy. The occurrence of second malignancies did not correlate with histologic type or stage of thymoma, radiation therapy, or myasthenia gravis. CONCLUSIONS: Thymoma is associated with an increased risk of second malignancy. The association cannot be attributed to the effect of thymectomy or radiation therapy. Patients with thymoma, even if it is benign, should be followed regularly to facilitate the early detection of other malignancies.

High failure rate using allograft fascia lata in pubovaginal sling surgery for female stress urinary incontinence.

OBJECTIVES: To present our unfavorable experiences using allograft fascia lata. Allograft fascia lata is an attractive sling material providing less pain, a shorter operation time, and a reported effectiveness equal to autologous fascia. METHODS: A total of 18 women (mean age 51.7 years, range 37 to 76) underwent pubovaginal sling surgery for stress urinary incontinence between March 1999 and July 1999 and were enrolled in this study. Solvent dehydrated gamma-irradiated human fascia lata with a size of 7 x 2 cm was used as the sling. The results were collected with a questionnaire survey. RESULTS: All patients were followed up for a mean of 9.2 months (range 6.9 to 11.6). Thirteen patients considered the surgery successful or to have provided improvement, with a mean of 82.5% (range 50% to 100%) subjective improvement. Five patients (27.8%) had significant failure with full recurrence of incontinence within 3 to 6 months. CONCLUSIONS: Solvent dehydrated gamma-irradiated allograft fascia is not reliable in pubovaginal sling surgery. The high failure rates within a short period prohibit its use in the operative management of stress urinary incontinence.

Real-time dynamic telepathology through the Internet: evaluation of a new and economic technology at Taipei Veterans General Hospital.

BACKGROUND: Computer-aided, digitalized telepathology was introduced about 10 years ago and is gaining acceptance as a mode of providing pathology to remote site. The usefulness of telepathology for remote diagnosis of histology, cytology and frozen section has been evaluated in USA, Europe and Japan. In Taiwan, the use of telepathology for pathological diagnosis is still rare. In order to evaluate the potential use of this technique, we undertook the study using commercialized and low-cost microscopy, personal computer and software on routine biopsy material. METHODS: Sixty prostatic sextant transrectal needle biopsies, including 30 cases of adenocarcinoma and 30 cases of benign lesions, were retrieved retrospectively. The real-time dynamic images were transmitted to the remote site via internet and reviewed by a senior uropathologist who was unaware of the diagnosis. The diagnoses made at the remote site were correlated to the final diagnoses of the cases. RESULTS: All malignant specimens (30/30) were correctly diagnosed by this method. Only one benign case (1/31) of nonspecific granulomatous prostatitis was misdiagnosed as poorly differentiated carcinoma. CONCLUSIONS: Our results show that this method is a good way for teleconsultation. Further studies on other types of specimen worth encouragement for both intra- and inter-institutional consultation.

Expression of cyclooxygenase-2 in prostate adenocarcinoma and benign prostatic hyperplasia.

Elevated expression of cyclo-oxygenase (COX)-2 has been found in several human cancers, including prostate adenocarcinoma. To evaluate the potential prognostic role of COX-2 in prostate cancer, we assessed the expression of COX-2 in benign prostatic hyperplasia (BPH) and prostate cancer samples employing immunohistochemistry. COX-2 was over-expressed in 15 out of 18 (83%) prostate cancer samples whereas it was detected in only 22% (4 of 18) paired benign tissues. The intensity of immunostaining correlated with the tumor grading. In addition, COX-2 was expressed in 7 of the 22 (32%) BPH samples examined. The significance a COX-2 expression in the BPH samples is not known at present. This data suggest that COX-2 is over-expressed in prostate cancer and COX-2 inhibitors may be useful in combination chemotherapy or chemoprevention for prostate cancer.

Comparative analysis of sampling methods for grossing radical prostatectomy specimens performed for nonpalpable (stage T1c) prostatic adenocarcinoma.

Scant data are available comparing sampling methods of radical prostatectomy specimens performed for clinical stage T1c (nonpalpable) cancer. Seventy-eight stage T1c radical prostatectomies that had 1 or more of the following adverse pathologic findings-Gleason score > or = 7, positive margins, and extraprostatic extension-were compared using 10 different sampling techniques. Of the 78 entirely submitted cases, 52 had Gleason score > or = 7, 14 had positive margins, and 54 had extraprostatic extension (mean 34 slides). Of the partial sampling methods, we favor the following two methods. The first is submitting every posterior section plus 1 midanterior section from right and left sides; if either of these anterior sections show sizeable tumor, all ipsilateral anterior slides are examined. This method detects 98% of tumors with Gleason score > or = 7, 100% of positive margins, and 96% of cases with extraprostatic extension (mean 27 slides). The second method is to use the above method but restrict it to sections ipsilateral to the previous positive needle biopsy. This method detects 92% of tumors with Gleason score > or = 7, 93% of positive margins, and 85% of cases with extraprostatic extension (mean 17 slides). Partial sampling can detect important prognostic parameters. By balancing the extra expense and time involved to process and examine additional sections with the risk of missing important prognostic parameters, pathologists can decide which sampling method to use.

Spindle cell and mixed spindle/lymphocytic thymomas: an integrated clinicopathologic and immunohistochemical study of 81 cases.

Forty-three cases of spindle cell thymoma (medullary, WHO type A) and 38 cases of mixed spindle/lymphocytic thymoma (WHO type AB) were studied for their clinicopathologic and immunohistochemical characteristics. Three histologic patterns of spindle cell thymoma were observed: short-spindled (57%), long-spindled (31%), and micronodular (12%). The short-spindled variant was composed of oval to short spindle cells commonly arranged in a hemangiopericytic or microcystic pattern. The long-spindled variant chiefly consisted of fibroblast-like epithelial cells mimicking fibrohistiocytic neoplasms. The micronodular variant was characterized by small nests of short spindle cells dispersed among a lymphoid stroma with frequent germinal centers. All kinds of spindle cell could be admixed with lymphocyte-rich "cortex"-like areas to constitute mixed spindle/lymphocytic thymomas. Immunohistochemically, the epithelial cells in up to 70% of the short-spindled and long-spindled variants of spindle cell thymoma and 90% of mixed spindle/lymphocytic thymomas were positive for CD20, whereas the epithelial cells in all micronodular spindle cell thymomas were negative. All of the spindle cell thymomas and most of the mixed spindle/lymphocytic thymomas in this study were found in stages I and II. Follow up of the patients did not disclose relapse or mortality directly resulting from the tumors. However, the prognosis of stage I and II spindle cell and mixed spindle/lymphocytic thymomas did not significantly differ from those of stage I and II thymomas of other types by a stage-matched survival analysis. Our data showed that spindle cell and mixed spindle/lymphocytic thymomas are distinctive in histologic pattern and immunohistochemical profile. When interpreted within the context of staging, spindle cell and mixed spindle/lymphocytic thymomas presenting in stages I and II most likely behave in an indolent fashion.

Tubulocystic clear cell adenocarcinoma arising within the prostate.

Neoplasms resembling ovarian common epithelial-type tumors, including clear cell adenocarcinomas, rarely occur in the lower urinary tract of men. When they do, they develop in the urethra or urinary bladder. We report a case of such a tumor arising within the prostate of a 47-year-old man. The tumor was a cystic mass in the left posterolateral region of the prostate. Histologically, the tumor was chiefly composed of tubulocystic and papillary glands lined by glycogen-rich, cuboidal or hobnail cells with clear to eosinophilic cytoplasm. The tumor cells were strongly positive for pan-cytokeratin, low molecular weight cytokeratin, and epithelial membrane antigen, and focally positive for high molecular weight keratin. The tumor did not immunohistochemically express prostate-specific antigen (PSA) and prostatic acid phosphatase. Serologically, the patient had increased levels of CA125 instead of PSA. The clinical as well as the pathologic features are consistent with a clear cell adenocarcinoma as seen in the female genital tract rather than a typical prostatic adenocarcinoma.